bluuebunny/crossref_metadata_2025 huggingface dataset:
4313Evolocumab rapidly reverses impaired coronary endothelial function in six weeks in people living with HIV and in patients with dyslipidemia
Authors: Leucker T , Gerstenblith G , Schar M , Brown T , Jones S , Weiss R , Hays A
Published: October 2019

Background/Introduction

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is well recognized for its importance in cholesterol metabolism. Elevated levels are associated with increased cardiovascular risk and inhibition with PCSK9 antibodies lowers cardiovascular events in patients with known coronary disease. PCSK9 levels are also elevated in people living with HIV (PLWH), and we previously reported that increased PCSK9 in PLWH is associated with impaired coronary endothelial function (CEF), a major driver for the development, progression, and clinical manifestations of coronary artery disease.

Purpose

Here we investigate the hypothesis that PCSK9 inhibition improves impaired CEF in PLWH and in patients with dyslipidemia (DL).

Methods

Cine 3T MRI was used to noninvasively measure CEF, assessed as the change in coronary cross-sectional area (CSA) from rest to isometric handgrip exercise (IHE), a known endothelial-dependent vasodilator. Eight HIV+ subjects on stable highly active antiretroviral therapy and with undetectable HIV RNA (mean age 53±9 yrs, LDLC 98±18 mg/dL, 38% on statins) and ten patients with dyslipidemia (DL) without HIV receiving evolocumab for clinical reasons (mean age 56±10 yrs, LDLC 130±28 mg/dL, 50% on statins) underwent MRI studies before and six weeks following the initiation of evolocumab 420 mg. MRI readers were blinded to group and timepoint. MRI data are presented as mean±SD for % change rest vs IHE.

Results

Prior to evolucumab, resting CSA in the two groups did not differ and IHE did not induce normal coronary vasodilation in either group; mean stress-induced CSA changes were −2.1±6.4% in HIV (p=0.27) and −0.6±4.1% in DL (p=0.46). Notably, CEF significantly improved following six weeks of evolocumab with IHE-induced CSA changes of 7.6±5.7% (p=0.006) and 5.0±3.6% (p=0.002) in the HIV and DL groups, respectively. The %-LDLC reduction with evolocumab was profound and comparable in the HIV and DL groups, 73±5% and 60±6% (p=0.19 HIV vs. DL). There was no significant correlation between the extents of LDLC reduction and of CEF improvement in either of these modest sized groups.

Conclusion

PCSK9 inhibition with evolocumab significantly improves abnormal coronary endothelial function after only six weeks in HIV+ people with normal LDLC and in HIV- people with DL. To our knowledge, these data represent the earliest (6 weeks) evidence for improvement in human coronary artery health by PCSK9 inhibition.

Acknowledgement/Funding

Amgen provided the PCSK9 monoclonal antibody (evolocumab) for this study.
4329Mega-studies in heart failure, effect dilution in examination of new therapies
Authors: Cotter O , Davison B A , Koch G , Senger S , Metra M , Voors A A , Mebazza A , Nielsen O W , Chioncel O , Pang P , Greenberg B H , Maggioni A , Sato N , Teerlink J R , Cotter G
Published: October 2019

Aims

All phase 3 studies in patients with acute heart failure (AHF) and HF with preserved ejection fraction (HFpEF) have failed in the last decades. We explore the likelihood that the negative results are due to chance and/or to study size and dilution of statistical power.

Methods and results

First, using simulations, we examined the probability that a positive finding in phase 2 would result in studying truly effective drugs in phase 3. We simulated phase 2 studies under six scenarios where the range of true relative risk (RR) for an outcome of interest varied from 0.5 (major benefit) to 1.15 (some harm). The proportion of simulated studies where the RR <0.8 (we assumed that a 20% or greater risk reduction reflects an effective drug) ranged from 6% to 42% across the six scenarios studied. To further simulate “real life” clinical research, we simulated a continuous surrogate outcome that was linearly related to the true RR in each simulation of each scenario. Regardless of criteria considered for a positive phase 2 trial, results suggest that even in our worst-case scenario, where overall only 6% of drugs taken into phase 2 are effective, roughly 20% of phase 3 studies, if appropriately powered, should have yielded positive results. Given this, we then explored study size in AHF research, as a potential explanation for the high failure rate in these studies. Comparison of published phase 2 and 3 clinical trials with registries in AHF suggest that populations in both large and small trials differ from “real life”. Meta-regression models suggest that both control event rates, and in the serelaxin program as an example, treatment effects, decline with increasing study size greatly reducing power (figure). This effect dilution might be explained by an increasing proportion of patients enrolled in studies who cannot benefit from the study drug.

Figure 1. Power at two-sided 0.05 significance level to detect an effect size of hazard ratio of 0.65 (left) or 0.8 (right) with a placebo event rate of 10% (top) and 20% (bottom) at N=100 at various treatment effect dilutions with increasing sample size.

Conclusion

These data suggest that it is unlikely that the very high rate of negative AHF phase III trials can be explained by chance alone. Potentially, our tendency to increase sample size does not necessarily increase statistical power, due to more heterogenous populations leading to reduced event rates and treatment effects.
P3095Left ventricular thrombus formation after ST-elevation myocardial infarction: a prospective observational CMR study
Authors: Holzknecht M , Reinstadler S J , Reindl M , Tiller C , Mayr A , Klug G , Metzler B
Published: October 2019

Background

Left ventricular (LV) thrombus formation is a severe complication after acute ST-segment elevation myocardial infarction (STEMI). The incidence and determinants of LV thrombus formation are still a matter of controversy.

Purpose

We aimed to assess the incidence as detected by cardiac magnetic resonance (CMR) imaging as well as the determinants of LV thrombus formation in contemporary reperfused STEMI patients.

