bluuebunny/crossref_metadata_2025 huggingface dataset:
P4984The functional and coronary anatomic correlates of coronary flow velocity reserve during stress echocardiography
Authors: Ciampi Q , Zagatina A , Cortigiani L , Gaibazzi N , Borguezan Daros C , Zhuravskaya N , Wierzbowska-Drabik K , De Castro E Silva Pretto J L , D'Andrea A , Djordjevic-Dikic A , Simova I , Boshchenko A , Amor M , Merlo P B , Picano E
Published: October 2019

Background

The assessment of coronary flow velocity reserve (CFVR) on left anterior descending coronary artery (LAD) expands the risk stratification potential of stress echocardiography (SE) based on regional wall motion abnormalities (RWMA).

Aim

To assess the feasibility and functional correlates of CFVR.

Methods

In a prospective, observational, multicenter study, we initially screened 3,410 patients (2061, 60%, male; age 63±11 years; ejection fraction, EF=61±9%) with known or suspected coronary artery disease (CAD) and/or heart failure (HF). All patients underwent SE (exercise, n=1288; vasodilator, n=1860; dobutamine, n=262) based on RWMA in 20 accredited laboratories of 8 countries. CFVR was calculated as the stress/rest ratio of diastolic peak flow velocity pulsed-Doppler assessment of LAD flow. We also assessed B-lines (a sign of pulmonary congestion) with lung ultrasound and left ventricular contractile reserve (LVCR) based on Force (systolic blood pressure/end-systolic volume).

Results

The success rate for CFVR on LAD was 3,002/3,410 (feasibility=88%): 1,025/1,288 for exercise (80%), 1,766/1,860 (95%) for vasodilator (dipyridamole, n=1,841 and adenosine= 18) and 211/262 (81%) for dobutamine (p<0.001 vs vasodilator, p=NS vs exercise). Imaging time was <3 min and analysis time <1 min per patient. Reduced (≤2.0) CFVR was found in 896/3,002 (30%) patients. At multivariate logistic regression analysis, age (odds ratio, OR: 1.025, 95% Confidence intervals, CI: 1.015–1.036, p<0.001), diabetes (OR: 2.271, 95% CI: 1.218–4.235, p=0.10), RWMA (OR: 6.550, 95% CI: 4.989–8.599, p<0.01), abnormal LVCR (OR: 3.446, 95% CI: 2.774–4.281, p<0.01) and stress-rest B-lines change (OR: 1.519, 95% CI: 1.174–1.99, p=0.01) were associated with reduced CFVR. In the 1149 patients with coronary angiographic information, a reduced CFVR was present in 103/455 patients (23%) with no CAD, 119/432 (27%) with 1-, 72/167 (43%) with 2-, and 62/95 (65%) with 3-vessel disease (p<0.001 by ANOVA for trend).

Figure 1

Conclusions

CFVR is feasible with all SE protocols. The reduced CFVR is often accompanied by RWMA, abnormal LVCR and pulmonary congestion during stress.
P4992The ceramide-based Coronary Event Risk Test (CERT) predicts cardiovascular mortality in cardiovascular disease patients with type 2 diabetes mellitus as well as in those without diabetes
Authors: Leiherer A , Muendlein A , Saely C H , Laaksonen R , Laaperi M , Vonbank A , Larcher B , Mader A , Baumgartner I , Fraunberger P , Drexel H
Published: October 2019

Background

The recently introduced Coronary Event Risk Test (CERT) is a validated cardiovascular risk predictor that uses circulating ceramide concentrations to allocate patients into one of four risk categories.

Purpose

The purpose of this study was to investigate the power of CERT to predict cardiovascular mortality in patients with established cardiovascular disease (CVD) including patients with type 2 diabetes (T2DM).

Methods

We investigated a total of 1087 patients with established CVD, including 360 patients with T2DM.

At baseline, the prevalence of T2DM increased through CERT categories (29.1, 31.1, 37.4, and 53.4%, respectively, ptrend<0.001). Prospectively, cardiovascular deaths were recorded during a mean follow-up time of 8.1±3.2 years.

Results

A total of 130 cardiovascular deaths occurred. Overall, cardiovascular mortality increased with increasing CERT categories (figure) and was higher in T2DM patients than in those who did not have diabetes (17.7 vs. 9.4%; p<0.001). In Cox regression models, CERT categories predicted cardiovascular mortality in patients with T2DM (unadjusted HR 1.60 [1.28–2.01]; p<0.001; HR adjusted for age, gender, BMI, smoking, LDL cholesterol, HDL cholesterol, hypertension, and statin use 1.65 [1.27–2.15]; p<0.001) and in those without diabetes (unadjusted HR 1.43 [1.10–1.85]; p=0.008 and adjusted HR 1.41 [1.07–1.85]; p=0.015).

Cardiovascular survival of CVD patients

Conclusion

We conclude that CERT predicts cardiovascular mortality in CVD patients with T2DM as well as in those without diabetes.
P5001Acute cardiac fibrogenic response triggered by endotrophin, a type VI collagen signalling molecule
Authors: Reese-Petersen A L , Karsdal M , Genovese F
Published: October 2019

Background/Aim

Accumulation of extracellular matrix (ECM) proteins is the hallmark of cardiac fibrosis, causing stiffening of the ventricular wall, which can lead to heart failure and ultimately death. Many different cell types and growth factors are involved in this process but fibroblasts are the main source of ECM proteins. Here we present results from an in vitro model indicating that endotrophin (ETP), a collagen type VI fragment, activates cardiac fibroblasts and induces fibrogenesis.

