bluuebunny/crossref_metadata_2025 huggingface dataset:
P3580Impact of glucose-6-phosphate dehydrogenase deficiency on the extent and severity of coronary atherosclerosis in patients with acute coronary syndrome
Authors: Montereggi F , Sanna G D , Corda G , Ponti E , Murgia A , Talanas G , Saba P S , Parodi G
Published: October 2019

Background

Studies in animal models and humans suggested that glucose-6-phosphate dehydrogenase (G6PD) deficiency, a genetically inherited condition causing haemolytic anemia, may be considered a risk factor for cardiovascular disease. It is currently unknown whether enzymatic activity may impact the extent and severity of coronary atherosclerosis in patients with acute myocardial infarction. This hypothesis was tested in a cohort of acute coronary syndrome (ACS) patients undergoing invasive management from Northern Sardinia, where the population prevalence of G6PD deficiency is the highest in the Mediterranean area.

Methods

The study was based on a prospective single-centre registry of consecutive ACS patients undergoing coronary angiography and subsequent percutaneous revascularization between January 2017 and December 2018, in which G6PD activity has been measured quantitatively using a biochemical assay based on G6PD/6GPD ratio in erythrocytes. Subjects were defined as deficient when the ratio was <0.80. The primary endpoint of the study was the severity of coronary artery disease as assessed by the SYNTAX I score at baseline angiography.

Results

Among the 466 enrolled patients, 41 (9%) showed G6PD deficiency. Patients with G6PD deficiency were less likely to have a history of dyslipidemia (27% vs 50%; p=0.005) or diabetes (12% vs 21%; p=0.105). As expected, at admission patients with deficiency had lower hemoglobin level (12.1 vs 13.7 g/dL; p=0.005) as compared with those without. By angiography, SYNTAX score resulted as 19±9 and 16±9 (p=0.039) in patients with and without G6PD deficiency; while the number of diseased (with >50% stenosis) vessels was 1.9 vs 1.6 (p=0.089) in the 2 study groups. Left main disease was detected in 15% and 7% (p=0.06) patients, respectively. G6PD deficiency emerged as an independent predictor of high SYNTAX score (OR=2.16, 95% CI 1.1–4.5; p=0.037). Angioplasty with coronary stenting of the culprit vessel was performed in all patients, while GP IIb/IIIa inhibitors were used in 30% and 14% (p=0.009) of patients with and without G6PD deficiency. Finally, in-hospital events were similar between the 2 study groups.

Conclusions

An increased extent and severity of coronary artery disease was observed in ACS patients with G6PD deficiency as compared with those without, despite the lower prevalence of “classic” cardiovascular risk factors.
P3597Occurence of type 2 myocardial infarction in patients with coronary artery disease
Authors: Jeanmichel M , Putot A , Maza M , Bichat F , Pommier T , Zeller M , Cottin Y
Published: October 2019

Background

Type 2 myocardial infarction (T2MI) is an emerging entity defined by a myocardial oxygen supply and demand mismatch, in the absence of coronary thrombosis. The prevalence of T2MI is high in patients admitted for an acute MI, but is unknown in patients with coronary artery disease (CAD).

Purpose

We aimed to address the comparative prevalence and characteristics of T2 and Type 1 MI in CAD patients.

Patients

We conducted a single-center retrospective study among 33 669 consecutive patients admitted from January 2014 to December 2016 in a university hospital emergency or intensive care unit (ICU). Patients admitted for acute MI, diagnosed by troponin elevation associated with symptoms or signs of myocardial ischemia (typical chest pain and/or ECG changes) and with history of CAD were included. They were systematically adjudicated as T1MI or T2MI according to 4th MI universal definition.

Result

Among the 619 patients included, 254 (41%) had T2MI and 365 (59%) had T1MI. T2MI patients were characterized by an older age (median age [IQR]: 82 [71–87] vs 72 [62–81] y, respectively, p<0.001) and more frequent comorbidities than T1MI patients. In contrast, T2MI patients had similar rates of cardioprotective chronic treatments than T1MI. Only 41% of T2MI patients admitted in ICU underwent a coronary angiography, of whom most (56%) had three-vessels disease. Percutaneous coronary intervention was much less performed in T2MI than in T1MI (28% vs 67%, respectively p<0.001). Median (IQR) time from first CAD diagnosis to index MI was similar for both groups (83 [27–151] months vs 94 [30–179] for T1MI, respectively p=0.22). In-hospital mortality were 2 fold higher in T2MI than in T1MI (15.0% vs 6.6%, respectively, p<0.001). Moreover, in the first year following CAD diagnosis, T2MI had similar rate of occurrence than T1MI (17% vs 14%, respectively p=0.389).

Conclusion

This large real-life study in CAD patients with a recurrence of MI highlights the high frequency of T2MI. Furthermore, almost 1 out of 5 patients had an acute MI, either T1 or T2MI, within the first year after CAD diagnosis. These findings may have implications for prevention and management strategies of T2MI.

Acknowledgement/Funding

University Hospital Center Dijon Bourgogne, Agence Régionale de Santé Bourgogne Franche Comté, France
P3612Validation of Charlson Comorbidity Index to predict adverse events in elderly patients with Atrial Fibrillation and Acute Coronary Syndrome: an analysis from LONGEVO-SCA Registry
Authors: Esteve Pastor M A , Marin E , Alegre O , Castillo Dominguez J C , Formiga F , Martinez-Selles M , Diez-Villanueva P , Sanchis J , Ariza-Sole A , Marin F
Published: October 2019

Background

Aging is frequently characterized by the coexistence of several comorbid conditions that increase the adverse prognosis during hospitalization. There are few scores to analyze the impact of comorbidities in prognosis. Charlson Comorbidity Index (CCI). This score evaluates the burden of comorbidity in general population but the influence within cardiac diseases is unknown.

Purpose

The aim of this study was to analyze the relationship of CCI in adverse outcomes at short-term follow-up in elderly patients with atrial fibrillation (AF) admitted after an acute coronary syndrome (ACS).