Methods

This prospective observational study included 530 consecutive STEMI patients treated with primary percutaneous coronary intervention (PCI). Comprehensive CMR was performed at a median of 3 days (interquartile range 2–4 days) after symptom onset for the evaluation of LV thrombus formation as well as LV function and infarct severity.

Results

LV thrombi were detected in 17 patients (3.2% of the overall cohort). The incidence of LV thrombi in anterior STEMI patients (n=247) was 6.9%. In all patients presenting with LV thrombus left anterior descending artery (LAD) was identified as culprit lesion. The occurrence of thrombi was significantly associated with reduced LV ejection fraction (LVEF) (p<0.001), larger LV end-diastolic volume (p<0.001) and LV end-systolic volume (p<0.001), larger areas of microvascular obstruction (MVO) (p=0.003) and larger infarct size (IS) (p<0.001). Furthermore, increased levels of peak high sensitivity cardiac Troponin T (p<0.001) and hyperlipidaemia (p=0.038) were significantly related to LV thrombi. In multivariable analysis including IS, LVEF and MVO, only LVEF (odds ratio: 0.91 (95% confidence interval: 0.87–0.96); p=0.001) emerged as independent predictor of LV thrombus formation.

Conclusion

The risk of LV thrombus formation remains considerable in contemporary treated STEMI patients, especially in those with LAD as culprit lesion. Among CMR parameters of LV dysfunction and infarct severity, only baseline LVEF, but not IS or MVO, independently predicted LV thrombus formation after STEMI.
P3098Association with coronary high-intensity plaque on T1-weighted magnetic resonance imaging and circulating levels of malondialdehyde-modified low-density lipoprotein
Authors: Hiraya D , Sato A , Hoshi T , Ichinohe T , Sakai S , Watabe H , Ieda M
Published: October 2019

Objectives

This study aimed to evaluate the association with coronary high-intensity plaque (HIP) on non-contrast T1-weighted magnetic resonance imaging (T1WI) and circulating levels of malondialdehyde-modified low-density lipoprotein (MDA-LDL).

Methods

A total of 139 patients with coronary artery stenosis (>70%) were imaged with non-contrast T1WI by using a 1.5-T magnetic resonance system (HIP: n=60, non-HIP: n=79). HIP was defined as a signal intensity of coronary plaque to cardiac muscle ratio (PMR) of ≥1.4. At admission, circulating levels of MDA-LDL and other lipid-related markers (triglyceride, HDL, LDL, Lp(a), RLP-C, and EPA/AA) were measured.

Results

Circulating levels of MDA-LDL (p=0.001) and LDL (p=0.041) were significantly higher in patients with HIP than those without, whereas the other lipid-related markers were not significantly different between both groups. In multivariable logistic regression analysis, MDA-LDL levels were independently associated with the presence of HIP (OR 1.03; 95% CI, 1.00–1.06, p=0.015) after adjusting for cofounding factors (age, sex, triglyceride, LDL, Lp(a), RLP-C, and EPA/AA). The optimal MDA-LDL threshold for predicting coronary HIP was 90.4 U/L, identified by the receiver operating characteristic curve.

Conclusion

MDA-LDL levels might be associated with the presence of HIP in patients with coronary artery disease.
P3104Complementary impact of glycated haemoglobin and B-natriuretic peptide on cardiopulmonary exercise capacity in patients with ischemic heart disease
Authors: Uribe-Heredia G , Arroyo-Espliguero R , Viana-Llamas M C , Piccone-Saponara L G , Alvaro-Fernandez H , Garcia-Magallon B , Castillo-Sandoval A , Toran-Martinez C
Published: October 2019

Background

Glycemic control, even in non-diabetes mellitus (DM) patients, has been associated with ventilation pump inefficiency leading to an impaired aerobic capacity. Brain natriuretic peptide (BNP) levels have also been correlated with exercise capacity, particularly in patients with heart failure.

Purpose

Assess the complementary impact of glycated haemoglobin (HbA1c) and BNP levels on cardiopulmonary exercise capacity in patients with ischemic heart disease (IHD).

Methods

Retrospecive cohort of 91 consecutive patients (57±10 years, 90% men; 29% type 2 DM) who underwent a cardiopulmonary exercise testing (CPX) at the beginning of an standard phase-II cardiac rehabilitation program, 2–3 months after an acute coronary syndrome.

Results

HbA1c and BNP levels correlated with peak oxygen uptake (VO2), anaerobic threshold (AT) and pulse O2 trajectory (Table). HbA1c correlated with ventilation CPX parameters (Table) and independently predicted minute ventilation (VE) and tidal volume (VT), regardless of age, waist circumference and β-blocker therapy. BNP levels correlated with echocardiographic (LVEF, left atrium size and pulmonary artery systolic pressure) and ventilation-perfusion (V/Q) mismatch parameters (Table), and independently predicted VE/VCO2-slope (P=0.037) regardless of age, echocardiographic parameters and β-blocker therapy. Patients were divided into three groups according to HbA1c levels above or below the DM diagnosis cut-off point (6.5%) and median value of BNP levels (44.6 pg/mL). VO2 and AT significantly decreased with elevated HbA1c and/or BNP levels (Figure).

CPX parameters HbA1c (%) BNP (pg/mL) r P value r P value Peak VO2 (mL/min/kg) −0.421 <0.001 −0.295 0.005 VO2 at AT (mL/min/kg) −0.352 0.001 −0.271 0.009 O2 pulse trajectory (mL/beat) −0.345 0.001 −0.235 0.025 Minute ventilation (VE) (L/min)* −0.377 <0.001 – NS Tidal volume (VT) (L)* −0.348 0.001 – NS VE/VCO2-slope – NS 0.375 <0.001 PETCO2 at AT (mmHg) – NS −0.315 0.002 HR/VO2-slope – NS 0.307 0.003 *At peak exercise. NS: Non-significant.