Methods

The effect of ETP, transforming growth factor (TGF)-β and platelet-derived growth factor (PDGF)-DD on ECM protein synthesis was assessed in a scar-in-a-jar (SiaJ) cell model using human cardiac fibroblasts isolated from the atrium of an adult healthy donor. Cells were seeded in 48-well plates at a density of 30.000 cells/well and incubated for 24H in Dulbecco's Modified Eagle's medium (DMEM) + 10% fetal bovine serum (FBS). Serum starvation was done by seeding the cells for further 24H in DMEM + 0.4% FBS. Fresh medium was added at day 0 with 37.5/25mg/mL Ficoll 70/400 and 1% ascorbic acid, containing 11.75 nM human recombinant ETP, 0.04 nM TGF-β, 0.39 nM PDGF-DD or a vehicle control. Medium was changed and collected at day 3 and 6. Biomarkers of type I (PRO-C1), III (PRO-C3), VI (PRO-C6) collagens and fibronectin (FBN-C) formation were assessed in the medium by ELISAs developed at Nordic Bioscience.

Results

ETP induced a significant increase in PRO-C1, PRO-C3 and FBN-C (comparable to TGF-β and PDGF-DD) within the first three days of the experiment, compared to the vehicle control. The levels remained significantly increased for PRO-C3 and FBN-C throughout the experiment, and non-significantly elevated for PRO-C1, compared to the vehicle control. PDGF-DD significantly induced synthesis of type VI collagen compared to the vehicle control, while TGF-β induced a small increase in synthesis from day 0–3, after which it seemed to inhibit synthesis.

Conclusion

For the first time, a direct pro-fibrotic effect on fibroblasts induced by ETP has been shown. This novel pathway of activation could play an important role in regulating cardiac fibrosis, and thus prove to be a therapeutic target. This SiaJ model in combination with the investigated biomarkers of ECM formation could be used to further elucidate the mechanisms behind cardiac fibrosis.
P5004Peripheral neuropathy and increased risk of heart failure: a population-based longitudinal cohort study
Authors: Sun Y , Oxnard J , New B J , Mordi I R , Meng W , Tee A , Palmer C N , McCrimmon R , Doney A S , Lang C C
Published: October 2019

Background

One of the main pathophysiological processes thought to be implicated in the development of diabetic cardiomyopathy is a microvascular disease (MiVD) that is prevalent in type 2 diabetes (T2D). However, the role of MiVD in the development of heart failure (HF) is not known. T2D screening programmes identify three types of MiVD – retinopathy, nephropathy and neuropathy. Both retinopathy and nephropathy have been independently associated with the development of incident HF in observational cohort studies. There is less data on peripheral neuropathy and HF outcomes. This study aimed to determine the independent association of diabetic neuropathy with incident HF events in a large longitudinal population cohort of T2D patients with a detailed clinical follow-up that includes available echocardiographic data.

Design

This was a population-based longitudinal cohort study from the Genetics of Diabetes Audit and Research in Tayside Scotland study (GoDARTS) from 1996 to 2016. A total of 9,598 patients with T2D were included with data available on hospital admissions, prescribing and other clinical variables including age, gender, smoking history, duration of T2D, body mass index, systolic blood pressure, glycosylated haemoglobin (HbA1c), triglyceride, total LDL and HDL cholesterol levels. Neuropathy cases were identified using a well-validated record linkage method utilising neuropathic drug prescription records to identify cases of neuropathic pain and to monofilament testing that is used to diagnose neuropathy.

Results

There were 805 HF events. After adjustment for clinical variables, the presence of painful neuropathy related to a 57% increased risk of incident HF (HR 1.57, 95% CI = 1.32–1.89, p<0.001). A similar risk was also observed with diabetic neuropathy identified by monofilament testing with a 52% (HR 1.52, CI = 1.013–1.225, P<0.05) increased risk of incident HF.

Conclusions and relevance

Peripheral neuropathy, a feature of MiVD, may be pathophysiologically associated with the development of HF in patients with T2D and may be a therapeutic target.
P5006Metformin reduces the risk of hospitalization for heart failure in type 2 diabetes patients: a retrospective cohort analysis
Authors: Tseng C H
Published: October 2019

Background

A beneficial effect of metformin on heart failure requires confirmation.

Purpose

To investigate whether metformin might affect the risk of heart failure hospitalization in type 2 diabetes patients.

Methods

Patients with new-onset type 2 diabetes during 1999–2005 were enrolled from the reimbursement database of Taiwan's National Health Insurance and followed until December 31, 2011. Analyses were conducted in a propensity score (PS) matched-pair cohort (42,367 ever users and 42,367 never users) and hazard ratios were estimated by Cox's hazard regression analysis incorporated with the inverse probability of treatment weighting using the PS.

Results

A total of 1,592 never users and 987 ever users were hospitalized for heart failure for the first time during follow-up, with a respective incidence of 843.34 and 499.18 per 100,000 person-years. The overall hazard ratio was 0.588 (95% confidence interval: 0.543–0.637), and the hazard ratios for the first (<29.13 months), second (29.13–61.63 months), and third (>61.63 months) tertiles of cumulative duration were 1.018 (0.914–1.135), 0.575 (0.511–0.647), and 0.340 (0.297–0.390), respectively. Sensitivity analyses conducted in an unmatched cohort before and after excluding patients who received an irregular refill of metformin or who were treated with incretin-based therapies during follow-up consistently supported such a protective effect of metformin on heart failure.

Conclusion

Metformin use is associated with a lower risk of hospitalization for heart failure.

Acknowledgement/Funding

The study was partly supported by the Ministry of Science and Technology (MOST 107-2221-E-002-129-MY3) of Taiwan.
P5015Efficacy of lipid lowering therapy beyond statins to prevent cardiovascular events: A meta-analysis
Authors: Dykun I , Mincu R , Totzeck M , Rassaf T , Mahabadi A A
Published: October 2019

Background

Lipid lowering therapy is a key cornerstone in secondary prevention of patients with coronary artery disease. However, only a minority of patients with statin therapy reach LDL thresholds as suggested by the ESC. Ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors allow for reduction in LDL-cholesterol in addition to statin therapy.

Purpose

To perform a meta-analysis of existing trials, evaluating how lipid lowering therapy beyond statins impacts cardiovascular outcome.