Methods

The prospective multicenter LONGEVO-SCA included unselected elderly patients hospitalized after non-STACS. In this substudy, we analyze the influence of comorbidities in elderly AF patients, comparing high quartiles of CCI (Q3-Q4: high burden of comorbidities) to low quartiles (Q1-Q2) and the predictive performance of adverse events at 6 months follow-up of CCI.

Results

We analyzed 531 patients (mean age 84.4±3.6 years; 322 (60.6%) male). 128 (24.1%) had AF diagnosis. 91 (71.1%) patients were classified into Q1-Q2 and 37 (28.9%) patients into Q3-Q4. We analyzed the association of clinical factors and adverse events and, after Cox multivariate regression analysis, CCI was independently associated with readmissions [HR 1.19, 95% CI (1.02–1.39); p=0.020) and all-cause mortality [HR 1.32, 95% CI (1.09–1.59); p=0.003]. Patients into Q3-Q4 had higher risk of mortality than patients into Q1-Q2 [HR 5.52, 95% CI (1.01–30.3); p=0.049]. Kaplan Meier analysis showed that AF patients into Q3-Q4 had significantly worse prognosis during the follow-up with high risk of all-cause mortality (p=0.034) and readmissions due to ACS (p=0.027). We observed good predictive performance of CCI for mortality (c-statistic 0.705; p<0.001) and modest predictive performance for readmissions (c-statistic 0.627; p<0.001).

Event Free Survival according Charlson

Conclusions

Patients into high quartiles of CCI had higher risk of adverse events during the follow-up. CCI was an independent predictor of all-cause mortality and readmissions in elderly patients. Indeed, this is the first time to validate CCI to predict adverse events in AF patients with ACS.
P3624Prevalence and severity of coronary artery disease linked to prognosis in psoriasis patients referred for coronary computed tomography angiography: A multicentre cohort study
Authors: Tinggaard A B , Hjuler K F , Andersen I T , Winther S , Iversen L , Boettcher M
Published: October 2019

Background

Psoriasis (Pso) is a disease characterized by systemic inflammation and is associated with an increased risk of cardiovascular disease. However, the degree of coronary artery calcification in Pso and its relation to prognosis is largely unknown.

Purpose

The aim of this study was 1) to estimate the prevalence and severity of coronary artery disease (CAD) in this patient group and 2) to asses the risk of major adverse cardiovascular events (MACE) including revascularization and all-cause mortality after initial diagnosis and treatment in a large-scale cohort of patients who underwent coronary computed tomography angiography (CCTA) due to angina symptoms.

Methods

This study consists of two parts using data from the Western Denmark Heart Registry; a cross-sectional study included 40,125 patients and a follow-up study included 42,861 patients. Pso patients were identified by the National Patient Registry and verified by nationwide prescription and treatment code registers. Primary outcome in the cross-sectional study was a coronary artery calcium score (CACS) >0, with a secondary outcome defined as a CACS ≥400. In the follow-up study, the primary outcome was a combined outcome including myocardial infarction, revascularization, ischemic or unspecified stroke and all-cause mortality. Events within the first 90 days after CCTA were attributed to initial treatment and consequently excluded. All outcomes were adjusted for common cardiovascular risk factors and comorbidities.

Results

In the cross-sectional study 1,407 (3.5%) Pso patients were identified. OR was 1.31 (95% CI; 1.15–1.49) for CACS >0 and 1.33 (95% CI; 1.10–1.62) for CACS ≥400 in Pso patients compared to non-Pso patients. In the follow-up study 1,591 (3.7%) Pso patients were identified. The mean duration of follow-up after CCTA was 4.0 years (min/max 0.0/10.2). Crude HR for the combined outcome was 1.52 (95% CI; 1.24–1.87), while adjusted HR was 1.16 (95% CI; 0.95–1.43).

Conclusion

In this clinically relevant cohort of patients referred to CCTA for CAD rule out, coronary artery calcification was more frequent and more severe in Pso patients even compared to the control patients with several risk factors and angina symptoms, but without inflammatory diseases. An increased risk of the combined outcome of MACE including revascularization and all-cause mortality after initial treatment in Pso patients was found in the crude analysis. The increased risk seemed predominantly carried by an increase in traditional risk factors.
P3641Matrix Metalloproteinase-2 polymorphisms are associated with prognosis of patients with symptomatic coronary artery disease
Authors: Groga-Bada P , Heller F , Lente N , Hack L , Schaeffeler E , Winter S , Mueller K , Droppa M , Stimpfle F , Schwab M , Gawaz M , Geisler T , Rath D
Published: October 2019

Background

Matrix Metalloproteinase-2 (MMP-2) is involved in regulation and proliferation of vascular and endothelial cells and is therefore an important component of atherosclerotic vessels. Inhibition of MMP-2 activity is associated with improvement of cardiac function in animal models after myocardial infarction. MMP-2 single nucleotide polymorphisms (SNPs) might alter MMP-2 expression and therefore influence prognosis in patients with symptomatic coronary artery disease (CAD).

Methods and results

Genotyping for selected MMP-2 SNPs variants (rs2241145, rs2285053, rs2287076, rs243865, rs7201) was performed in 943 consecutive patients with symptomatic CAD. All patients were followed-up for all-cause death (ACD), myocardial infarction (MI) and ischemic stroke (IS) for 360 days. The primary combined endpoint (CE) consisted of either first occurrence of ACD, and/or MI, and/or IS. Secondary endpoints were defined as the single events of ACD or MI. Homozygous carriers of major allele (rs2241145, rs2287076) showed significantly better event-free survival than carriers of the minor allele for CE (Log rank = 0.022 and Log rank= 0.015, respectively). Furthermore, homozygous carriers of major allele (rs2241145, rs2285053, rs2287076) showed significantly better event-free survival for ACD (Log rank= 0.047, Log rank= 0.006 and Log rank= 0.023, respectively). In multivariate analysis, MMP-2 rs2241145, rs2287076 and rs2285053 were significantly and independently associated with CE and ACD.