Conclusions

HbA1c and BNP levels were associated with a reduced cardiopulmonary capacity in IHD patients, mediated by a ventilation impairment and a ventilation-perfusion mismatching, respectively. HbA1c and BNP are independent and additive predictors of cardiopulmonary capacity.
P3105Cardiopulmonary exercise testing normal values for young athletes and non-athletes
Authors: Sydo N , Csulak E , Major D , Erdi J , Sydo T , Gyore I , Petrov I , Czimbalmos C S , Vago H , Lakatos B , Kovacs A , Allison T G , Merkely B
Published: October 2019

Introduction

Cardiopulmonary exercise testing (CPET) is an important diagnostic method to evaluate athletes and non-athletes, however we do not have widely accepted normal values for correct evaluation and interpretation in the young.

Goals

Our aim was to compare CPET parameters of young athletes and non-athletes and determine reference values.

Methods

Exercise tests were performed in young non-athletes, aged <18 years between 2011 to 2016 at Mayo Clinic. Athletes underwent detailed sports cardiology screening including CPET at Semmelweis University Heart and Vascular Center between 2016 and 2018. Individuals with cardiovascular disease were excluded. We created 2 subgroups in both sexes: 12–14 years (Group 1), 15–17 years (Group 2). Statistical analysis was performed using SAS with analysis of variance under the general linear model adjusting for age, body mass index and test effort based on peak respiratory exchange ratio (RER).

Results

A total of 212 athletes (92% male, 15.5±0.6ys) and 207 non-athletes (68% male, 15.0±0.7ys) were included in the analysis. In Group 1 boys, athletes have higher peak HR (200.0±9.2 vs 188.5±16.8 bpm, p<0.0001), HR reserve (117.1±14.5 vs 108.9±19.8 bpm p<0.05), VO2 max (53.7±6.6 vs 44.7±9.1 mL/kg/min p<0.0001), ventilation (VE) (120.3±25.0 vs 70.7±21.6 L/min p<0.0001) and RER (1.12±0.0 vs 1.07±0.08, p <.001) compared to controls. In Group 2 boys, there was no difference in peak HR and HR reserve, but athletes have higher VO2 max (57.2±4.7 vs 45.3±9.3 mL/kg/min, p<0.0001) and VE (150.7±23.7 vs 104.1±25.9 L/min, p<0.0001), similarly as Group 2 girls: VO2 max (46.3±3.6 vs 34.9±8.5 mL/kg/min p<0.0001), VE (118.7±12.5 vs 68.4±20.6 L/min, p<0.0001). In male athletes, peak HR (200.6±9.2 vs 196.5±7.4 bpm p<0.05) and HR recovery (34.2±9.8 vs 29.8±11.1 bpm p<0.05) decreases with age, while VO2 max (53.7±6.6 vs 57.2±4.7 mL/kg/min, p<0.001) and VE (120.3±24.9 vs 150.7±23.7 L/min, p<0.0001) increases. Lower cut-off values were determined in each group (Figure).

Lower-cut off values

Conclusion

We created a unique Mayo-Semmelweis database of young athletes and non-athletes. As a result of intensive training, athletes show higher levels of CPET variables vs non-athletes. Our study provides CPET reference values in the pediatric age group, applying them could contribute to correct evaluation and interpretation of CPET, increasing its diagnostic potential.
P3123Enoxaparin versus unfractionated heparin in ST-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention
Authors: Graca Santos L , Ribeiro Carvalho R , Montenegro F , Ruivo C , Correia J , Pernencar S , Soares F , Morais J
Published: October 2019

Background

The use of intravenous enoxaparin (LBWH) in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) was upgraded in the latest European Guidelines to a class IIa recommendation.

Purpose

The authors aim to compare safety and prognostic impact of LMWH versus unfractionated heparin (UFH) use in STEMI patients undergoing primary PCI.

Methods

Retrospective study of 3875 STEMI patients who underwent pPCI between October 2010 and September 2017 and were included in a national multicenter registry. Group A consisted of patients managed only with LMWH, and Group B patients were treated with UFH regardless of eventual LMWH associated exposure. The groups were compared according to their demographic, clinical and laboratory characteristics. The primary endpoint (PE) results from a composite which included: procedural failure (pPCI failure or bailout use of GPIIb/IIIa inhibitors), in-hospital mortality, re-infarction or major bleeding (according to the registry criteria). The secondary endpoint (SE) included: in-hospital major bleeding, need for red blood cell transfusion, or haemoglobin drop ≥2g/dL. A 1:1 propensity score (PS) analysis was performed according to demographic variables, medical history and previous medication, physical examination, electrocardiogram characteristics and left ventricular function, matching 1558 of the 3875 patients for later comparison between groups.

Results

Overall, Group A included 1083 (27.9%) and Group B 2792 (72.1%) patients. The mean age was 63±14 years, and 33.5% of the cohort were female. Despite the baseline characteristics heterogeneity between groups, this phenomenon was not observed after PS matching. The PE was more frequent in Group A, without reaching statistical relevance (15.6% vs 13.3%, p=0.07). The SE was superior in Group A (34.4 vs 29.4%, p=0.01). According to the PS matching analysis, there were no differences beetween groups in terms of the PE (13.9% vs 12.0%, p=0.28), while the SE kept more frequent among Group A (34.9% vs 28.5%, p=0.02) [Figure].

Propensity score: group comparison

Conclusion

In this study based on a national multicentric registry of STEMI patients, the use of LMWH was not associated with better in-hospital prognosis in terms of major cardiovascular events and was related with higher rates of bleeding related events in the scenario of pPCI, compared to UFH. According to these results, further studies are required to support the widespread use of LMWH in this clinical scenario.
P3126Immediate versus delayed revascularization in patients with transient ST-elevation myocardial infarction: 1-year follow-up of the randomized clinical TRANSIENT trial
Authors: Janssens G N , Van Der Hoeven N W , Lemkes J S , Everaars H , Van De Ven P , Marques K M J , Nap A , Van Leeuwen M A H , Appelman Y E A , Brinckman S L , Timmer J R , Meuwissen M , Van Der Weerdt A , Nijveldt R , Van Royen N
Published: October 2019

Background

Up to 24% of acute coronary syndrome patients present with ST-elevation but show complete resolution of ST-elevation and symptoms before revascularization. The current guidelines do not clearly state whether these transient ST-elevation myocardial infarction (TSTEMI) patients should be treated with a ST-elevation myocardial infarction (STEMI)-like or a non-STEMI-like invasive approach.

