bluuebunny/crossref_metadata_2025 huggingface dataset:
3333Contemporary mortality rates in myocardial infarction patients in Sweden: a tale of two registries
Authors: Siverskog J , Janzon M , Levin L.-Å , Alfredsson J , Henriksson M
Published: October 2019

Background

Sweden has contributed to the understanding of the long-term prognosis after myocardial infarction (MI) utilising the quality registry SWEDEHEART, including patients admitted to heart intensive care, and the National Patient Registry (PAR), based on administrative records for Swedish hospitals. As registration procedures differ between the registries, and not all MI patients are admitted to heart intensive care, MI patients identified in SWEDEHEART and PAR, respectively, will yield different cohorts of patients. This may result in different epidemiological research findings regarding prognosis after MI.

Purpose

To study MI populations identified in SWEDEHEART and PAR, respectively, and investigate potential differences in mortality outcome.

Methods

Patients hospitalised with an MI primary diagnosis (ICD-10 I21) between 2002 and 2015 were identified using SWEDEHEART and PAR. The analysis time started at the date of hospital admission and survivors were followed for 365 days. Kaplan-Meier analysis was used to estimate survival by cohort category controlling for age and gender.

Results

Excluding cases with invalid data (n=1,905), 225,612 and 282,118 SWEDEHEART and PAR patients, respectively, were identified. We found 213,367 patients in both SWEDEHEART and PAR, whereas 12,245 and 68,751 patients were unique to SWEDEHEART and PAR, respectively. The one-year survival probability after MI in the SWEDEHEART population was 0.841, compared to 0.788 in PAR (Figure). This discrepancy can be explained by high mortality among patients not covered by SWEDEHEART and persists after controlling for age and gender (Table). To what extent differences in registration procedures and other patient characteristics can explain the mortality difference is an area for further research.

One-year survival by age and gender Age ± 1 year Male Female PAR S.H. Diff. PAR S.H. Diff. 65 0.922 0.936 0.015 0.919 0.936 0.017 70 0.893 0.909 0.016 0.889 0.908 0.019 75 0.829 0.858 0.029 0.834 0.860 0.026 80 0.743 0.783 0.040 0.768 0.800 0.033 85 0.625 0.677 0.052 0.662 0.705 0.042

One-year survival after MI

Conclusion

Estimated one-year survival for MI patients differs by up to 5 percentage points depending on the registry used. Although further research is needed to fully understand these differences, epidemiological findings regarding MI prognosis should be interpreted in light of registry type used and population represented.

Acknowledgement/Funding

Region Östergötland
3335First-line coronary computed tomography predicts long-term clinical outcome in patients with Non-ST-segment elevation acute coronary syndrome - The VERDICT trial
Authors: Kofoed K F , Engstroem T , Sigvardsen P , Torp-Pedersen C , Linde J , Riis Hansen P , Holmvang L , Hofsten D , Elming H , Gislason G , Kelbaek H , Kober L
Published: October 2019

Background

In patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) coronary pathology may range from structurally normal vessels to severe coronary artery disease. Current guidelines recommend early invasive coronary angiography (ICA) for risk assessment and choice of treatment strategy.

Purpose

We tested the hypothesis that 1) a first-line coronary computed tomography angiography (CCTA) predicts long term clinical outcome in patients with NSTE-ACS and 2) adding ICA to CCTA does not improve prediction of cardiovascular events.

Methods

We included patients with NSTE-ACS confirmed by ischaemic ECG changes and/or elevated biomarkers of myocardial ischaemia, in whom both CCTA and ICA were feasible within 12 hours. According to the VERDICT study protocol (ClinicalTrials.gov number NCT02061891) patients were randomised 1:1 to evaluation within 12 hours (Very Early) or 48–72 hours (Standard). CCTA was conducted prior to ICA and patients with an event between tests were excluded. Based on CCTA and ICA, patients were categorized according to European Society of Cardiology (ESC) guidelines as having prognostic indication for coronary revascularization ESCprog (left main stenosis, proximal left anterior descending artery stenosis or multivessel disease) or no prognostic indication – ESCnon-prog. The primary endpoint was a combined endpoint of all-cause mortality, non-fatal recurrent myocardial infarction, hospital admission for refractory myocardial ischemia or hospital admission for left sided heart failure. Discrimination of 1.5-year outcomes was assessed by time-dependent area under the receiver operating characteristic curve (AUC).

Results

CCTA and ICA was conducted in 979 patients. During a median follow-up time of 4.2 (IQR 2.7–5.5) years the primary endpoint occurred in 209 (21.3%) patients. Patients with ESCprog as defined by CCTA had a hazard ratio of 1.53 (95% CI 1.16–2.03) for occurrence of the primary endpoint. AUC for the prediction of the primary endpoint by CCTA was 68.6 (95% CI: 62.7–74.5) as compared to 68.6 (95% CI: 62.8–74.5), when adding ICA to the model. Similar findings were noted in patients randomized to either Very Early or Standard treatment strategy.

Conclusions

Long-term risk assessment in patients with NSTE-ACS may be conducted using a first-line CCTA strategy and may thus potentially guide patient management. Adding invasive coronary angiography to CCTA does not improve risk assessment.

Acknowledgement/Funding

This study was funded by the Danish Agency for Science, Technology, and Innovation and the Danish Council for Strategic Research (grant no. 09–066994)
4034Distance from hospital as an early marker of outcomes in out of hospital cardiac arrest acute myocardial infarction survivors treated with endovascular mild therapeutic hypothermia
Authors: Hetclova D , Hutyra M , Precek J , Moravec O , Skala T , Sanak D , Adam T , Taborsky T
Published: October 2019

Background

The prediction of outcome in comatose patients after out of hospital cardiac arrest (OHCA) has major ethical and socioeconomic implications. At present, there is a lack of data comparing the predictive value from cardiac arrest localization to hospital distance in OHCA survivors treated with endovascular therapeutic hypothermia.