Methods

We performed a systematic search using the Pubmed, Cochrane, SCOPUS, and Web of Science databases for studies, evaluating the impact of an intensified lipid lowering therapy via ezetimibe or PCSK-9 inhibitor in addition to statin therapy compared to statin therapy alone. Manuscript and congress presentations, published until 1st of November 2018, were included. We made our search specific and sensitive using Medical Subject Headings terms and free text and considered studies published in English language. Search terms used were “ezetimibe”, “evolocumab”, “alirocumab”, or “bococizumab” and “cardiovascular events”.

Results

A total of 100,610 patients from 9 randomized controlled trials (IMPROVE-IT, FOURIER, ODYSSEY Outcomes, SIPRE I, SPIRE II, ODYSSEY LONG TERM, OSLER-1 and OSLER-2, HIJ-PROPER) were included. Treatment with ezetimibe or a PCSK-9 inhibitor was associated with a 18% risk reduction in cardiovascular events (OR [95% CI]: 0.82 [0.75–0.89]). Effect sizes were similar for myocardial infarction (0.84 [0.76–0.92]) and even more pronounced for ischemic stroke (0.77 [0.67–0.83]). In contrast, all-cause mortality was not improved by the intensified lipid lowering therapy (0.94 [0.85–1.05]). No relevant heterogeneity and inconsistency between groups was present in all analyses (detailed data not shown). Comparing efficacy of LDL-reduction and relative risk redaction of cardiovascular events, a linear relationship was observed (figure).

Figure 1. Correlation of reduction of LDL-cholesterol at one year with relative risk reduction (95% confidence interval) of cardiovascular events in included trials.

Conclusion

Intensified LDL-lowering therapy with ezetimibe or PCSK-9 inhibitors, in addition to statins, reduces the risk of myocardial infarction and stroke, however, does not impact overall mortality. There is a linear relationship between LDL reduction and cardiovascular risk reduction, confirming the beneficial effects of LDL lowering therapy beyond statins in secondary prevention.
P5022Dual-energy CT was effective to evaluate of microvasculopathy in chronic thromboembolic pulmonary hypertension
Authors: Onishi H , Taniguchi Y , Matsuoka Y , Yanaka K , Izawa Y , Mori S , Otake H , Satomi-Kobayashi S , Emoto N , Hirata K
Published: October 2019

Background

The existence of microvasculopathy in patients with chronic thromboembolic pulmonary hypertension (CTEPH) had been suggested. However, the impact of microvasculopathy for pathophysiology had been unknown. Recently dual-energy CT (DECT) can produce a sensitive iodine distribution map as blood perfusion in lung fields to quantify lung perfusion, also can suggest the existence of microvasculopathy according to poor subpleural perfusion which was published previously.

Methods

We retrospectively reviewed poor subpleural perfusion (defined as subpleural spaces either not or minimally perfused in all segments) and hemodynamics of 83 treatment-naïve CTEPH patients who underwent DECT from February 2014 to Jan 2019. Patients were divided according to poor subpleural perfusion: a microvasculopathy group (n=44) or a non-microvasculopathy group (n=39).

We assessed cardiopulmonary exercise test, right heart catheterization and DECT parameters as quantitative evaluation of pulmonary blood volume (PBV). PBV was calculated as the average of entire lung iodine density.

Results

PBV value in non-microvasculopathy group showed significant inverse correlation with pulmonary vascular resistance (PVR) (y = 14236 x-1.028 r=−0.530, p<0.01).

PBV, SvO2, and %DLCO/VA were significantly lower (22.0 vs. 26.4, p<0.01, 61.3 vs. 66.0, p<0.01, and 59.2 vs 75.9 p<0.01), and systolic pulmonary arterial pressure, PVR, VE/VCO2 slope, BNP were higher (69.3 vs 60.6 p=0.04, 834 vs 586 p<0.01, 45.5 vs. 37.8, p=0.02, and 440 vs 122 p=0.04) in microvasculopathy group, while the other parameters were similar between the two groups.

Multivariate analysis revealed that %DLCO/VA was the only predictor of microvasculopathy (OR,0.895 [95% CI, 0.835 - 0.960]; P<0.01).

Conclusion

Pulmonary blood flow of patients in non-micorvasculopathy group showed inverse correlation with PVR. DECT was effective to assess the microvasculopathy in CTEPH. In our experience, less than 60% of non-operable CTEPH patients have microvasculopathy.
P5024Pathogenic mechanism of DSG2-F531C mutation caused arrhythmogenic right ventricular cardiomyopathy
Authors: Wang D , Zhou X , Guo Y , Yang B
Published: October 2019

Objective

Mutations in the Desmoglein-2 (DSG2) are associated with arrhythmogenic right ventricular cardiomyopathy (ARVC). We previously identified a highly conserved F531C (c.1592T>G) variant of the cardiac desmosome gene DSG2 in the proband with a positive family history. The aim of this study is to investigate the mechanism(s) of DSG2-F531C variant in the pathogenesis of ARVC.

Methods

A large Han Chinese family with five generations was enrolled in this study, physical and clinical examinations were performed. Seven members were diagnosed with ARVC. Subsequently five desmosomal genes (PKP2, DSG2, DSP, DSC2 and JUP), TMEM43 and PLN were sequenced directly from genomic DNA. Seven patients diagnosed with ARVC were homozygous for DSG2-F531C, while five members of the family with normal phenotype were heterozygous for DSG2-F531C. To further explore the role of DSG2-F531C in ARVC pathogenesis, we generated a knock-in (KI) mouse model, which was carrying the mouse equivalent form (DSG2-F536C) of this variant.