Purpose

The aim of the present study is to determine the effect of an immediate versus a delayed invasive strategy on infarct size measured by 4-month cardiac magnetic resonance imaging (CMR) and clinical outcome up to one year.

Methods

In this multicenter trial, 142 TSTEMI patients were randomized 1:1 to either an immediate or a delayed intervention. CMR was performed at four days and at 4-month follow-up to assess infarct size and myocardial function. Clinical follow-up was performed at four months and one year.

Results

Both in the immediate (0.4 h) and the delayed invasive group (22.7 h) CMR-derived infarct size at four months was very small and left ventricular function was good. In addition, major adverse cardiac events and all-cause mortality at one year were low and not different between both groups (table 1).

CMR and clinical outcomes up to one year Outcome Immediate invasive group (n=70) Delayed invasive group (n=72) p-value Myocardial infarct size (% of LV), median (IQR) 0.4 (0.0–3.5) 0.4 (0.0–2.5) 0.79 LVEF (%), mean ± SD 59.9±5.4 59.3±6.5 0.63 LVEF recovery (%), mean ± SD 2.2±5.4 1.7±5.3 0.66 MVO present, No. (%) 0 (0.0) 1 (1.9) 0.50 MACE (death, reinfarction, target lesion revascularization), No. (%) 3 (4.4) 4 (5.7) 1.00 Death from any cause, No. (%) 0 (0.0) 3 (4.3) 0.24 Reinfarction, No. (%) 2 (3.0) 1 (1.4) 0.62 Target lesion revascularization, No. (%) 2 (3.0) 1 (1.4) 0.62 Definite stent thrombosis, No. (%) 1 (1.5) 1 (1.4) 1.00 Abbreviations: IQR, interquartile range; LV, left ventricle; LVEF, left ventricle ejection fraction; MACE, major adverse cardiac events; MVO, microvascular obstruction; NA, not applicable; SD, standard deviation.

Conclusions

We demonstrated that patients with TSTEMI have limited infarct size and preserved left ventricular function and that an immediate or delayed approach has no effect on clinical outcome up to one year. Therefore, patients with TSTEMI can be treated with both an immediate or a delayed invasive strategy with similar outcome. These findings extend our current knowledge about the optimal timing of coronary intervention in patients with TSTEMI and complement the guidelines.

Acknowledgement/Funding

AstraZeneca, Biotronik
P3127Optimal revascularization strategy in non-ST-segment elevation myocardial infarction with multivessel coronary artery disease: staged vs. one-time vs. culprit-only revascularization
Authors: Kim M , Ahn Y , Jeong M H , Sim D S , Hong Y J , Kim J H , Ahn T H , Seung K B , Kim H S , Gwon H C , Chae S C , Hur S H , Cha K S
Published: October 2019

Background/Introduction

Although optimal revascularization strategy in patients with ST-segment elevation myocardial infarction with multivessel coronary artery disease (MVD) was well established, there are few studies which investigated optimal revascularization strategy in non-ST-segment elevation myocardial infarction (NSTEM) with MVD.

Purpose

We investigated 2-year clinical outcomes according to strategy of revascularization in patients with NSTEMI and MVD.

Methods

Between November 2011 and October 2015, a total of 2474 patients with NSTEMI and MVD who underwent successful percutaneous coronary intervention were analyzed from the Korea Acute Myocardial Infarction Registry-National Institute of Health (staged 308, one-time 1043 and culprit-only 1123 patients). We did not include patients with left main disease and cardiogenic shock. Primary endpoint was major adverse cardiac events (MACE: the composite of cardiac death, myocardial infarction [MI] or target-vessel revascularization [TVR]) during 2-year follow-up (median 737 days [interquartile range 705–764]). We also analyzed the of all-cause mortality, stroke and non-TVR.

Results

Baseline characteristics such as age, gender, and prevalence of atherosclerotic risk factors between multivessel revascularization (MVR; staged or one-time revascularization) and CVR were similar. There was also no difference in symptom to balloon time in 2 groups. MACE occurred in 305 patients (12.3%) during 2-year follow-up. MVR could reduce incidence of MACE (10.2% vs. 14.9%; adjusted hazard ratio [HR] 1.50 for CVR, 95% confidence interval [CI] 1.20–1.88, p<0.001), all-cause death (8.4% vs. 12.1%; adjusted HR 1.45 for CVR, 95% CI 1.13–1.87, p=0.003) and non-TVR (1,9% vs. 7.0%; adjusted HR 3.99 for CVR, 95% CI 2.55–6.27, p<0.001). There was no difference in incidence of stroke between MVR and CVR. We also analyzed same analysis between staged and one-time revascularization. Complete revascularization was more achieved in one-time revascularization group compared to staged revascularization group (62.0% vs. 76.1%, p<0.001). In multivariate Cox-regression analysis, staged revascularization was not associated with improved clinical outcomes in terms of MACE (HR 0.74, 95% CI 0.50–1.09, p=0.126), all-cause death (HR 1.07, 95% CI 0.69–1.68, p=0.759), stroke (HR 1.75, 95% CI 0.68–4.52, p=0.245) and non-TVR (HR 2.56, 95% CI 0.75–8.68, p=0.132). Analysis by propensity score matching and inverse probability of treatment weighting did not significantly affect the results.