Figure 1

Conclusions

MMP-2 rs2241145, rs2287076 and rs2285053 are associated with prognosis and might be valuable for further risk stratification in CAD patients.

Acknowledgement/Funding

DFG, KFO 274, CRC TR 240
P3642Predictive value of soluble urokinase-type plasminogen activator receptor for cardiovascular death and non-fatal myocardial infarction in patients with coronary artery disease
Authors: Nikorowitsch J , Borchardt T , Appelbaum S , Ojeda F , Lackner K J , Schnabel R B , Blankenberg S , Zeller T , Karakas M
Published: October 2019

Introduction

Stratification for subsequent coronary events among patients with coronary artery disease (CAD) is of considerable interest due to the potential to guide secondary preventive therapies. Soluble urokinase-type plasminogen activator receptor (suPAR) is expressed on various cells involved in atherogenesis and plaque instability, and has been associated with poor clinical outcomes in patients with various conditions.

Purpose

In this study we investigated the potential role of suPAR as a prognostic biomarker for adverse outcome in patients with CAD, and acute coronary syndrome (ACS) in particular.

Methods

Plasma levels of suPAR were measured in a cohort of 1,703 patients (AtheroGene Study) with documented coronary artery disease –including 626 patients with ACS and 1077 patients with stable angina pectoris (SAP). The main outcome measures were defined as cardiovascular death and non-fatal myocardial infarction (MI). Survival curves for the endpoints considered were computed according to thirds of the suPAR distribution. The equality of survival curves was tested using the log-rank test. Multivariable models adjusted for common cardiovascular risk factors and the biomarkers CRP, NT-proBNP and high-sensitivity troponin I (hs-TnI) in particular were also computed.

Results

The prognostic utility of suPAR was evidenced by survival curves stratified for tertiles of circulating suPAR levels –both, in the overall cohort (p=0.00062), and in the ACS cohort (p=0.00099) with a median follow-up of 3,5 years. In multivariable-adjusted Cox regression analyses the hazard ratio (HR) for the prediction of cardiovascular death was 3.60 for log-transformed suPAR levels (p<0.001) in the overall CAD cohort, whereas it was 3.34 (p=0.003) in the ACS cohort. The HR regarding prediction of the combined outcome cardiovascular death and/or non-fatal MI during follow-up was 2.19 (p<0.001) in the overall cohort, and 2.56 (p<0.001) in the ACS cohort. After multivariate adjustment, including conventional cardiovascular risk factors and hs-TnI, suPAR, after log transformation, still enabled a reliable and strong prediction of future cardiovascular death with a HR of 3.17 (p<0.001) in the overall CAD cohort, and a HR of 2.85 (p=0.014) in the ACS cohort.

Conclusions

Our study demonstrates that suPAR has a strong prognostic value independent of hs-TnI in secondary prevention settings, and thereby might represent a valuable biomarker for risk estimation in CAD.

Acknowledgement/Funding

Stiftung Rheinland-Pfalz für Innovation, European Union 7th Framework Programme, DZHK e.V., ERA-Net, Abbott Diagnostics
P3668In non-critically ill patients suffering from endocarditis partial oral antibiotic therapy is non-inferior to intravenous therapy
Authors: Wernly B , Rezar R , Lichtenauer M , Navarese E P , Alushi B , Hoppe U C , Jung C , Lauten A
Published: October 2019

Introduction

Antibiotic treatment for infective endocarditis is paramount typically consisting of intravenous therapy for up to eight weeks leading to long hospital stays. This often is associated with reduced quality of life for patients and might heighten complication rates. Recently, several trials evaluating the efficacy of partial oral treatment (switching to an oral antibiotic after an initial intravenous therapy for stabilization) versus an intravenous therapy were published. We here meta-analyze all available data.

Methods and results

Overall after screening 1848 studies at title and abstract level four studies including a total of 788 patients were included. Heterogeneity was assessed using the I2 statistic. Primary endpoint was all-cause mortality, secondary endpoint endocarditis relapse. Pooled event rates were obtained for each subset of studies and combined in a fixed-effect meta-analysis, and odds ratios were calculated using a fixed-effects model (Mantel-Haenszel).

A total of 765 patients suffered from primary left-sided endocarditis. From right-sided endocarditis suffered 72 patients. All treatment regimes were adjusted to susceptibility testing. Included patients were evaluated clinically and non-critically ill.

Rate of mortality was lower in partial oral versus intravenous strategy (OR 0.34 95% CI 0.17–0.68; p=0.003; I2 30%): In partial oral group, 11 of 379 patients died, whereas in the intravenous group, 33 of 409 patients died. Endocarditis relapse rates were not dissimilar between intravenous versus oral group (OR 0.55 95% CI 0.26–1.20; p=0.13; I2 0%) with, 10 of 459 patients in the partial oral group and 18 of 456 patients in the intravenous group evidencing a relapse.

Conclusion

Partial oral therapy is non-inferior to intravenous therapy with regards to endocarditis relapse in non-critically-ill patients suffering from both left- and right-sided endocarditis. In this meta-analysis, partial oral therapy was associated with lower mortality rates. This finding certainly needs validation in further future randomized trials comparing partial oral versus intravenous antibiotic treatment in non-critically-ill patients. As partial oral therapy allows shorter hospitalization it might be preferable and improve both quality of care and patients quality of life.
P3671Selexipag dosing and titration in the first 500 patients enrolled in SPHERE (SelexiPag: tHe UsErs dRug rEgistry)
Authors: McLaughlin V , Kim N H , Hemnes A R , Highland K B , Chin K M , Farber H W , Zhao C , Narayan V , Shah M , Chakinala M M
Published: October 2019

Introduction

SPHERE is an ongoing US-based, multicentre, prospective, registry collecting data on use of the oral selective IP prostacyclin receptor agonist selexipag in real-world settings. Here, we report selexipag dosing and titration in the first 500 patients.