Methods

86 patients (64±14 years, 69 men) were evaluated after OHCA due to ventricular fibrillation (VF) during an acute myocardial infarction (MI). All patients (NSTEMI 28%, STEMI 72%) were indicated for urgent coronary angiography, echocardiography for left ventricular ejection fraction (LVEF) estimation using Simpson biplane formula and treated with mild therapeutic hypothermia (MTH) using intravascular temperature management to maintain target temperature (33 °C) for 24 hours. The Cerebral Performance Categories scale (CPC) was used as the outcome measure and was assessed 3 months post admission; a CPC of 3–5 was regarded as a poor outcome (n=45), and a CPC of 1–2 (n=41) as a good outcome.

Results

Distance to hospital was significantly higher (p=0.0473) in patients with poor outcomes (CPC 3–5) after OHCA (37.5±4.5 km) compared with CPC 1–2 patients (27.1±4.4 km). No significant differences in return of spontaneous circulation time (21; 10.5–47.5 95th percentile vs. 23; 10.0–50.0, p=0.738), lactate (7.8; 4.5–12.4 vs. 8.4; 5.4–13.5, p=0.54), LVEF (40; 22–50 vs. 40; 21–62%, p=0.208), peak cardiac troponin T (1.5; 0.08–10.00 vs. 0.64; 0.04–5.28 μg/L, p=0.078), NSE (29.2; 15.7–54.9 vs. 25.8; 13.6–52.3 μg/L, p=0.26) and S100-B (0.17; 0.09–1.69 vs. 0.19; 0.04–1.14 μg/L, p=0.734) were found in CPC 3–5 and CPC 1–2 groups comparison. Using an optimal cut-off value ≥33 km calculated from the receiver operating characteristic curve (area under curve = 0.62; p=0.004), the sensitivity of predicting survival with poor neurological outcome was 61% and the specificity was 62%.

Conclusions

In patients after OHCA for VF during MI, distance from cardiac arrest localization to hospital gives reliable and on return of spontaneous circulation time independent prognostic information concerning outcome after cardiopulmonary resuscitation.

Acknowledgement/Funding

Grant support FNOL RIV 87-85
4037Nurse counseling of patients with atrial fibrillation to improve compliance to oral anticoagulation
Authors: Chilian-Hof R , Schnupp S , Mahnkopf C , Brachmann J , Kleinecke C
Published: October 2019

Background

Atrial fibrillation (AF) is the most frequent arrhythmia with a prevalence of 1%–2% in the general population. Oral anticoagulation (OAC) is state-of-the art for preventions of thromboembolic events, in particular ischemic stroke, in patients with atrial fibrillation. Despite its proven benefit, numerous studies have documented under use of OAC for a variety of reasons.

Purpose

To establish a program of nurse counseling in patient with atrial fibrillation and treatment with oral anticoagulation. The program is designed to improve patients satisfaction, compliance to OAC, prevention of medication errors, ischemic and bleeding events.

Methods

Patients with atrial fibrillation and treatment with oral anticoagulation were prospectively identified at the department of cardiology of our clinic. They received a 30 minutes nurse counseling about oral anticoagulation during the hospital stay and another 30 minutes telephone counseling 3 months after inclusion. Furthermore, they received a brochure to inform about atrial fibrillation, oral anticoagulation and methods to improve medication compliance. Demographic characteristics with stroke and bleeding risk (CHA2DS2-VASc and HAS-BLED scores), as well as procedural data were systematically assessed in a predefined standardized way and captured in a dedicated database.

Results

Between June 2017 and January 2018, a total of 617 patients (female gender: 43.1%) with atrial fibrillation and oral anticoagulation received nurse counseling. Demographic and follow-up data of 204 patients (female gender: 85/204 (41.7%); mean age 69.7±17.3, CHA2DS2-VASc score 4.2±1.7, HAS-BLED score 2.8±0.37) were assessed in a dedicated database. Indication for OAC was paroxysmal and persistent/permanent AF in 110/204 (53.9%), 93/204 (45.6%) and others 17 (8.3%), respectively. 33/2014 (16.2%) were treated with vitamin K antagonists, and 172/204 (84.3%) with non-vitamin K antagonists. After a follow-up of 0.46±2.9 years and 187 patients-years the rates of cardiovascular death, major bleeding events and all-cause stroke and TIA were 1.07%, 2.14% and 1.61% per 100 patient-years.

Conclusion

Nurse counseling in patients with atrial fibrillation and treatment with oral anticoagulation has been established at the REGIOMED clinics, Germany. Its effectiveness in terms of quality of live, medication complications and cardiovascular events has to be proven in a randomised trial.

Acknowledgement/Funding

Daichi-Sankyo
4069From first in man transcatheter aortic valve implantation, a 15-year experience
Authors: Avinee G , Durand E , Levesque T , Litzler P Y , Dacher J N , Bauer F , Tron C , Cribier A , Eltchaninoff H
Published: October 2019

Background

Since the first-in-man transcatheter aortic valve implantation (TAVI) performed in 2002, the number of procedures has dramatically increased. However, long-term data regarding outcome and valve durability remain poor.

Purpose

We aimed to evaluate the evolution of 30-day outcomes over years and long-term mortality and valve durability after TAVI.

Methods

All consecutive patients presenting with severe symptomatic aortic stenosis treated by TAVI in our center were included prospectively. Clinical and echocardiographic follow-up was performed at 30 days and annually thereafter. Survival curves were constructed using Kaplan-Meier analysis. We also evaluated valve durability according to the European standardized definition of structural valve deterioration.