Conclusions

MVR reduced 2-year adverse cardiac events in patients with NSTEMI and MVD compared to CVR. However, staged revascularization was not superior to one-time revascularization for reducing MACE among NSTEMI patients with MVD who received MVR.
P3136Percutaneous aspiration procedure as an adjunct to transvenous lead extraction procedures in patients with large lead vegetations
Authors: Starck C T , Schaerf R H M , Breitenstein A , Steffel J , Najibi S , Conrad J , Eulert-Grehn J J , Lanmueller P , Falk V
Published: October 2019

Background

Patients with systemic CIED (Cardiac implantable electronic device) infection with large lead vegetations are a clinical challenge and carry a high operative risk. In three lead extraction centers a treatment strategy with minimal-invasive percutaneous aspiration of vegetations and subsequent transvenous lead extraction was established. The results of this concept were evaluated with regard to safety and efficacy in this retrospective multi-center study.

Methods

Between June 2015 and December 2018 we performed combined percutaneous aspiration procedures and transvenous lead extractions in 107 patients with 262 targeted leads (179 pacemaker leads, 83 ICD leads) for extraction. Mean lead vegetation size in preoperative echocardiography was 30.6±13.3 mm. Mean lead implant duration were 82.8 (1–254) months. The aspiration system is based on a veno-venous extracorporeal circuit with an in-line filter and a specialized venous drainage cannula.

Results

Complete procedural success of the percutaneous aspiration procedure was 94.4% (n=101), partial success was achieved in 4.7% (n=5). Three complications (2.8%) related to the aspiration procedure were encountered. In the concomitantly performed transvenous lead extraction procedures complete procedural success per targeted lead was 99.2% (n=260). 30 day mortality was 2.8% (n=3).

Conclusion

The minimal-invasive percutaneous aspiration procedure proved to be safe and effective. It facilitated the subsequent transvenous lead extraction procedure, avoids septic embolization into the pulmonary circulation and abolished the need for open surgical extraction in this high-risk patient group.
P3347Pre-hospital time and 30-day mortality in patients with presumed heart conditions or dyspnea: a registry-based cohort study of patients requiring a highest priority emergency medical response
Authors: Mills E H A , Aasbjerg K , Hansen S M , Ringgren K B , Dahl M , Rasmussen B S , Torp-Pedersen C , Soegaard P , Kragholm K
Published: October 2019

Introduction

Centralization of emergency care is expected to increase average pre-hospital time for patients, leading to concerns about possible adverse outcomes for patients. Prior studies have found increased mortality for patients with prolonged transport following acute myocardial infarction.

Purpose

Examine the association between total pre-hospital time (from dispatch to hospital arrival) and mortality for patients, depending on the condition presumed by the emergency dispatcher (presumed heart condition, dyspnea or non-specific medial conditions).

Methods

Pre-hospital registry data from a Danish region from 2006–2012 was used. This contained information on ambulance dispatch priority, ambulance times, and patient condition, as well if procedures consistent with cardiac arrest (CPR or shock) were performed. We included patients with both highest priority dispatch and transport to the hospital. Linkage to nationwide registries of hospital admissions, comorbidities and mortality was performed. Logistic regression was used for analysis.

Results

95% of total pre-hospital times were below 84 minutes. 30-day mortality was highest among patients with dyspnea (36.6%). Compared to pre-hospital times of 0–30 min, odds ratios of 30-day mortality for times >60 min were: for presumed heart conditions 0.54 [95% CI 0.38–0.77] (p<0.001), for dyspnea 0.98 [95% CI 0.65–1.47] and for other medical conditions 1.14 [95% CI 0.98–1.32]

Patient characteristics and outcomes according to the presumed aetiology of the priority 1 emergency dispatch Presumed heart condition Dyspnea Other medical conditions N 1836 1101 11538 Age, median {IQR} 66.4 {55.3, 76.8} 70.5 {56.8, 80.8} 61.5 {40.3, 75.8} Male, n (%) 1194 (65.0) 585 (53.1) 6172 (53.5) 10-year Charlson comorbidity index score ≥3, n (%) 744 (40.5) 613 (55.7) 4311 (37.6) Response time, median {IQR} 9 {5, 13} 9 {5, 13} 8 {5, 13} Total pre-hospital time, median {IQR} 49{37,61} 45{34, 58} 46{34,58} Cardiac arrest procedures during transport, n (%) 266 (14.5) 133 (12.1) 844 (7.3) Cardiovascular diagnosis (DI00-DI99), n (%) 962 (52.4) 282 (25.6) 3285 (28.5) Respiratory diagnosis (DJ00-DJ99), n (%) 82 (4.5) 430 (39.1) 1036 (9.0) 1-day mortality, n (%) 289 (15.7) 225 (20.4) 1311 (11.4) 30-day mortality, n (%) 402 (21.9) 403 (36.6) 2264 (19.6)

Logistic regression, 30-day mortality

Conclusion

No overall association between total pre-hospital time and mortality, however for presumed heart conditions longer times may improve survival.

Acknowledgement/Funding

Program for clinical research infrastructure (PROCRIN) established by the Lundbeck and Novo Nordisk foundations & The Danish Heart Foundation
P3350Design of a multicenter, open-label, randomized controlled trial: effects of intensive systolic blood pressure lowering treatment in reducing risk of vascular events (ESPRIT)
Authors: Liu J , Li J , Huang X H
Published: October 2019

Background

Patients with cardiovascular diseases (CVD) are at high risk for recurrent major cardiovascular events. Effective public health strategies to lower blood pressure (BP) are necessary to reduce risk of cardiovascular disease. However, substantial uncertainty remains about the optimal target level to lower BP in patients with cardiovascular disease.

Purpose

To assess the effects on the incidence of major cardiovascular events in patients with CVD during the scheduled treatment period of greater reduction in blood pressure with a systolic BP (SBP) target <120 mmHg versus <140 mmHg.