Methods

SPHERE, initiated in November 2016, will enrol 800 patients newly initiated on or already treated with selexipag at enrolment who have a documented titration regimen. Patients are followed for up to 18 months. Patients were considered “newly initiated” on selexipag if they were enrolled in SPHERE ≤60 days after starting selexipag and were considered “previously initiated” if they enrolled >60 days after starting selexipag. The highest dose is the maximum dose reached during up-titration within 6 months since initiation. Selexipag “maintenance dose” is defined as the first dose received for ≥14 days without interruption or change; “titration speed” is defined as the highest dose reached within the first 6 months after initiation divided by the time (in weeks) to reach it.

Results

The data cut-off for this analysis was December 20, 2018. Most patients had Group 1 pulmonary hypertension (PH) (95.4%), which was primarily idiopathic (49.6%) or connective tissue disease associated (26.0%). At selexipag initiation 49.8% of patients had functional class III symptoms. At the time of selexipag initiation, 19.2% of patients were on PH therapy containing a prostacyclin pathway agent (PPA) (8.5% with a parenteral PPA). The median maintenance dose of selexipag was 1200 μg BID (IQR: 800–1600 μg BID) and the median time to reach it was 8.1 wks (IQR: 5.3–11.0 wks). Low (≤400 μg BID), medium (600–1000 μg BID), and high (≥1200 μg BID) maintenance doses were attained by 15.1%, 30.8%, and 49.5% of patients, respectively (and in 23.2%, 31.2%, and 36.2%, respectively, in GRIPHON). The median titration speed was 175 μg BID/wk (IQR: 110.5–195.3 μg BID/wk), slower than the protocol-outlined 200 μg BID/wk in GRIPHON. In SPHERE, most patients titrated at speeds <200 μg BID/wk, regardless of whether they were newly (175 μg BID/wk; IQR 118.6, 195.3) or previously (175 μg BID/wk; IQR 109.8, 195.3) initiated. As expected, more patients discontinued due to adverse events in the newly (29.0%) versus previously (14.1%) initiated groups. The most common adverse events leading to selexipag discontinuation were worsening pulmonary hypertension (2.2%), headache (2.0%), myalgia (1.4%), and nausea (1.0%).

Conclusion

The median maintenance selexipag dose in SPHERE was 1200 μg BID. While the median titration speed was 175 μg BID/wk, there was marked variation and the vast majority of patients titrated slower than 200 μg BID/wk. No new safety signals were observed.

Acknowledgement/Funding

Actelion Pharmaceuticals US, Inc.
P3727Left atrial appendage closure in patients with a reduced left ventricular ejection fraction: results from the prospective multicenter German LAARGE registry
Authors: Fastner C , Brachmann J , Lewalter T , Zeymer U , Sievert H , Borggrefe M , Weiss C , Geist V , Krapivsky A , Kaeunicke M , Mudra H , Hochadel M , Schneider S , Senges J , Akin I
Published: October 2019

Background and purpose

Atrial fibrillation (AF) patients with increased thromboembolic risk and contraindications for standard oral anticoagulation (OAC) can profit from an interventional left atrial appendage closure (LAAC). While impaired left ventricular ejection fraction (LVEF) is associated with an increased thromboembolic risk in AF patients, cardiac interventions are often associated with an increase in complications in this patient population, and, therefore, the LAAC procedure's success and benefit has yet to be investigated in this subgroup.

Methods

This prospective, observational LAAC registry included 622 patients with documented LVEF from 37 German centers between April 2014 and January 2016. Patients were categorized into one of three groups: LVEF >55% (preserved; p), LVEF 35–55% (mid-range; mr) and LVEF <35% (reduced; r). Procedure was conducted in a standard fashion, and baseline characteristics, imaging as well as procedural data, intra-hospital and one-year follow-up outcome were registered for each group.

Results

55.3% of patients had a pLVEF, 38.7% a mrLVEF and 5.9% a rLVEF. Patients with rLVEF were more often affected by coronary artery disease (p<0.001 for trend), and had an elevated CHA2DS2-VASc (4.3±1.5 vs. 4.8±1.5 vs. 5.3±1.6; p<0.001) and HAS-BLED score (3.7±1.1 vs. 4.1±1.2 vs. 4.3±0.9; p<0.001). Percentage of prior cerebrovascular events and major bleedings was comparable at baseline (each p=n.s.). Procedural success was high (97.9%), while rates of intra-hospital MACCE (0.5%) and other major complications (4.2%) were low, with no significant difference between the groups (each p=n.s.). MACCE during follow-up was more frequent in rLVEF patients (11.0 vs. 11.3 vs. 27.8%; p=0.013), which was mainly driven by myocardial infarctions and all-cause deaths in this high risk collective. Likewise, Kaplan-Meier estimation showed a lower overall survival in this group (89.7 vs. 89.3 vs. 74.6%; p<0.01). On the contrary, rates of stroke were extremely low across all groups and statistically similar (0.3 vs. 1.0 vs. 0%; p=n.s.). This was 93.4, 82.7 and 100.0% less in comparison to the estimated risk calculated from the CHA2DS2-VASc score

Conclusions

The LVEF had no influence on the procedural success as well as the intra-hospital complications after LAAC. Annual rate of stroke was low across all groups, and risk reduction was substantial especially in this high risk collective, as compared to the estimated risk.

Acknowledgement/Funding

Stiftung Institut für Herzinfarktforschung, Ludwigshafen, Germany
P3783A higher habitual flavonoid intake is associated with a lower risk of atrial fibrillation
Authors: Bondonno N , Murray K , Bondonno C P , Lewis J R , Croft K D , Kyro C , Gislason G , Tjonneland A , Scalbert A , Cassidy A , Piccini J P , Overvad K , Dalgaard F
Published: October 2019

Background

Our understanding of how diet affects future risk of atrial fibrillation (AF) is limited. Evidence suggests that higher habitual intakes of flavonoids, bio-active compounds found in plant-based foods and beverages, lower cardiovascular disease risk, attenuate inflammation, and may have anti-arrhythmic properties.