Results

Between 2002 and 2018, 1530 consecutive patients underwent TAVI including 1285 (84.0%) patients via a femoral approach. A balloon-expandable transcatheter heart valve was predominantly used (1421 patients; 92.9%). The annual transfemoral approach rate increased progressively to reach 93.3%. Age of patients remained stable over time with a global mean age of 83.7±6.5 years old. Logistic EuroSCORE decreased from 49.2±8.2% to 14.3±8.6% (p<0.0001). Thirty-day mortality dramatically decreased below 3% since 2015 and was 0% in 2018. Similarly, major vascular complications decreased from 50.0% in the first year to less than 1% since 2017 (p=0.001). The length of hospital-stay progressively shortened up to a median of 2 days in 2018. The Kaplan-Meier survival estimation was 82.3%, 60.3%, 33.0%; 11.7% and 8.9% respectively at 1, 3, 5, 8 and 10 years. On long-term follow-up the mean aortic gradient remained unchanged (Figure), and only five patients presented a severe prosthetic valve deterioration. Among them, four patients successfully benefited from a valve in valve TAVI procedure. The competing risk analysis at 10 years estimates risk for severe and moderate-or-severe valve deterioration of 1.9±0.9% and 4.3±1.3% respectively.

TEE mean transaortic gradient

Conclusions

Long-term (up to 10 years) follow-up of our large pioneer series of patients treated by TAVI shows a dramatic improvement of outcomes and no warning signs of valve deterioration suggesting very encouraging valve durability, using predominantly, a balloon expandable prosthesis. Further studies are warranted to study valve durability after TAVI before extension to lower risk patients.
4078Lipoprotein(a) and clinical outcomes in patients after revascularization of peripheral arteries
Authors: Tmoyan N A , Ezhov M V , Afanasieva O I , Klesareva E A , Afanasieva M I , Pokrovsky S N
Published: October 2019

Background

Randomized trials have proved the reduction of cardiovascular events due to LDL-cholesterol level decrease. However, despite high-intensity statin therapy, there is a residual risk, that could be associated with lipoprotein(a) [Lp(a)]. It has been shown that there is an association between elevated Lp(a) level and cardiovascular outcomes in patients with coronary heart disease. Data about the role of Lp(a) in the development of cardiovascular events after revascularization of peripheral arteries are scarce.

Purpose

To evaluate the relationship of Lp(a) level with cardiovascular outcomes after revascularization of carotid and lower limbs arteries.

Methods

The study included 258 patients with severe carotid and/or lower extremity artery disease, who underwent successful elective revascularization. The primary endpoint was the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. The secondary endpoint was the composite of transitory ischaemic attack, limb amputation, hospitalization for unstable angina, or revascularization surgery.

Results

During 36 months follow-up 29 (11%) primary and 113 (44%) secondary endpoints were registered. It was noted greater rate of primary (21 [8%] vs. 8 [3%]; hazard ratio [HR], 3.0; 95% confidence interval [CI] 1.5–6.3; p<0.01) and secondary endpoints (72 [28%] vs. 41 (16%], HR, 2.5; 95% CI 1.7–3.7; p<0.01) in patients with elevated Lp(a) level (≥30 mg/dl) compared to patients with Lp(a) <30 mg/dl (Picture). Multivariable-adjusted Cox regression analysis revealed that Lp(a) was independently associated with incidence of cardiovascular outcomes.

Conclusions

Patients with peripheral artery diseases have a high risk of cardiovascular events and the level of Lp(a) ≥30 mg/dl is an independent predictor of cardiovascular events in prospective 3-year follow-up after revascularization of carotid and lower limbs arteries.
4090Maximum standardized uptake value of pericardial fat for prediction of ventricular arrhythmias in patients with cardiac sarcoidosis
Authors: Ishii Y , Yufu K , Kira S , Miyoshi M , Abe I , Oniki T , Kondo H , Saito S , Fukui A , Okada N , Akioka H , Shinohara T , Teshima Y , Nakagawa M , Takahashi N
Published: October 2019

Background

Cardiac sarcoidosis is a cause of epicarditis and sustained life-threatening ventricular arrhythmias. These arrhythmias occasionally arise from epicardial. Positron emission tomogramphy-comututed tomography (PET-CT) is useful for diagnosis with sarcoidosis. However, the usefulness for prediction of ventricular arrhythmias in patients with cardiac sarcoidosis is unknown.

Objective

We hypothesized that the evaluation of pericardial fat inflammation could identify high-risk sarcoidosis patients for ventricular arrhythmias.

Methods

We enrolled 20 consecutive patients with cardiac sarcoidosis performed PET-CT between August 2016 and December 2018. In each case, we measured the maximum standardized uptake value (SUVmax) of pericardial fat around the left atrium, both ventricules, atrioventricular groove, and left main coronary.

Results

Seven patients experienced ventricular tachycardia (VT) or ventricular fibrillation (VF). VT/VF patients had significantly more complete right bundle branch block (P=0.035), larger left atrial dimension (P=0.021), larger left ventricular end-diastolic dimension (P=0.005), lower ejection fraction (P=0.007), and higher E/e' (P=0.004). SUVmax of pericardial fat in the roof of left atrium (LA) and left ventricular (LV) with VT/VF patients were significantly higher than non-VT/VF patients (LA: 1.63 vs 1.32, P=0.0311; LV: 1.84 vs 1.26, P=0.045). The cut-off values of SUVmax derived from the ROC curve in the roof of LA and LV are 1.47 and 1.59 respectively. The Kaplan Meire estimator showed that high SUVmax patients in the roof of LA had significantly more detection of NSVT.