Results

The homozygous KI mice (DSG2-F536C+/+) revealed a robust cardiomyopathy phenotype with left ventricular systolic dysfunction, histopathology showed accumulation of collagen, spotty calcification and fat droplets with extensive fibrosis in ventricular tissue in all DSG2-F536C+/+ mice. Further detections showed widening of the intercalated disc and regional loss of DSG2 in the hearts of these mice. The marked reduction in immunoreactive signal for sodium voltage-gated channel alpha subunit 5 (NaV1.5) was observed with no apparent changes in plakoglobin and connexin-43. In addition, dramatically elevated expression of transforming growth factor β1 (TGF-β1) was also found in the DSG2 mutant mice. Intriguingly, the heterozygous KI mice (DSG2-F536C+/−) expressed a similar level of TGF-β1 versus homozygous ones (DSG2-F536C+/+), but exhibited slight changes in morphology.

Conclusions

The DSG2-F536C KI mice produce a similar pathological phenotype of human ARVC, which supports DSG2-F531C as a causative mutation for ARVC. Additionally, the DSG2-F536C+/+ mutation induced cardiac fibrosis through the activation of TGF-β1 signaling will open new opportunities for further mechanistic and therapeutic studies in DSG2-related ARVC.

Acknowledgement/Funding

National Key R&D Program of China [2017YFC0909400); National Key Basic Research Program of China [973 program No. 2013CB531105]
P5027Prognosis and evaluation of the risk markers of arrhythmia in a large population of Brugada syndrome patients
Authors: Probst V , Anys S , Sacher F , Briand J , Guyomarch B , Tixier R , Berthome P , Babuty D , Thollet A , Mansourati J , Dupuis J M , Wiart F , Mabo P , Behar N , Gourraud J B
Published: October 2019

Introduction

Brugada syndrome (BrS) is an inherited arrhythmia syndrome with an increased risk of sudden cardiac death (SCD) despite a structurally normal heart. Many parameters have been suggested to be associated with the risk of ventricular arrhythmias, but only previous symptoms and spontaneous ECG pattern have been consistently associated with the risk of ventricular arrhythmia occurrence.

Objective

The aim of this study was to evaluate the association of these parameters with arrhythmic events in the largest cohort of BrS patients ever described.

Methods

Consecutive patients affected with BrS were recruited in a multicentric prospective registry in France (15 centers) between 1994 and 2016. Data were prospectively collected with an average follow-up of 6.5±4.7 years. ECGs were reviewed by 2 physicians blinded to clinical status.

Results

In this study, we enrolled a total of 1613 patients (mean age 45±15 years; 1119 males, 69%). At baseline, 462 patients (29%) were symptomatic (51 (3%) aborted SCD, 257 (16%) syncope). A spontaneous type 1 ECG pattern was present in 505 patients (31%). Implantable cardiac defibrillator was implanted in 477 patients (30%).

During the follow-up, 91 patients (6%) underwent arrhythmic events (16 SCD (10%), 48 appropriate ICD therapy (3%) and 27 ventricular arrhythmias (2%). Thirty-six patients (2%) died of non-arrhythmic causes. Mean age at the first event was 44±15 years.

In our cohort, event predictors were SCD (HR: 18.3; 95% CI: 11.2–29.8; p<0.0001), syncope (HR: 2.9; 95% CI: 1.8–4.9; p<0.0001), age >60 years (HR: 0.11; 95% CI: 0.032–0.377; p=0,0004), gender (HR: 2.96; 95% CI: 1.6–5.4; p=0.0005), spontaneous type 1 (HR: 2.14; 95% CI: 1.42–3.23; p=0.0003), type 1 ST elevation in peripheral ECG lead (HR: 3.6; 95% CI: 1.9–7.1; p=0,0001), fragmented QRS (HR: 3.37; 95% CI: 1.37–8.32; p=0,008), AvR sign (HR: 2.2; 95% CI: 1.4–3.8; p=0,0007), QRS >120ms in D2 lead (HR: 2.2; 95% CI: 1.4–3.6; p=0,001) and QRS >90ms in V6 (HR: 2.1; 95% CI: 1.3–3.3; p=0,001). All the others parameters including early repolarization pattern (ERP) and EPS were not predictor of events.

Conclusion

In the largest cohort of BrS patients ever described, we confirmed that symptoms, age, gender, spontaneous type 1, type 1 ST elevation in peripheral ECG lead, fragmented QRS, AvR sign, QRS >120ms in D2 and QRS >90ms in V6 are associated with arrhythmic events whereas ERP and EPS were not.
P5028Shanghai score system into practice
Authors: Carvalho P , Gravinese C , Varalda G P , Previti A , Mandrile G , Giachino D F , Pozzi R
Published: October 2019

Background

The 2016 J Wave Syndrome Consensus Report proposed the Shanghai Brugada Syndrome (BS) Score, a diagnostic score based on ECG features, genetic results, family and clinical history.

Purpose

The aim of our study was to reclassify our institution's BS cohort using the Shanghai BS Score.

Methods

We collected 170 patients with BS diagnosis (according to guidelines) who attended our outpatient clinic between 1996 and 2019. Patients were followed on an yearly basis. During follow up (FU) we looked for the appearance of a spontaneous Type 1 ECG (either with a 12 lead ECG or a 12 lead Holter monitoring) and arrhythmic events (defined as unexplained cardiac arrest or documented VF/polymorphic VT, nocturnal agonal respirations, syncope, atrial flutter/fibrillation). Genetic analysis, limited to SCN5A and SCN1B variants, was performed. We examined each item of the Shanghai BS Score at the first and the last visit at our hospital.

Results

At baseline all patients presented a type 1 ECG: 26 (15%) spontaneously, 2 (1%) during a febrile illness and 142 (84%) after ajmaline pharmacological challenge. 158 (93%) patients were asymptomatic while 12 (7%) presented symptoms: 1 unexplained cardiac arrest, 1 nocturnal agonal respirations, 9 syncopes, 1 atrial flutter/fibrillation under the age of 30 years. Genetic testing was performed in 73 (43%) patients; an SCN5A mutation was detected in 11 patients while a SCN1B was detected in 1 patient.

According to the score we divided the patients as follows: group A 2 to 3 points 107 (63%) patients; group B 3.5 points 13 (8%) patients; group C 4 to 5 points 39 (23%) patients; group D ≥5.5 points 11 (6%) patients.