Purpose

To investigate the association between flavonoid intake and clinically apparent AF in a large cohort of Danish men and women.

Methods

Baseline data from 55 634 participants without AF of the Danish Diet, Cancer and Health Study, recruited from 1993 to 1997, were cross-linked with Danish nationwide registries. Flavonoid intake was calculated from validated food frequency questionnaires using the Phenol-Explorer database. Associations between flavonoid intake and AF hospitalisation were examined using restricted cubic splines based on Cox proportional hazards models with adjustments for age, sex, BMI, smoking status, physical activity, alcohol intake, income, and hyperthyroidism.

Results

After a median [IQR] follow-up of 21 [18–22] years, 6 301 participants were hospitalised with AF. Non-linear associations were observed for total flavonoid intake and for all flavonoid sub-classes. For total flavonoid intake, after adjusting for potential lifestyle confounders and compared to participants in quintile 1 (median intake: 173 mg/day), those in quintile 3 (median intake: 320 mg/day) and quintile 4 (median intake: 494 mg/day) had a significantly lower risk of AF, with hazard ratios (95% CI) of 0.93 (0.87, 0.99) and 0.92 (0.86, 0.98), respectively. Compared to median intake in the lowest quintile, a total flavonoid intake of 1000 mg/day was associated with a lower risk of AF in smokers [0.86 (0.77, 0.96)] but not in non-smokers [0.96 (0.88, 1.05)], a lower risk of AF in high alcohol consumers [>20 g/d: 0.84 (0.75, 0.94)] but not in low-to-moderate alcohol consumers [<20 g/d: 0.97 (0.89, 1.06], a trending lower risk of AF in diabetics [0.76 (0.51, 1.14)] but not in non-diabetics [0.95 (0.89, 1.02)], and a trending lower risk of AF in those with ischaemic heart disease [0.84 (0.65, 1.09)] but not in those without [0.96 (0.89, 1.03), Figure 1].

Figure 1

Conclusion

We observed an inverse association between total flavonoid intake and AF, most notably in sub-populations with known lifestyle and disease risk factors for AF. This finding warrants investigation in randomised controlled trials. If confirmed, ensuring the adequate consumption of flavonoid-rich foods, particularly in individuals “at risk”, may be an important strategy to mitigate AF risk.

Acknowledgement/Funding

The Danish Diet, Cancer, and Health Study was funded by the Danish Cancer Society.
P3793Spironolactone in patients with permanent atrial fibrillation, possible heart failure protective potential
Authors: Dabrowski R , Chwyczko T , Kowalik I , Smolis-Bak E , Borowiec A , Maczynska J , Dobrowolski M , Szwed H
Published: October 2019

Background

Atrial fibrillation (AF) promotes electrical, neurohormonal and structural remodeling of atria and ventricles. Long lasting AF leads to atrial interstitial fibrosis, apoptosis, loss of myofibrils and finally to heart failure (HF).

Purpose

The aim of the study was impact of aldosterone antagonist, spironolactone, on exercise tolerance and neurohormonal activity in patients with permanent AF without symptoms of HF.

Methods

In prospective, randomized study patients with permanent AF at least for 1 year, no signs and symptoms of HF and stable clinical condition were included. Patients were randomized to: beta-blocker plus spironolactone (dose: 25 mg) treatment and rate-control treatment with only beta-blocker. Propranolol, metoprolol and bisoprolol were used, doses were adjusted to achieve resting heart rate 60–80/min. Ergospirometry (CPX) and 6-minute walk (6-MWT) tests were performed during separate days.

Results

Study group consisted of 49 patients, 69% men, mean age 62.1±9.6 without structural and chronic active diseases, mean time of arrhythmia was 5.5 years, Q1: 2, Q3: 8 years. Follow-up was 11.2 months. All patients were treated with beta-blockers, 27 patients were treated with 25 mg spironolactone. Surprisingly physical capacity in 6-minute walk test (6-MWT) in studied patients was not significantly reduced in comparison with values ranges for healthy volunteers. After 11.2 months follow-up significantly longer exercise time (433±113 vs. 367±162 sec, p<0.05) and lower maximal HR (159±25 vs. 165±22 beats/min, p<0.0550) were observed in spironolactone treated group. Other CPX variables did not differ significantly between groups after 11,2 months: VO2: 20.7±5.1 vs. 20.1±4.8 [ml/kg/min]; VO2 as % of normal value: 78.4±15.2 vs. 76.8±15.2; O2 pulse: 12±2.8 vs. 12.7±3.6 [ml/beat]; AT: 1.4±0.3, 1.6±0.5 [L/min]; VE: 74.9±20.0, 72.6±17.9 [L/min]. All spirometric variables worsened after 11.2 months: VC: 4.3±1.1 vs. 3.8±0.8 [L], p<0.0005, FVC: 4.2±1.1 vs. 3.8±1.0 p<0.005 [L], FEV1: 3.1±0.8 vs. 2.8±0.7 [L], p<0.01. In spironolactone treated group after 11.2 months BNP concentrations were significantly lower: Q1: 54, Q2: 83, Q3: 100 vs. Q1: 42, Q2: 93; Q3: 184 ng/L (p=0.025) and aldosterone levels were markedly increased: Q1: 216, Q2: 266; Q3:443 vs. Q1: 169; Q2: 228; Q3:294 ng/dL (p=0.0007).