Conclusions

Our results suggest the relationship between SUVmax and VT/VF occurrence in patients with cardiac sarcoidosis. The evaluateon of SUVmax may be useful for VT/VF risk stratification.
4092Magnetic resonance imaging of Fabry disease cardiomyopathy in patients receiving oral chaperone therapy
Authors: Muentze J , Gensler D , Cairns T , Maniuc O , Oder D , Wanner C , Frantz S , Nordbeck P
Published: October 2019

Background

Fabry disease is a lysosomal storage disorder with multiple organ involvement. Renal and cardiac symptoms can lead to dialysis and myocardial hypertrophy with fibrosis, responsible for heart failure with preserved ejection fraction (HFpEF). Enzyme replacement therapy (ERT) is available for all patients with Fabry disease since 2001, requiring infusions every other week. Since May 2016, the chaperone migalastat represents a novel form of specific therapy as the first oral therapy available for certain Fabry patients. Through this molecule the function of the mutated enzyme α-galactosidase A can be restored. Recent trials have shown positive cardiac effects of chaperone therapy using echocardiography; however, MRI investigations further evaluating these findings are not available yet.

Objective

To evaluate cardiac effects of migalastat therapy in patients with amenable α-galactosidase A mutations in the prospective monocentric HEAL-FABRY registry (NCT03362164).

Methods and results

Comprehensive clinical investigations including serial MRI were conducted at baseline before initiation of migalastat therapy and at least one year thereafter in all patients without contraindications such as pacemakers or ICDs. Out of 29 patients included in the study (mean age at start of therapy 52.8±14 years, total range 20–74 years), until then 12 patients with MRI data completed the 1-year follow-up. At 1 year, enzyme activity in leucocytes increased from 0.06 to 0.21 nmol/min/mg protein (p=0.001). Distinctive changes over time were observed not only in diastolic but also systolic parameters. The systolic myocardial mass index was reduced by 2.39% (p=0.10). In the AHA segment number 5, most important for classification of severe myocardial damage in Fabry patients, late gadolinium enhancement was reduced by 8.58% in all 5 patients with verified progressive fibrosis (p=0.14). One patient stopped migalastat therapy due to personal reasons. No significant side effects were observed.

Analysis of LGE (systolic phase)

Conclusion

These preliminary MRI data show positive effects of migalastat therapy in patients with Fabry disease and cardiac involvement. Compared to echocardiography, MRI has the potential to allow for comprehensive additional analyses regarding both cardiac morphology and function.
4093Beyond global longitudinal strain: early impairment of apical function after antracyclines therapy
Authors: Manganaro R , Longobardo L , Cusma' Piccione M , Bava A , Costantino R , Guarneri M C , Ferrazzo G , Vaccaro V , Laterra G , Aliibani L , Daffina' M G , Di Nunzio D , Altavilla G , Carerj S , Zito C
Published: October 2019

Purpose

To confirm GLS diagnostic sensitivity as parameter for the evaluation of LV systolic function in women with breast cancer who underwent chemotherapy including anthracyclines and to identify a pattern of decreased 2D speckle tracking regional longitudinal strain through the analysis of polar maps obtained with AFI technology.

Methods

We enrolled 60 female patients (age with 56.5±12 years) with breast cancer before the beginning of chemotherapy. The study protocol included clinical examination, ECG with QTc calculation, lab test (BNP and troponin I) and echocardiography with TDI and speckle tracking analysis (STI), that were performed before the beginning of the chemotherapy (basal) and after 3, 6 and 12 months. Echocardiography evaluation included the following parameters: LV end-diastolic and end-systolic volumes, LV ejection fraction (EF), average TDI S' at the mitral annulus, Global Longitudinal Strain (GLS), regional longitudinal strain, E/A ratio, E/E' ratio and sPAP. For each patient we analyzed the bull's eye maps before the beginning of the therapy (basal value) and when GLS showed the lowest values during the FU (FU value), to identify the pattern of regional longitudinal strain alterations. We compared basal and FU strain values for each of the 17 LV segments and the difference between them (delta) was calculated according to the formula [(FU LS –basal LS, (%)].

Results

During the FU, systolic blood pressure, systolic pulse pressure and BNP values increased from the basal assessment to the 3 and 6 months FU. Similarly, a progressive worsening of GLS values has been observed (basal −20.4±2.6%, 3 months FU −18.2±2.5%, 6 months FU −17.7±2.9, 12 months FU −17.6±3, p value <0.001). Through the analysis of polar maps, we observed that regional strain values worsened significantly in all the LV segments but the most evident impairment was reported in the apical cap (−22.8±3.9 vs −17.1±3.8; p<0.001, Δ=−5,78%) and in the apical segment of the anterior interventricular septum (−23.4±4.5 vs −17±6.3; p<0.001, Δ=−6,2%), as reported in Figure.

Conclusion

GLS is able to identify LV systolic dysfunction that EF is not able to detect. However, since that it describes the global function of LV, GLS could result as normal (18–20%) when strain impairment of some LV segments is counterbalanced by the compensatory strain increase of other segments, determining an misdiagnosis of myocardial damage. Regional strain and particularly the Δ-strain, seem to suggest that anthracyclines induce a damage more evident in the apical cap and in the apical segment of the interventricular septum and this pattern could be typical in these patients. Thus, polar maps analysis could be provide additional information about cardiac damage in this population.
4120Anti-tumor activity of a nanoliposomal anti-PCSK9 vaccine in BALB/c mice bearing 4T1 breast cancer
Authors: Momtazi-Borojeni A A , Nik M E , Jaafari M R , Banach M , Sahebkar A
Published: October 2019

Background

Although suppression of proprotein convertase subtilisin/kexin 9 (PCSK9) has been known to be an effective lipid-lowering approach, the efficacy and safety of PCSK9 inhibitors in non-cardiovascular diseases, particularly cancer, are yet unknown.

Purpose

The present study aimed to evaluate effect of PCSK9 inhibition on cancer behavior and endpoints in mice model of breast tumor, using a nanoliposomal anti-PCSK9 vaccine.