During FU (medium 59 months) there were 3 (2.8%) arrhythmic events in group A (2 unexplained cardiac arrests and 1 syncope; 0 in group B; 1 (2.6%) in group C (syncope); 3 (27%) in group D (1 FV and 2 syncopes).

19 patients (11%) modified their Shanghai score during FU: 16 because of the appearance of a spontaneous type 1 ECG, 3 for their clinical history.

Conclusions

Although the Shanghai Score has been proposed as a diagnostic tool, data from literature show that patients with a higher score are at a progressively higher risk for VT/VF. Unexpectedly, we observed 2 unexplained cardiac arrests in the group of patients with a score 2 to 3. This may suggest the need to the use other risk criteria such as fractionated potentials or other ECG markers. Additionaly, we have shown that this Score is prone to changes over time, stressing the importance of a regular FU with continuous risk assessment.
P5235A technological approach to improving efficiency of primary to secondary care referrals
Authors: Graby J , MacConnell T
Published: October 2019

Introduction

Recognised in the 2019 NHS Long-term plan was the need to streamline services, with less face-to-face outpatient (OP) care by utilising digital technology and creating “virtual clinics” (VC). A team of Cardiologists and General Practitioners (GP) collaborated to create a VC via a web-based video link, enabling discussion of patients being considered by primary care for referral to the Cardiology clinic with members of the GP team present to: identify appropriate patients for OP review, enable early selection of investigations, identify patients not requiring further assessment. We aimed to assess the safety and efficacy of this approach.

Methods

VC's were established between a Consultant Cardiologist and two primary care practices. All referrals required an ECG. Each patient was presented by the referring GP, with all others present in the room to enable an educational experience. Consultant Cardiologist issued correspondence and co-ordinated any required tests and follow-up. A 13 month period of this practice was reviewed with 135 patient events screened via a cross-matched record of patients. Data was recorded for: indication for discussion; outcome; likelihood patient would have had test or referral made without this service (as assessed by Cardiology), and whether patients discussed had unplanned admissions or assessments.

Results

8/135 were excluded (duplication; admitted prior to VC; not discussed; re-discussed for learning). Efficacy: The overall number of patients a GP “would” have referred were 113 (89%), and the number “would” have had tests booked 98 (77%), across the two practises. This left an overall OPA post VC of 11% vs potential 89% “would” have been referred (100 potential appointments avoided), and an overall test rate post SAC 48% vs 77% “would” have had tests (37 potential tests avoided).

Safety

Unplanned Cardiology input post-VC included 1 subsequent chest pain clinic (different issue to VC), and 1 admission with syncope (discussed in SAC), with nil found.

Table 1 No Further Input Blood Test Cardiac Test OPA Primary Care 1 21 (40%) 3 (6%) 25 (47%) 4 (7%) Primary Care 2 32 (43%) 0 (0%) 32 (43%) 10 (14%) Overall 53 (42%) 3 (2%) 57 (45%) 14 (11%) Distribution of plan made in VC including: no further input required; blood test in Primary Care; Cardiac test in hospital only; outpatient Cardiology clinic (OPA).

Conclusion

The reduction in OPA and tests demonstrates improvement resource untilsation, and safety data was encouraging. This service demonstrates a novel approach to technology-enabled streamlining of primary to secondary care services in a safe and efficient manner.
P5239Cost-effectiveness of direct oral anticoagulants for cancer-associated venous thromboembolism
Authors: King J , Bhat S , Heath L J , Derington C G , Yu Z , Clark N P , Witt D M , Reynolds K , Lang D T , Xu S , Bellows B K
Published: October 2019

Background

Direct oral anticoagulants (DOACs) are at least as effective as low-molecular weight heparins (LMWH) at preventing recurrence after cancer-associated venous thromboembolism (CA-VTE). DOACs are also oral and far less costly, but they may confer a higher bleeding risk than LMWH.

Purpose

To estimate the cost-effectiveness of DOACs and LMWHs for CA-VTE.

Methods

We developed a health state transition model to estimate recurrent VTE, bleeding events, quality-adjusted life years (QALY), and direct healthcare costs (2018 United States dollars) associated with DOACs vs. LMWH use. The model had four states: (1) long-term anticoagulation (first 3 months after VTE), (2) extended anticoagulation (more than 3 months after VTE), (3) off anticoagulants, and (4) death. We used a United States healthcare sector perspective, 3-month cycle length, and 1-year time horizon. Event probabilities were derived from the Hokusai Cancer VTE trial and other literature. Event and medication costs were obtained from national sources. We used a threshold of less than $50,000 per QALY gained to define cost-effectiveness.

Results

Compared to LMWH, DOACs were less costly (mean costs: $8,477 vs. $33,917 per year) and similarly effective (mean QALY: 0.616 vs. 0.622). The incremental cost-effectiveness ratio was $4,479,374 per QALY gained with LMWH, indicating that DOACs are cost-effective (Table 1). In threshold analyses, LMWH therapy only became cost-effective when DOAC recurrent VTE risk increased to at least 72% (relative risk vs. LMWH, 6.19) or DOAC clinically relevant bleeding increased to at least 39% (relative risk vs. LMWH, 10.09).

Scenarios Recurrent VTE, % Major bleed, % Mean difference DOAC − LMW ICER DOAC LMWH Relative Risk DOAC LMWH Relative Risk Cost QALY Base case 8.1 11.6 0.71 6.8 4.0 1.75 −$25,440 (−26,496, −24,274) −0.006 (−0.019, 0.008) $4,479,374 DOAC outcome rate threshold at which LMWH becomes cost-effective*   Recurrent VTE 71.5 11.7 6.19 – – – −$6,064 (−7,534, −4,627) −0.121 (−0.136, −0.108) $49,886   Major Bleed – – – 38.9 4.0 10.09 −$2,192 (−3,400, −704) −0.044 (−0.056, −0.030) $49,878 DOAC = direct oral anticoagulant, ICER = incremental cost-effectiveness ratio, LMWH = low-molecular-weight heparin, VTE = venous thromboembolism. Values are mean (95% Uncertainty Interval). Uncertainty was derived from 1,000 stochastic model iterations. *Represents the minimum increased risk with DOAC that would result in LMWH achieving an ICER <$50K per QALY gained.