Methods

This study is a multicenter, open-label, randomized controlled trial comparing two strategies for lowering SBP: lowering SBP to the standard target of <140 mmHg; and lowering BP to a more intensive target of <120 mmHg. This study will enroll 12,000 Chinese participants from 100–200 hospitals, follow-up for about 3 years. We will include participants aged ≥50 years old with SBP ≥130 mmHg, having a history of vascular disease (including myocardial infarction, percutaneous coronary intervention, coronary artery bypass grafting, carotid endarterectomy or carotid stenting, peripheral artery disease with revascularization, abdominal aortic aneurysm ≥5 cm with repair) or stroke. The primary outcome is the first occurrence of major cardiovascular events defined as a composite of myocardial infarction, stroke, coronary or non-coronary revascularization events, and cardiovascular death. Secondary outcomes include the components of the primary composite outcome, hospitalized heart failure and all cause of death and non-cardiovascular outcomes (kidney disease and cognitive outcomes).

Results

Regarding the results, we hypothesize that comparing with SBP target of <140 mmHg, more intensive SBP target of <120 mmHg can further reduce the occurrence of cardiovascular events in CVD patients with elevated blood pressure.

Conclusion

This study can provide reliable evaluation on whether more intensive SBP target of <120 mmHg is more desirable than SBP target of <140 mmHg in CVD patients with elevated blood pressure.
P3356Antiarrhythmic therapy with amiodarone decreases the uptake of 82-Rubidium-PET: studies in a rodent model
Authors: Bentsen S , Jensen J K , Ripa R , Hasbak P , Kjaer A
Published: October 2019

Introduction

Myocardial perfusion imaging using positron emission tomography (PET) with 82Rubidium (82Rb) is used as a standard clinical examination. 82Rb-PET provides important information for the correct diagnosis and aids in prognostic risk assessment in patients with ischemic heart disease. 82Rb enters the myocardial cells by active transport of the sodium/potassium adenosine triphosphate transporter. Some antiarrhythmic drugs inhibits sodium/potassium adenosine triphosphate transporter.

Purpose

To determent if the uptake of 82Rb-PET using standard uptake value (SUV) is affected by administration of antiarrhythmic drugs.

Methods

Twenty-one Sprague-Dawley rats were baseline PET/CT scanned with 82Rb, using a Siemens preclinical PET/CT Inveon MM system and a Cardiogen-82 Rb generator. After baseline scan, the rats were divided into three groups. One control group without any treatment, and two received treatment with either orally administered Metoprolol 50mg/kg/24h or orally administered Amiodarone 120mg/kg/24h for seven days. All three groups were again PET/CT scanned with 82Rb-PET after the last administration on day seven. Data are presented as mean ±SEM.

Results

In the control group, there was no difference in mean SUV in the heart from day one to day seven (SUVmean 3.47±0.11 vs 3.45±0.35 p=0.97). In the group treated with metoprolol, likewise there was no difference in mean SUV in the heart from day one to day seven (SUVmean 3.87±0.13 vs 4.4±0.21 p=0.096). In contrast, in the group treated with amiodarone there was a significant difference in mean SUV from day one to day seven (SUVmean 4.14±0.15 vs 3.38±0.18 p=0.001). In all three groups there was no difference in mean SUV from day one to day seven in the liver and kidney.

Conclusions

The antiarrhythmic drug amiodarone had a clear impact on SUVmean in the heart. To the best of our knowledge, this is the first time it has been shown, that amiodarone lowers the SUV in 82Rb-PET in the heart. Amiodarone therefore seems to change to uptake of 82Rb in the myocyte. This could potentially influence the calculation to estimate absolute flow through the coronary arteries and lead to wrong conclusions regarding myocardial perfusion in patients treated with amiodarone. Further studies are needed to characterize the mechanism and to confirm the effect clinically.
P3357Reproducibility of myocardial flow reserve estimation using Rubidium-82 PET/CT scans in healthy, young volunteers: comparison of three commercially available software packages
Authors: Byrne C , Kjaer A , Olsen N E , Forman J L , Hasbak P
Published: October 2019

Background

The use of myocardial blood flow (MBF) reserve assessed with cardiac positron emission computed tomography (PET/CT) is well established and contain important prognostic information e.g. in patients with ischaemic heart disease. However, perfusion data must be interpreted under consideration of the limitations of the method. It has previously been concluded that software specific age and sex matched normal values for MBF reserve should be used as reference. Furthermore, reproducibility between scans seems to vary more in persons with higher risk of cardiovascular disease than in those with no risk factors. Comparison between scans has previously been conducted using dipyridamole as a stressor. However, no former studies have addressed this using adenosine as stressor for 82Rb-PET/CT in a combined study of scan reproducibility and software comparison.

Purpose

The aim of this study was to investigate reproducibility of rest- and adenosine stress 82Rb-PET/CT estimated MBF reserve in healthy young volunteers between two scans analysed with three commercially available software packages.

Methods

Forty healthy young volunteers completed two 82Rb-PET/CT rest- and adenosine stress scans obtaining myocardial blood flow (MBF) and MBF reserve, syngo MBF, Quantitative Gated SPECT (QGS) and Corridor4DM (4DM) were used for analyses.

Results

Fifty percent were men and mean (±SD) age was 24±4 years. Varying reproducibility of MBF reserve between scans was found for the different software packages. MBF reserve with syngo.MBF (Figure 1A): mean difference (95% CI) 0.26 (−0.03 to 0.54), P=0.07, limits of agreement: −1.43 to 1.95, MBF reserve with QGS (Figure 1B): mean difference (95% CI) 0.19 (−0.08 to 0.46), P=0.15, limits of agreement: −1.38 to 1.76 and MBF reserve with 4DM (Figure 1C): mean difference (95% CI) 0.08 (−0.17 to 0.34), P=0.50, limits of agreement: −1.37 to 1.53. Significantly higher MBF reserve was measured with 4DM (mean±SD: 4.00±0.96) compared to syngo.MBF (mean±SD 3.75±0.91, P<0.001) and QGS (mean±SD 3.75±0.89, P<0.0001), whereas concordance between MBF reserve measured by syngo.MBF and QGS was high (P=0.87).