Methods

The nanoliposomal anti-PCSK9 vaccine was formulated via conjugation of immunogenic PCSK9 peptide to the surface of nanoliposome particles by using DSPE-PEG-Maleimide lipid. The prepared vaccine was adsorbed to Alum adjuvant (L-IFPTA+) and immunized subcutaneously four times with a bi-weekly interval in BALB/c mice.Two weeks after the last immunization, the vaccinated and unvaccinated mice were subcutaneously inoculated with 4T1 breast carcinoma cells into the right flank. After tumor mass was palpable, the mice were randomly divided into four groups and subjected to different treatment protocols: (1) PBS (untreated control), (2) vaccine group, (3) the combination group which involved vaccinated tumor-bearing mice who received single tail vein injection of Doxil®, and (4) Doxil® (positive control) group which involved unvaccinated tumor-bearing mice who received Doxil®. To evaluate therapeutic efficacy, mouse body weight, tumor size, and survival were monitored every other day for 60 days.

Results

The vaccine was found to efficiently generate specific antibodies against PCSK9 in BALB/c mice, and thereby reduce concentration of plasma PCSK9 and impede its function. Evaluation of tumor size demonstrated that time to reach endpoint (TTE) of the vaccine, combination, Doxil, and control groups was 47±10, 57±4, 60±4, 39±9 days, respectively. Rate of tumor growth in vaccine, combination, and Doxil groups was decreased by 21, 48, 53%, respectively, when compared with the control group (Figure). In the vaccine group life span was increased by 4.2%, while the survival in the combination and Doxil group was significantly lower than the control group.

Figure 1. Anti-PCSK9 vaccine efficacy.

Conclusions

Our results reveal that PCSK9 inhibition not only exerts no harmful effects, but also can moderately improve breast cancer behavior in animal model.
4181Prognosis of patients with mid-range left ventricular ejection fraction treated with PCI: insight from the global leaders study
Authors: Chichareon P , Modolo R , Kogame N , Tomaniak M , Teiger E , Quintella E F , Almeida M , Hamm C , Steg G , Juni P , Vranckx P , Valgimigli M , Windecker S , Onuma Y , Serruys P W
Published: October 2019

Background

Heart failure with mid-range ejection fraction (left ventricular ejection fraction between 40 to 49%) was introduced in the 2016 European Society of Cardiology guidelines for heart failure. The prognosis of the mid-range of left ventricular ejection fraction (LVEF) was less well assessed in patients treated with percutaneous coronary intervention (PCI).

Purpose

We aimed to assess the 2-year outcomes of patients with mid-range ejection fraction (LVEF between 40 to 49%) after PCI compared with reduced LVEF (<40%) and preserved LVEF (≥50) in the GLOBAL LEADERS study.

Methods

The GLOBAL LEADERS study was a multicenter, randomized trial comparing the efficacy and safety of two antiplatelet strategies in all-comers patients undergoing PCI with biolimus-A9 eluting stent.

Patients with available information of LVEF were eligible in the present analysis. Patients were classified according to their LVEF into three groups; preserved (LVEF ≥50), mid-range (LVEF 40–49%) and reduced (LVEF <40%) left ventricular ejection fraction. Clinical outcomes at 2 years after PCI were compared among three groups in the multivariable Cox regression analysis.

The primary outcome of present study was all-cause mortality at 2 years after PCI. The secondary outcomes were patient-oriented composite endpoint (POCE). Individual components of the composite endpoint, definite or probable stent thrombosis and bleeding academic research consortium (BARC) type 3 or 5 were also reported.

Results

Out of 15968 patients included in the GLOBAL LEADERS study, information of LVEF was available in 15008 patients (93.99%); 12,128 patients (80.81%) were in the group of preserved LVEF, 1,737 patients (11.57%) were in the mid-range LVEF group and 1,143 patients (7.62%) were in the reduced LVEF group.

The risk of all-cause mortality and POCE at 2 years were significantly different among the three groups. In an adjusted model, compared with the group of preserved LVEF, the hazard ratio for the all-cause mortality at 2 years rose from 1.89 (95% CI, 1.46–2.45) to 3.72 (95% CI, 2.95–4.70) in the group of mid-range and reduced LVEF respectively. Similar rises were observed for the POCE at 2 years from 1.27 (95% CI, 1.11–1.44) in the group of mid-range LVEF to 1.63 (95% CI, 1.42–1.87) in the group of reduced LVEF.

The risk of stroke, myocardial infarction, and definite or probable stent thrombosis in patients with mid-range LVEF was not different from patients with reduced LVEF (see figure). A similar risk of revascularization was observed among the three groups.

Outcomes among three LVEF categories

Conclusion

Patients with mid-range LVEF undergoing PCI had a different prognosis from patients with reduced LVEF and preserved LVEF in term of survival and composite ischemic endpoints at 2 years.
4223Income level and the prevalence of ischemic coronary heart disease in a low-mid-income country with high social inequalities. Influence of neighborhood walkability
Authors: Cerci R J , Baena C P , Vitola J V , Cerci J J , Pereira Neto C C , Masukawa M , Gracia A P W , Silvello L L , Prado P , Hino A A F , Fernades Silva M M
Published: October 2019

Background

The greater burden of coronary heart disease (CHD) comes from low-middle income countries (LMIC). Socioeconomic status, environmental factors, poor access to healthcare, physical inactivity and excess consumption of carbohydrates, have explained part of this burden. However, the association between income level and CHD in LMIC with marked social inequalities is not fully understood, and whether there is influence of neighborhood walkability (walking-promoting potential of the residential built environment for daily activities) in this association requires further investigation.

Purpose

To investigate to what level income is associated with ischemic CHD in a LMIC with great social inequalities and to explore the potential role of neighborhood walkability in this association.