Conclusions

In patients with permanent atrial fibrillation cardiopulmonary exercise responses were markedly abnormal, but exercise capacity was increased after spironolactone treatment. Deterioration of spirometry results might be due to beta-blocker treatment. In spironolactone treated group BNP levels were significantly lower what may correspond to its heart failure protective activity.
P3804Left ventricular wall thickness measured with computed tomography predicts mitral regurgitation improvement in patients implanted with cardiac resynchronization therapy
Authors: Galand V , Ghoshhajra B , Szymonifka J , Das S , Orencole M , Leclercq C , Truong Q A , Singh J P
Published: October 2019

Background

Secondary mitral regurgitation (MR) is common in heart failure (HF) patients and results in progressive left ventricular (LV) dilatation, papillary muscle (PM) displacement and mitral valve leaflet tethering. In selected HF patients, cardiac resynchronization therapy (CRT) has been proved to reduce MR by LV reverse remodeling, resynchronization of PM insertion site contraction and reduction in MV tenting area and inter PM distance. However, data regarding the impact of LV wall thickness (WT) on MR improvement are scarce.

Methods

In this prospective study, a total 54 patients scheduled for CRT, underwent pre procedural CT. Reduced LV WT was defined as WT<6mm and was quantified as a percentage of total LV area. LV was segmented in 17 segments to assess the number of LV segments with reduced WT. End point was 6-month echocardiographic MR improvement by ≥1 class. For this analysis, we focused on patient with mild (class 2) to severe (class 4) MR.

Results

Among the 54 patients, 38 (70.4%) had mild to severe MR at baseline and a total of 16 (42.1%) experienced MR improvement by ≥1 class at 6 months. there was no difference regarding the co-morbidities, electrocardiogram and echocardiographic parameters between patients with or without MR improvement. However, patients without MR improvement had significant higher NT-pro BNP level at baseline. Interestingly, patients without MR improvement had larger LVWT <6mm area (41.541.5±19.4 vs. 22.4±16.1%, p=0.003) associated with higher number of papillary muscle (PM) inserted in reduced LV WT area. In multivariate analysis, an area ≥25% of LVWT<6mm including at least 1 PM insertion was the only predictor of no MR improvement at 6 months (HR 18.4 (1.25–271.75), p=0.034). Lastly, patients with MR improvement had significant lower rate of basal segments with reduced WT, especially in the lateral location. Of note, patients with MR improvement exhibited fewer rate of postero-lateral WT <6mm segments.

Left ventriculat segmentation

Conclusion

LV WT evaluated using CT is a strong predictor of no MR improvement in HF patients with mild to severe MR and who scheduled for CRT implantation.
P3816Cost-effectiveness of ventricular tachycardia catheter ablation: limitations in the current trial evidence base
Authors: Chen Y , Gomes M , Garcia J V , Lambiase P D
Published: October 2019

Introduction

Randomised clinical trials (RCTs) have suffered from criticisms including a lack of generalisability as well as a lack of cost-effectiveness analysis of the different interventions being studied. Such analyses are used by organisations including the UK's National institute for Health and Care Excellence (NICE) to inform system-level decisions regarding which treatments are funded. There is the potential for a growing chasm to exist between what is the latest innovation in cardiology and what can be afforded.

Purpose

To evaluate the cost-effectiveness of ventricular tachycardia (VT) catheter ablation versus anti-arrhythmic drug (AAD) therapy in ischemic heart disease.

Methods

A decision-analytic Markov model was used to calculate the costs and health outcomes of catheter ablation or AAD treatment of VT for a hypothetical cohort of patients with ischaemic cardiomyopathy andan implantable cardioverter defibrillator (ICD). Model inputs where informed using RCT-level evidence [Table 1] wherever possible. Costs were calculated from a UK perspective.

Results

Catheter ablation vs. AAD therapy had an incremental cost-effectiveness ratio (ICER) of £144,150 (€161,448) per quality adjusted life year (QALY) gained, over a five-year time horizon. The ICER for a ten-year time horizon was £75,074 (€84,083) and £69,986 (€78,384) over the cohort's lifetime. Using probabilistic sensitivity analyses to account for model parameter uncertainty, the likelihood of catheter ablation being cost-effective was only 11%, assuming a willingness to pay threshold of £30,000 used by the NICE [Figure 1].

Table 1. Summary of RCT level source data used to inform Markov model inputs Name of trial SMASH VT VTACH SMS CALYPSO VANISH VISTA Sample size 128 110 111 27 259 118 Mean age 67 66 67 64 68 66 Control AAD AAD AAD AAD AAD Clinical ablation Intervention Ablation Ablation Ablation Ablation Ablation Substrate ablation Length of follow up 22 months 24 months 28 months 6 months 28 months 12 months Mortality (%) 11% [AAD] 7% [AAD] 19% [AAD] 14% [AAD] 28% [AAD] 15% [C-ablation] vs. vs. vs. vs. vs. vs. 9% [Ablation] 10% [Ablation] 17% [Ablation] 15% [Ablation] 27% [Ablation] 9% [S-Ablation] Readmission (%) 19% [AAD] 55% [AAD] 44% [AAD] 50% [AAD] 31% [AAD] 32% [C-ablation] vs. vs. vs. vs. vs. vs. 12% [S-ablation] 6% [Ablation] 33% [Ablation] 39% [Ablation] 38% [Ablation] 25% [Ablation]

Cost-effectiveness acceptability curve

Conclusion

Catheter ablation of VT is unlikely to be cost-effective compared with AAD therapy alone in patients with ischaemic cardiomyopathy implanted with an ICD based on pooled trial evidence. However, better designed studies incorporating detailed and more frequent quality of life assessment are needed to advise health policy in this field and to provide more informed cost-effectiveness analyses.

Acknowledgement/Funding

NIHR Academic Clinical Fellowship
P3822Risk prediction for ASCVD in primary prevention patients on statin therapy
Authors: Pagidipati N , Wojdyla D M , Robinson J , Navar A M , Peterson E D , Pencina M
Published: October 2019

Background

Statins are now widely used for the primary prevention of atherosclerotic cardiovascular disease (ASCVD). However, existing risk prediction models were developed primarily on patients not on statins. We developed a novel model to estimate the risk of ASCVD among contemporary patients taking statins.