Conclusion

In this simulation study, DOACs were a cost-effective oral alternative to LMWH for the treatment of CA-VTE. For LMWH to be cost-effective, DOAC event rates needed to be far higher than what is likely to be observed in clinical practice.

Acknowledgement/Funding

Agency for Health Research and Quality R18HS026156
P5247In-hospital healthcare utilization, outcomes and costs in pre-hospital adjudicated low-risk chest pain patients
Authors: Van Dongen D N , Ottervanger J P , Tolsma R , Fokkert M , Badings E , Sluis A , Van 'T Hof A , Slingerland R
Published: October 2019

Background

There is increasing evidence that in patients presenting with acute chest pain, pre-hospital triage can accurately identify low-risk patients. It is, however, yet unclear which diagnostics are performed in pre-hospital adjudicated low-risk patients and what the contribution is of those diagnostic results in the healthcare process.

Objectives

The aim of this study is to quantify health care utilization, costs and outcomes in pre-hospital adjudicated low-risk chest pain patients, and to extrapolate to costs on a national level.

Methods

This is a prospective cohort study including 700 patients with suspected NSTE-ACS in which pre-hospital risk stratification using the HEART score was performed by paramedics. Low risk was defined as a pre-hospital HEART score ≤3. Data on (results of) hospital diagnostics, costs and discharge diagnosis were collected.

Results

A total of 172 (25%) patients were considered as low risk. Of these low-risk patients, mean age was 54 years, 52% were male, 84% of patients were discharged within 12 hours. Repeated electrocardiography and routine laboratory measurements, including cardiac markers were performed in all patients. Chest X-ray was performed in 61%, echocardiography in 11% of patients. After additional diagnostics, 2 patients (%) were diagnosed as non-STEMI, 2 patients (%) as unstable angina. Other diagnoses were atrial fibrillation (n=1) and acute pancreatitis/cholecystitis (n=2), all other patients had non-specific/non-acute discharge diagnoses. Mean in-hospital costs per patient were €1.580,-. The estimated yearly acute healthcare costs in low-risk chest pain patients in the Netherlands are € 30.438.700,-

Conclusion

In low-risk chest pain patients according to pre-hospital risk assessment, acute healthcare utilization and costs are high, with limited added value. Possibly, if a complete risk assessment can be performed by ambulance paramedics, acute hospitalization of the majority of low-risk patients is not necessary which can lead to substantial cost reduction.
P5249Comprehensive invasive and non-invasive assessment of coronary artery lesions with and without hemodynamic significance
Authors: Engel L C , Landmesser U , Abdelwahed Y , Gigengack K , Manes C , Wurster T.-H , Skurk C , Leistner D.-M , Lauten A , Schuster A , Noutsias M , Hamm B , Botnar R M , Makowski M , Bigalke B
Published: October 2019

Background

There is limited knowledge about specific morphological parameters beyond the degree of stenosis to further characterize hemodynamically relevant coronary lesions.

Objective

The goal of this study was to identify certain morphological or molecular characteristics that distinguish hemodynamically significant from non-significant coronary lesions using various invasive and non-invasive measures.

Methods

This clinical study included patients with symptoms suggestive of CAD who underwent native T1-weighted CMR and gadofosveset-enhanced CMR as well as invasive coronary angiography between 2015 and 2016. OCT of the culprit vessel to determine the plaque type was performed in a subset of patients. Functional relevance of all lesions was examined using quantitative flow reserve (QFR-Angio). Hemodynamically significant lesions were defined as lesions with a QFR <0.8. Signal intensity (contrast-to-noise ratios; CNRs) on native T1-weighted CMR and gadofosveset-enhanced CMR was defined as a measure for intraplaque hemorrhage and endothelial permeability respectively.

Results

Overall 13 patients (n=28 coronary segments) were included, whose invasive coronary angiograms projections were eligible for QFR analysis. Segments containing lesions with a QFR <0.8 (n=9) were associated with significantly higher signal enhancement on Gadofosveset-enhanced CMR as compared to segments containing a hemodynamically non-relevant lesions (lesion-QFR>0.8; n=19) (7.0±4.9 vs. 3.0±2.6; p=0.02). No differences in signal enhancement were seen on native T1-weighted CMR (2.1±4.3 vs. 3.3±4.1; p=0.24). 66,7% (4 out of 6) of all vulnerable plaque and 33.3% (2 out of 6) of all non-vulnerable plaque (fibroatheroma) as assessed by OCT were hemodynamically significant lesions.

Conclusion

The findings of this small feasibility study suggest that hemodynamically significant lesions are more advanced and associated with a higher grade of endothelial permeability while the presence of intraplaque hemorrhage may not be associated with hemodynamically relevant coronary lesions.
P5254Prognostic value and clinical predictors of Intramyocardial Hemorrhage measured by CMR T2* weighted sequences
Authors: Igual Munoz B , Ferre M F V , Sanchez E S L C , Diez J L , Plaza Lopez D , Paya R P S , Berenguer A B J , Sepulveda Sanchez P , Miro Palau V , Montero A M A , Morell S M C , Martinez Dolz L
Published: October 2019

In the setting of STEMI, microvascular injury consists of microvascular obstruction (MVO) and intramyocardial hemorrhage (IMH). We aimed to investigate prognostic value and clinical predictors of MR T2* w analysis of IMH in this setting.