Methods

We evaluated patients referred for myocardial perfusion imaging with SPECT (SPECT-MPI) from February 2010 to August 2017 at a reference imaging center in our city, Brazil. Each patient was georeferenced and the exposure variable was the average income in Brazilian currency (Real) per month, from the patient's residential census block. Ischemic CHD was defined by an abnormal myocardial perfusion (summed stress score >3) during a SPECT-MPI study. Walkability was measured by a score combining street connectivity, residential density, commercial density and mixed land use. We used mixed effects models to evaluate the association between income level and ischemic CHD, adjusted for potential confounders, and performed a mediation analysis to measure the percentage of this association mediated by walkability.

Results

From 26,810 participants, those living in the lowest tertile income neighborhoods were younger (61±12 vs 63±13 vs 65±12 yrs old); with higher body mass index (28.4±5 vs 27.7±5 vs 27.4±4 kg/m2); more likely to be women (52 vs 49 vs 47%), current smokers (10 vs 9 vs 8%), sedentary (79 vs 76 vs 73%), having diabetes (27 vs 24 vs 23%), hypertension (65 vs 62 vs 60%) and with known CHD (21 vs 20 vs 19%) when compared to the second and the highest tertiles respectively, all with p<0.001. After adjusting for these potential confounders, income level was inversely associated with ischemic CAD (Figure). Neighborhoods with higher income levels were associated with better walkability scores (R = 0.34eta; p<0.001), but walkability did not mediate the association between income level and ischemic CHD (percent mediated = −0.3%).

Figure 1. Association of income and CHD

Conclusions

In this large registry from a LMIC population, living in a lower-income neighborhood was associated with higher prevalence of ischemic CHD. Even though neighborhood walkability was directly associated with neighborhood income, it did not explain the association between income level and ischemic CHD.
4258Re-evaluating the genetic contribution of monogenic dilated cardiomyopathy
Authors: Mazzarotto F , Tayal U , Buchan R , Midwinter W , Wilk A , Whiffin N , Watkins H , Funke B , O'regan D , Olivotto I , Barton P J , Prasad S K , Cook S A , Ware J S , Walsh R
Published: October 2019

Background

Dilated cardiomyopathy (DCM) is genetically heterogeneous, with >100 purported disease genes tested in clinical laboratories. However, many genes were originally identified based on candidate-gene studies that did not adequately account for background population variation. Here we define the frequency of rare variation in 2538 DCM patients across protein-coding regions of 56 commonly tested genes and compare this to both 912 confirmed healthy controls and a reference population of 60,706 individuals.

Purpose

To identify clinically interpretable genes robustly associated with dominant monogenic DCM.

Methods

We used the TruSight Cardio sequencing panel to evaluate the burden of rare variants in 56 putative DCM genes in 1040 DCM patients and 912 healthy volunteers processed with identical sequencing and bioinformatics pipelines. We further aggregated data from 1498 DCM patients sequenced in diagnostic laboratories and the ExAC database for replication and meta-analysis.

Results

Specific variant classes in TTN, DSP, MYH7 and LMNA were associated with DCM in all comparisons. Variants in BAG3, TNNT2, TPM1, NEXN and VCL were significantly enriched specific patient subsets, with the last 3 genes likely contributing primarily to early-onset forms of DCM. Overall, rare variants in these 9 genes potentially explained 19–26% of cases. Whilst the absence of a significant excess in other genes cannot preclude a role in disease, such genes have limited diagnostic value since novel variants will be uninterpretable and therefore non-actionable, and their diagnostic yield is minimal.

Conclusion

In the largest sequenced DCM cohort yet described, we observe robust disease association only with a limited number of genes, highlighting their importance in DCM and translating into high interpretability in diagnostic testing. The other genes evaluated have limited value in diagnostic testing in DCM. This data will contribute to community gene curation efforts, and will reduce erroneous and inconclusive findings in diagnostic testing.

Acknowledgement/Funding

Wellcome Trust (107469/Z/15/Z), BHF (SP/10/10/28431), MRC (MR/M003191/1), Fondation Leducq (11-CVD01), Italian Ministry of Health (RF-2013-02356787)
4306Hemodynamic correlates of tricuspid annular pulmonary systolic excursion (TAPSE)/systolic pulmonary arterial pressure (SPAP) ratio in heart failure with reduced ejection fraction
Authors: Bandera F , Ghizzardi G , Agnifili M , Pizzocri S , Boveri S , Alfonzetti E , Saviano M , Giammarresi A , Bedogni F , Guazzi M
Published: October 2019

Background

The TAPSE/SPAP ratio has gained a role as an easy-to-use surrogate of right ventricle-to-pulmonary circulation (RV-PC) coupling, showing a strong prognostic significance in heart failure (HF) patients. The hemodynamic determinants of TAPSE/SPAP ratio, as assessed by invasive approach, have not been fully elucidated.

Aim

To identify the right heart hemodynamic variables correlated with TAPSE/SPAP in a HF with reduced EF (HFrEF) cohort, at rest and during exercise.

Methods

24 HFrEF patients (age 67±11 years LV EF 27±7) underwent to rest and exercise echocardiography and performed right heart catheterization within 24 hours. Bivariate correlations between TAPSE/SPAP ratio (at rest and exercise), right heart hemodynamic variables, RV systolic function and NTproBNP have been explored.

Results

TAPSE/SPAP ratio at rest showed a moderate correlation with pulmonary artery wedge pressure (PAWP: r=0.432; p=0.039), pulmonary artery pressures (PAP systolic: r=0.474; p=0.026; PAP diastolic: r=0.434; p=0.043; mPAP: r=0.476; p=0.025), pulmonary vascular resistance and compliance (r=0.475; p=0.041), while a stronger correlation was identified with right atrial (RAP systolic: r=0.571; p=0.017; RAP diastolic: r=0.675; p=0.006) and right ventricular pressures- in particular diastolic ones (RVP systolic: r=0.584; p=0.004; RAP diastolic: r=0.646; p=0.002). No significant correlation was found with NTproBNP and RV 3D EF. Exercise TAPSE/SPAP ratio significantly correlated with right atrium (RAP systolic: r=0.564; p=0.036) and right ventricle systolic pressures only (RVP systolic: r=0.765; p<0.001).