Methods

Using combined data from 3 large NIH-sponsored cohort studies: Atherosclerosis Risk in Communities, Framingham Offspring Study, and Multi-ethnic Study of Atherosclerosis we examined adults aged 40–79 years without prior ASCVD who were on statin therapy at the baseline exam. A Cox proportional hazards model was used to identify factors associated with a 10-year risk of CV death, MI, or stroke. Age, sex, and race were forced into the model while other potential candidate predictors were retained if statistically significant at the 0.05 level. Interaction terms with age, sex, and race were retained if significant at the 0.01 level. The model was assessed with c-statistic and calibration plots of observed events versus model-based risks after cross-validation and contrasted with the Pooled Cohorts Equations (PCE) recommended by the current U.S. guidelines.

Results

Among 2333 primary prevention patients on statins at baseline, a total of 220 events occurred over a median 8.8 years of follow-up. Most risk factors retained in our final model overlapped with those included in the PCE (age, sex, race, systolic blood pressure [sBP], diabetes, smoking, high-density lipoprotein cholesterol, total cholesterol). Our model also included creatinine clearance, aspirin use, and the interaction between age and sBP. Optimism-corrected discrimination of the new model was marginally higher than PCE: 0.69 (95% CI 0.66–0.72) versus 0.68 (95% CI 0.65–0.72). Cross-validated calibration was superior on our contemporary sample, especially at the higher levels of risk (Figure), where PCE over-estimated risk.

Calibration plots

Conclusion

Accurate estimation of 10-year ASCVD risk among patients currently on statins necessitates recalibration of the current PCE model or application of our algorithm developed specifically for this cohort. This might help avoid over-estimation of risk and reduce the need for unnecessary additional lipid-lowering therapy.

Acknowledgement/Funding

Regeneron Pharmaceuticals
P3848Baseline profile of patients treated for acute venous thromboembolism (VTE) in routine clinical practice according to VTE location in the RE-COVERY DVT/PE global cohort study
Authors: Schellong S , Ageno W , Casella I B , Han C K , Schulman S , Singer D E , Desch M , Tang W , Voccia I , Zint K , Goldhaber S Z
Published: October 2019

Background

In contrast to randomized clinical trials, observational studies provide the opportunity to evaluate routine practice in real-world patient populations.

Purpose

Using data from the RE-COVERY DVT/PE global observational study (enrollment January 2016 to May 2017), we have explored patient characteristics and anticoagulant treatment patterns in subgroups defined according to the type and location (proximal or distal lower limb) of acute venous thromboembolism (VTE).

Methods

Baseline patient characteristics, details of hospitalization and choice of anticoagulant therapy were tabulated descriptively for three groups of patients according to the type and location of their index VTE: pulmonary embolism (PE) (± any deep vein thrombosis; DVT); proximal (± distal) lower limb DVT, including the iliac vein; or distal lower limb DVT. Anticoagulant therapy at baseline and at hospital discharge or 14 days after diagnosis (whichever was later) was recorded.

Results

Of the 6122 eligible patients, 324 who had DVT at locations other than the lower limb and no PE were excluded from this analysis (as a key objective was to compare subgroups with DVT in the lower extremities according to whether the location was distal alone or involved the proximal segment). The remaining 5798 patients had either distal DVT (17.7%), proximal (± distal) DVT (40.0%) or PE (± any DVT) (42.3%) (Table). The likelihood of being diagnosed in an emergency department and of being hospitalized for VTE increased in line with the seriousness of the index event (distal DVT to PE). There were corresponding increases in age and the proportion of patients with comorbidities and/or medical history such as hypertension, diabetes mellitus or active cancer across these subgroups. At the time of hospital discharge or 14 days after diagnosis, whichever was later, non-vitamin K antagonist oral anticoagulants were the most commonly used anticoagulants (53% of patients in the PE group and 55–56% in the two DVT groups). The use of parenteral anticoagulant therapy alone appeared to be lower in the PE group than in the DVT groups, but the total use of parenteral therapy (alone or prior to oral anticoagulation) increased across groups from distal DVT (67%) to proximal DVT (74%) to PE (79%).

Conclusion

These data provide an insight into the potential differences in patient characteristics and treatment patterns among patients with PE, proximal/iliac lower limb DVT or distal lower limb DVT.

Acknowledgement/Funding

Funded by Boehringer Ingelheim
P3855Incidence, risk factors and impact of readmission for heart failure after successful transcatheter aortic valve replacement
Authors: Guedeney P , Huchet F , Manigold F , Rouanet S , Vicaut E , Balagny P , Leprince P , Lebreton G , Letocart V , Barthelemy O , Montalescot G , Guerin P , Collet J P
Published: October 2019

Background

Incidence and correlates of readmission for heart failure in all-comers, after successful transcatheter aortic valve replacement (TAVR) remain unclear.

Objective

We sought to evaluate the incidence, risk factors and clinical impact of readmission for HF after successful TAVR in an unselected patient population.

Methods

All patients who underwent successful TAVR in two high-volume French tertiary centers from February 2010 to December 2016 were prospectively included and followed-up for one year. Cox multivariate model was used to assess risk factors of readmission for heart failure, evaluated a time-updated covariate and mortality.

Results

A total of 1139 patients (mean age 82.4±7.7 years, 52.2% male) were included. Readmission for heart failure occurred in 99 (8.7%) patients. Risk factors of readmission for HF were chronic pulmonary disease (adjHR 1.8; 95% CI [1.2–2.8], p=0.008), chronic kidney disease (adjHR 1.7; 95% CI [1.1–2.6], p=0.01), diabetes mellitus (adjHR 1.7; 95% CI [1.1–2.5], p=0.01), prior atrial fibrillation (adjHR 1.6; 95% CI [1.1–2.4], p=0.02) and post-TAVR left ventricular ejection fraction (LVEF) ≤35% (adjHR 2.1 95% CI 1.2–3.7, p=0.009). Readmission for HF was strongly associated with mortality (Figure) along with increased STS score (adjHR 1.07 95% CI 1.03–1.12, p=0.002), prior atrial fibrillation (adjHR 2.13 95% CI 1.53–2.96, p<0.001) and shock during the index hospitalization (adjHR 2.68 95% CI 1.48–4.87, p=0.001).