Methods

A single center observational cohort study was performed in patients with reperfused STEMI with CMR examination after percutaneous revascularization. Infarct related CMR characteristics were analyzed in whole LV short-axis late gadolinium enhancement sequences (LGE) for infarct size and MVO and whole volume T2*w sequences for IMH. Extent of MVO and IMH were derived as percentage of LV mass. Kaplan-Meier was used to analyze the incidence of major adverse cardiovascular events, defined as a composite of cardiac death, myocardial re-infarction, and new congestive heart failure.

Results

94 reperfused STEMI patients were included in the study. T2*w IMH was present in 26 (28%) patients and the median size of IMH was 1.1% (IQR: 0.5 to 2.9%). MVO was identified in 49 (52%) patients and the median size of MVO was 3% mass (IQR: 1.5 to 5.4%). T2*w IMH extension was independently associated with anterior myocardial infarction (p=0.022) and thrombectomy (p=0.049). IMH was correlated with MVO (R=0.62, p<0.001), necrosis (R=0.58, p<0.001) and LVEF (R=-0.21, p=0.04). Patients with IMH presented higher incidence of MACE, independently of LVEF (p=0.022).

Typical CMR sequences

Conclusions

Whole LV T2*w proves useful to asses IMH. IMH extension was associated with anterior infarction and thrombectomy. T2*w IMH was associated with higher incidence of MACE regardless preserved or reduced LVEF
P5264There is no significant effect of ischemic time and elapse time since cardiac allograft transplant on myocardial T1 relaxation time
Authors: Vietheer J , Unbehaun C , Classen K , Richter M , Rieth A , Rademann M , Keller T , Hamm C W , Rolf A
Published: October 2019

Background

Graft failure caused by allograft rejection and vasculopathy is the most common cause of mortality after heart transplantation. To detect an early allograft rejection, endomyocardial biopsy is still needed. Tissue characterization by T1-mapping and Late gadolinium enhancement is well established in acute and chronic myocardial tissue alterations. Therefore several studies investigated T1-mapping as a potential noninvasive parameter to monitor cardiac allograft vasculopathy and allograft rejection. However it is unclear if T1 is also influenced by pretransplant ischemic time and elapsed time since transplantation.

Purpose

It was the aim of our study to examine the influence of ischemic and elapsed time since transplantation to the cardiac allograft tissue characteristics measured by CMR T1 relaxation times.

Methods

Allograft transplant patients underwent stress CMR on a yearly routine. T1-maps were acquired using a modified look locker sequence (MOLLI 3(2)3(2)5) in the midventricular septum. Uni- and multi linear regression analysis was used to predict T1 by ischemic time, time since transplantation, troponin and NT-Pro-BNP.

Results

49 cardiac allograft transplanted patients underwent stress CMR (mean age 58.6±11.7 years, left ventricular ejection fraction 62.1±6.8%; indexed enddiastolic volume 68.4±14.7 ml/m2; native T1 1120±51 ms, extracellular volume 0.27±0.04). A significant correlation was found between T1 and NT-Pro-BNP (1519±3639 pg/ml, p=0.003) and a trend for troponin (17.0±12.8 ng/dl, p=0.051). We saw no correlation between T1 and the ischemic time (198.4±44.9 minutes, p=0.1172) and elapse time since transplantation (47±7 month, p=0.9868). In the multivariate regression analysis none of the four parameters were independently associated with the T1 time (p=0.1017).

Table 1 Characteristics Mean ± SD p Ischemic time (minutes) 198.4±44.9 0.1172 Time since transplant (month) 47±7 0.9868 NT-Pro-BNP (pg/ml) 1519±3639 0.003 Troponine (ng/dl) 17.0±12.8 0.051

Conclusion

There was no significant effect of pretransplant ischemic time and elapse time since transplantation on native T1 times, whereas native T1 was significantly correlated with troponine and NT-Pro-BNP-Levels. T1 is excellently suited to detect acute changes in allograft transplant patients without being influenced by aging of the transplanted heart and the heart's pretransplant condition.
P52714D-flow cardiac magnetic resonance analysis of left ventricular blood flow dynamics in mid-ventricular obstructive hypertrophic cardiomyopathy
Authors: Miyajima K , Shirai Y , Kin F , Watanabe T , Tatsuguchi M , Kawaguchi Y , Wakabayashi Y
Published: October 2019

Background

Mid-ventricular obstructive hypertrophic cardiomyopathy (MVO-HCM) has different blood flow dynamics from other phenotypes, but there are few detailed data on blood flow dynamics in the left ventricle.

Methods

4D-Flow MRI were performed at 1.5 T or 3 T with 9 MVO-HCM patients and 22 control patients (LVEF>50%, no wall motion abnormality). Myocardial infarction, severe valvular disease, HCM cases other than MVO were excluded. We calculated the cardiac function parameters and observed blood flow dynamics in the left ventricle using 4D-Flow MRI.

Results

LV mass was significantly higher in MVO-HCM group than in Control group (Control group; 73.3g vs MVO-HCM group; 109.5g, P=0.019). LVEF was higher in MVO-HCM group (Control group; 61.6% vs MVO-HCM group; 70.6%, P=0.026), but Stroke volume did not differ between the two groups (Control group; 68.8ml vs MVO-HCM group; 64.4ml, P=0.43).One or two vortices were observed in the left ventricle after opening the mitral valve. Two vortices were observed in 16 cases (72.7%) in the control group and 9 cases (100%) in the MVO-HCM group. Two vortices were formed on the anterior side and the posterior side. Blood flow pattern in which the vortex on the posterior side was formed to be the same size or larger than the vortex on the anterior side was observed only in the MVO-HCM group (Control group; 0% vs MVO-HCM group; 66.7%, P<0.001).