TAPSE/PAPS correlation graphics

Conclusions

TAPSE/SPAP ratio at rest showed a stronger correlation with invasively derived diastolic right heart pressure rather than pulmonary vascular bed pressures. A similar correlation was also observed for exercise TAPSE/SPAP ratio. This tight correlation with RV, rather than vascular pressures, supports the significance of the ratio as a marker of RV adaptation to vascular overload.
P3097Atrioventricular mechanical coupling and major adverse cardiac events in female patients following acute ST elevation myocardial infarction
Authors: Backhaus S J , Kowallick J T , Stiermaier T , Lange T , Koschalka A , Navarra J L , Lotz J , Kutty S , Bigalke B , Gutberlet M , Hasenfuss G , Thiele H , Eitel I , Schuster A
Published: October 2019

Background

Data on sex-specific outcomes following myocardial infarction (MI) are inconclusive with some evidence suggesting association of female sex and increased major adverse clinical events (MACE). Since underlying mechanisms remain elusive, we aimed to quantify the underlying phenotype using cardiovascular magnetic resonance (CMR) quantitative deformation imaging and tissue characterisation.

Methods

Amongst 8 centres across Germany, 795 ST-elevation MI (STEMI) patients underwent post-interventional CMR imaging. CMR feature-tracking (FT) was performed in a blinded core-laboratory. Left ventricular function was quantified using ejection fraction (LVEF) and global longitudinal/circumferential/radial strains (GLS/GCS/GRS). Left atrial function was assessed by reservoir (εs), conduit (εe) and booster pump function (εa). Tissue characterisation included infarct size (IS), microvascular obstruction (MO), area at risk and myocardial salvage index (MSI). Primary endpoint was the occurrence of major adverse clinical events (MACE) within 1 year.

Results

Female sex was associated with increased MACE (HR 1.96, 95% CI 1.13–3.42, p=0.017) but not independently of baseline confounders (p=0.526) with women being older, more often diabetic and hypertensive (p<0.001) and of higher Killip-class (p=0.010). Tissue characterisation was similar between sexes. Women showed impaired atrial (εs p=0.011, εe p<0.001) but increased systolic ventricular mechanics (GLS p=0.001, LVEF p=0.048). Ventricular strain was associated with MACE irrespective of all univariate significant baseline characteristics (GLS HR 1.08, 95% CI 1.01–1.16, p=0.036 and GCS HR 1.07, 95% CI 1.00–1.14, p=0.040).

Conclusion

Atrial function is reduced in women following STEMI, while ventricular systolic function is increased. This may reflect ventricular diastolic failure with systolic compensation, which is independently associated with MACE and may add to sex-specific prognosis evaluation.

Acknowledgement/Funding

DZHK - German Centre for Cardiovascular Research
P3106Atrial fibrillation is not associated with the responses to exercise training in heart failure patients with preserved ejection fraction
Authors: Hamazaki N , Masuda T , Kamiya K , Matsuzawa R , Nozaki K , Ichikawa T , Tabata M , Maekawa E , Fukaya H , Yamaoka-Tojo M , Matsunaga A , Ako J
Published: October 2019

Background

Atrial fibrillation (AF) is known as a common arrhythmia in heart failure patients with preserved left ventricular ejection fraction (HFpEF). Several studies have reported that HFpEF patients with AF show lower exercise tolerance and poorer prognosis as compared with those with sinus rhythm (SR). On the other hand, exercise training is documented to improve peripheral muscle function and exercise tolerance in HFpEF patients. However, the relationship between AF status and outcomes due to exercise training is still unclear in these patients.

Purpose

We aimed to investigate the influence of AF on the responses to outcomes with exercise training in HFpEF patients.

Methods

We studied 426 patients with HFpEF who received 5-month cardiac rehabilitation including exercise training during hospitalization and after hospital discharge. As clinical characteristics, we obtained body mass index, disease aetiology, comorbidity conditions, blood examination and echocardiographic variables from medical records. We also measured isometric quadriceps strength (QS) and 6-minute walk distance (6MWD) as peripheral muscle strength and exercise tolerance, respectively. The QS and 6MWD were assessed at hospital discharge as the baseline and 5 months later. AF status was determined by the presence on electrocardiogram at baseline 6MWD or medical history of AF during hospitalization. In statistical analysis, we compared baseline clinical characteristics, QS and 6MWD between the rhythm status (SR group or AF group). We also examined the changes in QS and 6MWD from baseline to the 5-month observation period (ΔQS and Δ6MWD) and compared them between the 2 groups using analysis of covariance with adjustment for baseline clinical confounding factors.

Results

At baseline, 289 patients (68%) were in SR, and 111 patients (26%) had AF. The AF was associated significantly with older age (P<0.001) and lower levels of estimated glomerular filtration rate (P=0.013), QS (P<0.001) and 6MWD (P<0.001) at baseline. The QS increased significantly from 25.2±11.0 kg at baseline to 30.8±13.0 kg after 5-month cardiac rehabilitation in the SR group, and from 21.1±8.3 kg to 26.0±9.4 kg in the AF group (P<0.001, respectively). The 6MWD also increased significantly from 394.8±129.2 to 463.5±133.5 meters in the SR, and from 343.7±107.9 to 403.0±114.5 meters in the AF (P<0.001, respectively). There were no significant differences in ΔQS and Δ6MWD between the SR and AF groups even after adjustment for clinical confounding factors including baseline QS or 6MWD (Figure).