Figure 1

Conclusions

All software packages identified the participants with flow values in the high end of the normal range, as expected for healthy volunteers. Varying reproducibility of MBF reserve was found between scans for the different software packages and 4DM seemed to have the highest inter-scan reproducibility. Concordance between MBF reserve measures was high between syngo.MBF and QGS whereas higher MBF reserve measures was conducted from 4DM in comparison with the two other software packages. Our results suggest that MBF analysed with syngo.MBF and QGS may be mutually comparable but that 4DM may be preferred for analyses due to possibly higher scan to scan reproducibility.
P3366Increased left ventricular remodelling index in paradoxical low-flow severe aortic stenosis with preserved left ventricular ejection fraction compared to normal-flow
Authors: Ngiam N , Chew N , Sim H W , Tan Y Q B , Sia C H , Kong W K F , Yeo T C , Poh K K
Published: October 2019

Background

Left Ventricular Remodelling Index (LVRI) has been demonstrated to be able to reliably discriminate between an athlete's heart and pathological LV remodelling. Patients with paradoxical low-flow severe aortic stenosis (LF AS) despite preserved left ventricular ejection fraction (LVEF) are a distinct group from normal-flow (NF) with poorer prognosis, more concentric hypertrophy and smaller LV cavities.

Purpose

We compared LVRI in LF compared to NF AS and examined clinical outcomes.

Methods

We studied consecutive patients with index echocardiographic diagnosis of severe AS (aortic valve area<1cm2) with preserved LVEF (>50%). LVRI was determined by the ratio of LV mass to the end-diastolic volume.

Results

Of the 450 patients studied, 149 (33.1%) were LF. There were no significant differences in baseline clinical profile of patients between LF and NF. LVRI was significantly higher in patients with LF compared to NF (2.27±0.68 vs 1.85±0.53 g/ml, p<0.001). Patients with high LVRI (>1.56 g/ml) had poorer clinical outcomes in terms of mortality (log-rank 9.18, p=0.002) and admissions for cardiac failure (log-rank 7.61, p=0.006).

Low-flow (n=149) Normal-flow (n=301) Mean difference/Odds Ratio (95% CI) p-value Age (years) 73.5 (±12.8) 71.0 (±13.1) 2.5 (−0.1 to 5.1) 0.053 Body Mass Index (g/m2) 24.6 (±5.6) 24.7 (±5.3) −0.1 (−1.2 to 1.1) 0.877 Gender (male) 49 (32.9%) 125 (41.5%) 0.7 (0.5 to 1.1) 0.076 Hypertension 100 (67.1%) 195 (64.8%) 1.1 (0.7 to 1.7) 0.624 Diabetes 57 (38.3%) 100 (33.2%) 1.2 (0.8 to 1.9) 0.295 Hyperlipidaemia 79 (53.0%) 147 (49.0%) 1.2 (0.8 to 1.7) 0.425 End-diastolic volume (ml) 72.3 (±18.9) 112.6 (±26.3) −40.2 (−44.9 to −35.5) <0.001 Left ventricular ejection fraction (%) 66.0 (±7.9) 67.4 (±7.1) −1.4 (−2.9 to 0.2) 0.077 Left ventricular mass index (g/m2) 99.7 (±33.0) 126.8 (±37.4) −27.2 (−34.8 to −19.6) <0.001 Transaortic mean pressure gradient (mmHg) 32.2 (±17.4) 37.1 (±19.9) −4.9 (−8.6 to −1.1) 0.011 Aortic valve area (cm2) 0.78 (±0.16) 0.79 (±0.17) 0.1 (−0.2 to 0.1) 0.635 Stroke volume index (ml/m2) 28.6 (±5.6) 46.9 (±9.8) −18.3 (−20.0 to −16.6) <0.001 Left ventricular remodelling index (LVRI, g/ml) 2.27 (±0.68) 1.85 (±0.53) 0.42 (0.31 to 0.54) <0.001

LVRI in LF versus NF AS

Conclusion

Pathological LV remodelling as evidenced by increased LVRI was more common in LF compared to NF AS. Patients with increased LVRI also had worse clinical outcomes.

Acknowledgement/Funding

None
P3370Prevalence of right ventricular dysfunction according to different parameters: basal and one year after transcatheter aortic valve implantation
Authors: Pardo Sanz A , Santoro C , Hinojar R , Rajjoub E , Pascual M , Salido L , Gonzalez A , Garcia A , Jimenez J J , Casas E , Abellas M , Hernandez S , Hernandez R , Zamorano J L , Fernandez-Golfin C
Published: October 2019

Background

Right ventricle (RV) is not often specifically studied in patients with severe aortic stenosis (AS). It's difficult to find the correct tool to assess RV function with echocardiographic parameters, and the percentage of patients with dysfunction may vary depending on the parameter that we use.

The aim of the study was to evaluate the prevalence of RV dysfunction basal and one year after transcatheter aortic valve implantation (TAVI), according to different parameters.

Methods

Consecutive patients with severe AS undergoing TAVI from January 2016 to July 2017 were included. RV anatomical and functional parameters were analyzed according to ESC and ASE guidelines. RV dysfunction was assessed using tricuspid annular plane systolic excursion (TAPSE) <17 mm, fractional area change <35%, systolic movement of the RV lateral wall by tissue Doppler imaging (RV-S'TDI) <9.5 cm/s, global longitudinal (RV-GLS) and free wall strain (RV-FWS) using as cutting point [20]. Pre procedure echo, immediate post procedure and 1 year echo were analyzed. Statistical analysis was performed using SSPS version 22.

Results

The final study population consisted of 78 patients (115 patients were included, 37 were excluded due to suboptimal acoustic window for RV anatomical and functional evaluation), mean age 83.73±6.31 year-old, 38.2% females. We analyzed the percentages of RV dysfunction according to the different parameters evaluated before and in the control one year after. They are shown in Figure 1.