Streamline of MVO-HCM & Control

Conclusion

Characteristic blood flow patterns in the left ventricle of the MVO-HCM were revealed by using 4D-MRI. We thought that blood flow collides with the left ventricle wall due to the marked hypertrophy in the mid-ventricle, and normal vortex ring can not be formed in the MVO-HCM cases.
P5273Trabecular complexity as a subclinical structural alteration in Fabry cardiomyopathy: a cardiac magnetic resonance study
Authors: Lazzeroni D , Camporeale A , Moroni F , Garibaldi S , Pica S , Chow K , Camici P , Lombardi M
Published: October 2019

Background

Heart involvement represents the main cause of death in Fabry Disease (FD), thus its early detection is important to define the optimal therapeutic strategy. Recently, a disproportionate increase in myocardial trabeculation has been described in FD by cardiac magnetic resonance (CMR), even in early (prehypertrophic) stage of the disease. In addition, CMR with T1 mapping can identity the presence of myocardial sphingolipid storage (causing lowering of native T1 values) in more than 50% of FD patients with no LVH. However, it is not clear whether a relationship exists between trabecular complexity and sphingolipid storage in FD.

Aim

To explore the association between myocardial trabecular complexity, quantified by endocardial border fractal analysis, and sphingolipid storage, described by CMR T1 mapping, in different stages of Fabry cardiomyopathy.

Methods

Study population included 60 subjects: 15 FD patients with no detectable signs of cardiac involvement (no LVH, normal T1; 2 M, age 30.6±14; Group 1); 15 FD patients with early sphingolipid storage (no LVH, low T1; 9 M, age 33±9.6; Group 2); 15 FD patients with LVH (11 M, age 53.5±9.6; Group 3); 15 healthy controls (9 M, age 34±10). Patients and controls underwent CMR with T1 mapping; disease severity was quantified using Mainz Severity Score Index (MSSI). Myocardial trabecular fractal dimension was evaluated, blinded to patients'characteristics, on short axis cine images using the Image J dedicated plug-in FracLac, deriving the following parameters: total, basal, mid-ventricular and apical fractal dimensions.

Results

Total fractal dimension was higher in all Fabry groups compared to controls. Indeed, a gradient of total fractal dimension was observed, with this parameter gradually increasing from healthy controls to Groups 3 (1.27±0.02 in controls vs 1.29±0.02 in Group 1 vs 1.30±0.02 in Group 2 vs 1.34±0.02 in Group 3; p<0.001) (Figure 1A). Interestingly, both total and basal fractal dimensions were significantly higher in Group 1 compared to controls (1.27±0.02 vs 1.29±0.02, p=0.044 and 1.26±0.04 vs 1.30±0.03; p=0.007, respectively). Moreover, considering the total population, fractal dimension showed significant correlations with: i) T1 values (r=−0.567; p<0.001 - Figure 1B); ii) LV mass (r=0.674, p<0.001); iii) trabecular mass expressed as percentage of global LV mass (r=0.611; p<0.001); iv) MSSI (r=0.535; p<0.001).

Conclusion

Cardiac involvement in FD is characterized by a progressive increase in fractal dimension of endocardial trabeculae (Figure 1C). Both total and basal myocardial trabeculation are increased in Fabry patients even before the presence of detectable sphingolipid storage, thus representing a very early sign of cardiac involvement.
P5274Characterization of cardiac involvement in patients with MELAS syndrome in comparison to HCM patients by conventional LGE imaging and novel T1-mapping
Authors: Bietenbeck M , Florian A R , Meier C , Holtstiege V , Chatzantonis G , Yilmaz A
Published: October 2019

Background

MELAS syndrome (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) is a rare clinical subtype of mitochondrial myopathy. Cardiovascular magnetic resonance (CMR) images of MELAS-patients at an advanced state of the disease often show characteristic patterns: septal pronounced left ventricular (LV) hypertrophy and distinct focal myocardial scars in late-gadolinium-enhancement (LGE) images. This specific pattern is different from those seen in patients with hypertrophic cardiomyopathy (HCM) due to sarcomere protein mutations. Besides LGE imaging another method for the assessment of myocardial integrity, T1-mapping, has been established recently. This is the first study comparing native and enhanced T1-mapping (T1-na/en) as well as extracellular volume (ECV) values in HCM and MELAS.

Methods

12 patients with confirmed MELAS syndrome at different states of the disease, 13 HCM patients and 15 controls were included. All CMR studies were performed on a 1.5T MR scanner (Ingenia, Philips) using bSSFP cine sequences for the assessment of LV-function and MOLLI sequences for T1-na/en mapping. 15min after IV injection of 0.1mmol/kg BW Gadobutrol for LGE imaging, T1-en maps were acquired. For comparison of groups T1-na/en and ECV values in a basal short axis slice were used.

Results

Median and interquartile ranges of LV function, T1 and ECV are shown in the table. There was no difference in LV ejection fraction (LVEF) between the groups, but end-diastolic LV-mass was increased in HCM- and MELAS-patients vs. controls (p<0.001, p=0.028). In MELAS-patients, myocardial fibrosis was detected in focal spots clearly defined in both septum and free lateral wall. In HCM patients there was a rather diffuse LGE pattern in the hypertrophic septum and the RV insertion points. Here T1-na/en and ECV significantly differed from those measured in healthy controls (p<0.001, p<0.001, p=0.002). In the MELAS group T1-na values were significantly higher compared to controls (p=0.004) and significantly lower compared to HCM patients (p=0.003).

LV-function and mapping parameters of compared groups LV-EF, % LV-EDV, ml/m2 LV-mass, g/m2 T1-na, ms T1-en, ms ECV, % MELAS 57 (44–63) 86 (81–122) 80 (50–131) 969 (940–1033) 409 (381–465) 27 (24–35) HCM 60 (57–65) 50 (73–94) 94 (72–102) 1041 (1021–1074) 362 (346–430) 31 (28–36) Controls 61 (58–65) 72 (67–89) 53 (42–60) 937 (894–951) 464 (446–513) 26 (24–27)

Conclusion

Compared to healthy controls and HCM-patients, cardiac involvement in MELAS-patients is not only reliably visualized by conventional LGE imaging but also detected without the use of contrast agent by native T1-mapping. MELAS vs. HCM-patients show a different pattern of LGE and higher native T1 values, respectively.