Conclusions

The AF status in HFpEF patients was associated with older age, lower peripheral muscle function and also lower exercise tolerance at baseline, but not associated with the responses to exercise training.

Acknowledgement/Funding

JSPS KAKENHI JP16K16442
P3109Coronary vulnerable plaque development is promoted by multidirectional wall shear stress
Authors: Hoogendoorn A , Kok A M , Hartman E M J , Chiastra C , Casadonte L , Coenen A , Korteland S , Van Der Heiden K , Gijsen F , Duncker D J , Van Der Steen A F W , Wentzel J
Published: October 2019

Aim

Wall shear stress (WSS) has been widely associated with plaque development and destabilization. However, the multidirectionality of WSS, induced by the pulsatile nature of blood flow in combination with the arterial geometry, is rarely taken into account. The purpose of this study was to investigate the influence and predictive value of five (multidirectional) WSS parameters for coronary plaque progression and composition.

Methods

Familial hypercholesterolemic pigs (n=10, castrated male, 3 years old) were put on a high-fat diet and underwent imaging (near infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), optical coherence tomography (OCT) and CT) of the three main coronary arteries at baseline and 10/12 months follow-up. IVUS-based lumen contours were combined with the centerline of artery as extracted from CT to obtain a 3D reconstruction of the coronary artery. Local flow velocity measurements were combined with the 3D-geometry of the coronary arterial lumen to calculate five multidirectional WSS parameters including: time average wall shear stress (TAWSS), oscilatory shear index (OSI), relative residence time (RRT), trans wall shear stress (TransWSS), cross flow index (CFI). For the analysis, arteries were divided into 3mm/45° sectors (n=3627). Per vessel each segment was classified as low, mid or high for each WSS metric based on the average value in the sector. Changes in wall thickness (WT) and plaque composition were assessed with NIRS-IVUS and OCT, and histology and related to the local (multidirectional) WSS.

Results

Half of the pigs developed lumen intruding, complex, lipid-rich plaques. In these pigs, coronary segments exposed to low baseline levels of TAWSS exhibited a significantly larger plaque growth per month compared to regions with either mid or high TAWSS (p<0.05, see figure). Furthermore, plaque growth correlated positively with the multidirectional WSS metrics OSI, RRT and CFI, with high multidirectionality resulting in the largest plaque growth (see figure). The positive predictive values (PPV) of the WSS metrics for plaque presence (WT>0.5mm) at follow up were 50% (low TAWSS), 48% (high OSI), 49% (high RRT), 47% (high CFI) and 43% (high transWSS). The PPVs for the presence of a fibroatheroma observed with histology were 61% (low TAWSS), 58% (high OSI), 61% (high RRT), 59% (high CFI) and 49% (high transWSS).

Plaque growth vs. multidirectional WSS

Conclusions

This study shows that both low and multidirectional WSS promote the development of large and complex coronary atherosclerotic plaques with vulnerable characteristics. The high predictive values for fibrous cap atheroma development demonstrate the potential of multidirectional WSS metrics as a predictive clinical marker for vulnerable disease.

Acknowledgement/Funding

ERC- starter grant (grant agreement 310457)
P3110Tyrosine kinase inhibitor nilotinib increases atherosclerosis burden in ApoE knock-out mice
Authors: Detriche G , Zhang Y , Esposito B , Rea D , Messas E , Mirault T , Ait Oufella H
Published: October 2019

Background

In 2001, imatinib, the 1st generation tyrosine kinase inhibitor (TKI), dramatically improved the treatment and survival of the patients with chronic myeloid leukemia (CML). However, the emergence of imatinib-resistant patients led to the development of 2nd generation TKIs. Nilotinib demonstrated increased efficacy to control CML disease over imatinib and is now recommended as first-line therapy. But arterial occlusive adverse events (AOE) occurs in patients treated with nilotinib and not with imatinib. Mechanisms leading to AOE with nilotinib is not well understood. AOE are dominated by ischemic heart disease and lower extremity arterial disease. Moreover, we demonstrated that CML patients with cardiovascular risk factors are at high risk to rapidly develop AOE with nilotinib.

Purpose

To evaluate the impact of nilotinib in a pre-clinical model of atherosclerosis.

Methods

ApoE Knock-Out mice (8-week-old) were treated with either placebo (N=10), imatinib (IMA) 200mg/kg/day (N=10) or nilotinib (NILO) 100mg/kg/day (N=10) by daily feeding and a high-fat diet for 12 weeks. Heart and aorta were harvested after sacrifice, for histology staining and immunochemistry. Splenocytes were cultured from collected spleens, and Interleukin (IL) 12p70 and IL10 measured by ELISA.

Results

Mice treated with nilotinib showed an increase of atherosclerotic plaque size at the aortic sinus level: 462.1x103 μm2 vs. 344.4x103 μm2 with imatinib or 394.9x103 μm2 with placebo (p<0.05) and at the thoracoabdominal aorta level (p<0.05). Plaques had greater infiltration of macrophages: 33.0±3.4% with nilotinib vs. 7.3±1.3% with imatinib and 12.6±1.1% with placebo (p<0.001) and a larger necrotic nucleus 33.0±3.4% with nilotinib vs. 7.3±1.3% with imatinib or 12.6±1.1% with placebo (p<0.001). Nilotinib modulated the systemic immune response by increasing IL-12p70 and by decreasing IL-10 production by splenocytes after stimulation by LPS-IFNγ whereas IL10 increase was observed with imatinib.

Plaque size (aortic sinus)

Conclusion

Nilotinib has a pro-atherogenic effect in a pre-clinical model of atherosclerosis and increases the monocyte/macrophage pro-inflammatory response. Further experiments are required to identify pathways activated by nilotinib.