Figure 1

Conclusion

Readmission for heart failure occurs in one out of ten patients after successful TAVR and is strong risk factor of mortality. Comorbidities and post-TAVR LVEF≤35% are the main correlates of readmission for heart failure.

Acknowledgement/Funding

ACTION study group
P3858High H2FPEF score is an independent predictor of adverse outcome in patients with severe aortic stenosis and preserved ejection fraction undergoing TAVR
Authors: Ludwig S , Voigtlaender L , Ruebsamen N , Kalbacher D , Koell B , Linder M , Waldschmidt L , Schirmer J , Seiffert M , Conradi L , Schaefer U , Reichenspurner H , Blankenberg S , Westermann D , Schofer N
Published: October 2019

Background

Recently, the H2FPEF score has been developed in an evidence-based approach relying on simple clinical and echocardiographic variables. It enables the identification of patients with high probability of prevalent heart failure with preserved ejection fraction (HFpEF) which is associated with a dismal prognosis. Left ventricular diastolic dysfunction, a key mechanism in HFpEF, is also a common finding in patients with severe aortic stenosis.

Objective

To assess the prognostic impact of the H2FPEF score in patients with preserved ejection fraction and severe aortic stenosis undergoing Transcatheter Aortic Valve Replacement (TAVR).

Methods

Among 1148 patients with preserved ejection fraction who received TAVR at our institution between 2013 and 2018, data for calculation of the H2FPEF score was available in 535 patients. Score variables include BMI >30 kg/m2, arterial hypertension, atrial fibrillation, pulmonary hypertension >35 mmHg, age >60 years, and elevated LV filling pressure. Patients were dichotomized according to “low” (1–5 points; n=377) and “high” H2FPEF scores (6–9; n=158). Kaplan-Meier survival curves and Cox regression analyses were used to assess the prognostic impact of H2FPEF scores. Median follow-up time was 0.3 years.

Results

TAVR patients presenting with high H2FPEF scores had higher prevalence of moderate to severe mitral regurgitation (19.4% vs. 33.6%, p<0.001) as well as tricuspid regurgitation (15.2% vs. 35.1%, p<0.001), and presented with lower stroke volume index (42.2 ml/m2 vs. 36.0 ml/m2, p<0.001) compared to those with low H2FPEF scores. All-cause mortality one year after TAVR was significantly higher in patients in the high H2FPEF score group (10.5% vs. 21.0%, p=0.0019, Figure 1). Multivariate analysis revealed a high H2FPEF score to be independently predictive for 1-year all-cause mortality (HR 2.66, 95% CI: 1.41–5.02, p=0.025). Among the single H2FPEF score variables, atrial fibrillation (HR 3.45, 95% CI: 1.86–6.40, p<0.001) and systolic pulmonary hypertension >55 mmHg (HR=2.68, 95% CI: 0.97–7.40, p=0.057) were strong independent predictors of adverse outcome.

Figure 1. All-cause mortality of patients undergoing TAVR after one year stratified by low (1–5 points) and high (6–9) H2FPEF score

Conclusion

An elevated H2FPEF score of >6 is independently predictive for mortality in patients with preserved ejection fraction undergoing TAVR for severe aortic stenosis. Our findings provide evidence that the H2FPEF score, which was meant for diagnostic use originally, is able to serve as a prognostic tool in patients with preserved ejection fraction undergoing TAVR, highlighting the adverse impact of diastolic dysfunction in patients with preserved ejection fraction and aortic stenosis.
P4154MicroRNA Signatures Predict Early Major Coronary Events in Middle Aged Men and Women
Authors: Gigante B , Papa L , Bye A , Kunderfranco P , Viviani C , De Faire U , Briguori C , Bottai M , Condorelli G
Published: October 2019

Background

The role of microRNA as biomarkers able to predict major coronary events (MACE) has not been fully elucidated, reproducibility being a critical issue.

Aim

To identify circulating microRNA signatures able to predict MACE.

Methods

We employed a PCR-based method to screen 754 microRNAs in a cohort of 60-year-olds (60YOs) from Stockholm, using a nested case-control design (100 cases vs 100 matched controls). The association of microRNAs and their interaction with the risk of MACE (myocardial infarction (MI), angina and sudden cardiac death) was estimated with random-effect logistic regression and expressed as OR with 95% CI. A bioinformatics approach identified microRNA clusters based on predicted targets. Main findings were tested in 58 MI and 60 age and sex matched referents from the the Nord-Trøndelag Health (HUNT) Study, a longitudinal population health study conducted in Norway.

Results

Fifty-five microRNAs were found to be associated with risk of MACE in the 60YO. MicroRNA-145-3p was associated with the largest estimated risk increase of MACE after adjustment for the common CV risk factors (OR: 2.18; 95% CI: 1.27–3.75). Interaction analysis revealed that increasing plasma levels of microRNA-320b modulated the association of 16 microRNAs with risk of MACE. As an example the estimated MACE risk associated with microRNA-145-3p was 1.47 (0.87–2.47) in the presence of low (<25th percentile) and 4.00 (1.79- 8.93) in the presence of high (>75th percentile) miRNA 320b expression levels. Sixteen microRNA pairs could be classified in 4 functional clusters with 492 predicted gene targets, mainly involved in the regulation of inflammation, thrombosis and lipid metabolism. Eight miRNAs interacting pairs belonging to cluster 2 and 4 showed a similar association trend with MI risk in the HUNT study.

Conclusions

We report the identification of microRNA signatures predicting risk of MACE in middle-aged Scandinavian men and women. These signatures could be a valuable tool to improve CV disease prediction in the aged.