Prevalence of RV dysfunction

Conclusions

The presence of RV dysfunction in patients with severe AS is higher than expected Our data suggest that RV function improve one year after TAVI, in terms of a reduction in the number of patients with dysfunction. The assessment of RV function is difficult, and there is no agreement on what tools are more accurate and useful. RV strain seems to be the most sensible parameter to assess RV function in patients with AS undergoing TAVI. Impact of these measurements in patients management needs further evaluation.
P3381Quantification of hypo-attenuated leaflet thickening after transcatheter aortic valve implantation - clinical relevance of HALT volume
Authors: Karady J , Apor A , Nagy A I , Kolossvary M , Szilveszter B , Simon J , Molnar L , Bartykowszki A , Jermendy A L , Panajotu A L , Suhai F I , Varga A L , Rajani R , Maurovich-Horvat P , Merkely B
Published: October 2019

Background

Hypo-attenuated leaflet thickening (HALT) is a recently recognized phenomenon following transcatheter aortic valve implantation (TAVI) and there is no consensus over the standardized assessment of HALT and its clinical relevance is poorly understood. We sought to determine the predictors and clinical significance of HALT volume.

Methods

Patients, who previously underwent TAVI between 2011 and 2016 were prospectively enrolled in the RETORIC (Rule out Transcatheter Aortic Valve Thrombosis with Post Implantation Computed Tomography) study, a single-center observational study. At inclusion cardiac computed tomography angiography (CTA), transthoracic echocardiography (TTE) and brain magnetic resonance imaging (MRI) was performed. HALT was volumetrically quantified on cardiac CTA images by segmenting the inner volume of the TAVI frame at the level of the leaflets and applying a threshold of −200 to 200 Hounsfield units. We evaluated the clinical predictors of HALT volume, and its association with ischemic brain MRI lesions (recent and chronic large vessel ischemic focuses, microbleed/microembolization, white matter or small vessel disease) and all-cause mortality.

Results

In total, we analyzed 111 patients with CoreValve bioprosthesis (56.7% female, mean age 80.3±7.4 years). A median of 19 [IQR: 11–29] months passed between TAVI procedure and enrollment. The mean HALT volume was 111.0±163.4 mm3. Current malignant disease, prosthesis implantation depth measured on CTA images acquired at inclusion, and aortic mean gradient and aortic valve area evaluated on TTE images at inclusion predicted HALT volume by univariate analysis (all p<0.05). After multivariate adjustment, aortic mean gradient remained a significant predictor of HALT volume (beta-coefficient: 11.5, 95% CI: 5.0–18.0; p<0.001). HALT volume was not associated with ischemic brain MRI lesions (all p>0.05) and did not predict all-cause mortality (median follow-up: 20 months [IQR: 18–23]; HR: 1.0; 95% CI: 1.0–1.0; p=0.15).

Volumetric quantification of HALT.

Conclusion

Aortic mean gradient was the only predictor independently associated with HALT volume. Our results suggest that TAVI valve function is negatively affected by HALT volume, however, we found no association of HALT volume with cerebrovascular ischemic lesions or increased risk for all-cause mortality.
P3400Definition of extremely high cardiovascular risk in patients after acute myocardial infarction - Data from the TERCET Registry
Authors: Dyrbus K , Gasior M , Desperak P , Osadnik T , Banach M
Published: October 2019

Background

The latest guidelines from the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology (ACE) introduced a new “ultra-high risk” category of patients, for whom a low-density lipoprotein cholesterol (LDL-C) level <55 mg/dL (1.4 mmol/L) is advised.

Purpose

Therefore we aimed at identification of the risk factors in patients after acute myocardial infarction (MI), which increased the risk most, and might help to define the group of individuals at extremely high cardiovascular (CV) risk.

Methods

We analyzed consecutive patients included in the TERCET Registry admitted to the Polish tertiary cardiovascular centre due to MI between 2006 and 2018. According to the guidelines of the European Society of Cardiology (ESC), all patients included in the analysis are considered as of very high CV risk. All patients included in the registry underwent coronary angiography during the hospital stay. On the basis of multivariate analysis, we determined the subgroup of patients with the most unfavourable 12-month outcome (all-cause mortality).

Results

Finally, 4,562 patients admitted due to STEMI or NSTEMI and discharged from our centre were included in the analysis. According to the results of multivariate analysis performed with stepwise backward regression model, the following risk factors in patients after MI: LVEF<35% (odds ratio [OR]=3.83, 95% confidence interval [CI]: 3.14–4.67), age>75 years (OR=1.91, 95% CI: 1.55–2.35), lack of PCI of culprit vessel (OR=1.66, 95% CI: 1.26–2.20), multivessel CAD (OR=1.60, 95% CI: 1.30–1.99), atrial fibrillation (OR=1.53, 95% CI: 1.21–1.94), diabetes mellitus (OR=1.34, 95% CI: 1.11–1.64), increased LDL-C level (OR=1.09 per 1 mmol/L, 95% CI: 1.01–1.19) and increased creatinine level (OR=1.04 per 10 μmol/L, 95% CI: 1.04–1.05), might help to define the group of patients at extremely-high cardiovascular risk (all p<0.05). The aggregate summary of risk factors associated with extremely high risk is presented in the attached Figure.

Next, the effect of the combination of the aforementioned risk factors will be investigated, and SCORE applied for patients in secondary prevention after MI will be prepared.

Multivariate analysis results

Conclusions

To our knowledge, the presented study is the first such an analysis conducted on the population of patients after myocardial infarction gathered in the registry of secondary cardiovascular prevention. In patients after MI, potential risk factors were identified that might help to define the group of patients at ultra-high/extremely-high risk, what might contribute to significantly higher 12-month mortality.

Acknowledgement/Funding

None