bluuebunny/crossref_metadata_2025 huggingface dataset:
P4659Left ventricular thrombus and arterial embolism in patients with noncompaction cardiomyopathy - Prognostic value of cardiac magnetic resonance imaging
Authors: Schneider B , Huemme T H , Schwab J , Gerecke B , Desch U , Vorbringer H
Published: October 2019

Background

Left ventricular noncompaction cardiomyopathy (LVNC) is characterized by an increased number of LV trabeculations with deep intertrabecular recesses. This abnormality is associated with heart failure, arrhythmias and arterial embolic events (AE). At present, it is unknown if AE is mainly due to blood stasis within the intertrabecular recesses, reduced LV ejection fraction or concomitant atrial fibrillation. LVNC is usually diagnosed by echocardiography but cardiac magnetic resonance imaging (CMRI) has evolved as an alternative method.

This study assessed the prognostic value of CMRI for arterial embolic events in patients (pts) with LVNC.

Methods

34 consecutive pts (19m, 15f, age 53±16) with LVNC underwent cine and contrast-enhanced CMRI with a 1.5 T scanner. LV diameter, volume, ejection fraction, and ratio of noncompacted to compacted myocardium (NC/C) were determined, and in 32 pts presence and localization of late gadolinium enhancement (LGE) was assessed. Clinical and CMRI findings were compared in pts with and without LV thrombus and/or AE.

Results

Overall, 20 pts (59%) were in heart failure NYHA III or IV, 14 (41%) had left bundle branch block (LBBB), 7 (21%) paroxysmal atrial fibrillation and 6 (19%) ventricular tachycardia (VT). By CMRI, LV diameter in end-diastole (66±8 mm), end-systole (53±10 mm), end-diastolic (229±69 ml) and end-systolic volume (150±68 ml) were enlarged and ejection fraction (36±14%) was reduced. The NC/C ratio was 3.2±1.4 in end-diastole and 2.6±1.4 in end-systole. One pt had right ventricular involvement with a thrombus. LGE was seen in 9/32 pts (28%) in the compacted myocardial layer (n=6), in the noncompacted trabecular layer (n=6) and within the papillary muscles (n=3). LGE was present in 3 areas in 1 and in 2 areas in 4 pts.

In 3 pts (9%) a thrombus was seen within the trabecular layer which resolved under anticoagulation, and 6 additional pts (18%) without detectable thrombus experienced AE (transient ischemic attack n=1, stroke n=5). Thrombus and/or AE were not associated with age, sex, NYHA class, larger left atrial or LV diameter, LV volume, LBBB or documented VT. Atrial fibrillation (2/9 vs 5/25 pts, p=ns), LV ejection fraction (33±13% vs 38±15%, p=ns) and the NC/C ratio in end-diastole (median 3.2 vs 3) or end-systole (both median 2.6, p=ns) were similar. Thrombus and/or AE occurred mainly in pts with LGE (6/9 vs 2/23 pts, p=0.002).

Conclusion

In LVNC, evaluation by CMRI and demonstration of LGE in the compacted or noncompacted myocardium identifies patients at high risk for thrombus formation and/or arterial embolic events, warranting anticoagulation.
P4661Increased levels of sST2 in patients with mitral annulus disjunction and ventricular arrhythmias
Authors: Scheirlynck E , Dejgaard L , Skjolsvik E , Lie O H , Motoc A , Hopp E , Tanaka K , Ueland T , Ribe M , Collet C , Edvardsen T , Droogmans S , Cosyns B , Haugaa K
Published: October 2019

Background

Mitral annulus disjunction (MAD), a basal displacement of the mitral valve annulus, is described as a possible aetiology of sudden cardiac death. Stretch-induced fibrosis in the sub-valvular apparatus has been suggested as the substrate of arrhythmias.

Purpose

We hypothesized that the stretch related biomarker soluble Suppression of Tumorigenicity-2 (sST2) is a marker of ventricular arrhythmias in patients with MAD.

Methods

We included patients with ≥1 mm MAD on cardiac magnetic resonance imaging, and recorded left ventricular ejection fraction (LVEF) and late gadolinium enhancement (LGE) suggesting papillary muscle fibrosis. Circulating levels of sST2 were assessed by blood sampling. The occurrence of ventricular arrhythmias, defined as aborted cardiac arrest, sustained or non-sustained ventricular tachycardia, was assessed retrospectively.

Results

We included 72 patients with MAD [55 (35–62) years old, 48 (67%) female], of which 22 (31%) had ventricular arrhythmias. Patients with ventricular arrhythmias had lower LVEF (60±6% vs. 63±6%, p=0.04), more prevalent papillary muscle fibrosis [14 (64%) vs. 10 (20%), p<0.001] and higher sST2 levels [31.6±10.1 ng/mL vs. 25.3±9.2 ng/mL, p=0.01] compared to those without. Combining sST2-level, LVEF and papillary muscle fibrosis optimally detected individuals with arrhythmias (area under the curve 0.82, 95% CI 0.73–0.92) and improved the risk model (p<0.05) compared to individual parameters (Figure right panel).

Conclusion

Circulating sST2 levels were higher in patients with MAD and ventricular arrhythmias compared to patients without arrhythmias. Combining sST2, LVEF and LGE may improve risk stratification in patients with MAD.

Acknowledgement/Funding

This work was supported by public grant [203489/030] from the Norwegian Research Council, Oslo, Norway. E. Scheirlynck received an ESC research grant
P4673Macitentan in chronic thromboembolic pulmonary hypertension (CTEPH): combined data from OPUS and OrPHeUS real-world data sets
Authors: Channick R , Chin K , Kim N , McConnell J , Poch D , Flynn M , Leber L , Morganti A , McLaughlin V
Published: October 2019

Introduction

The OPsumit® USers Registry (OPUS) provides real-world data in patients (pts) with pulmonary hypertension newly started on macitentan. The OPsumit® Historical USers cohort (OrPHeUS) study was conducted to supplement OPUS to fulfil the FDA request to characterise the safety of macitentan in clinical practice. Both studies included pts with CTEPH.

Purpose

To describe the characteristics and safety outcomes of CTEPH pts newly treated with macitentan.

Methods

OPUS is a prospective, US, multicentre, long-term, observational drug registry (NCT02126943) ongoing since Apr 2014. OrPHeUS was a retrospective, US, multicentre medical chart review (NCT03197688); data collected Oct 2013-Mar 2017. This subgroup analysis describes CTEPH patient characteristics at macitentan initiation, hospitalisations, survival and liver function tests (LFTs) in the combined OPUS/OrPHeUS data set. LFTs are also provided for the OPUS/OrPHeUS pulmonary arterial hypertension (PAH) population.

Results

As of Oct 2018, OPUS/OrPHeUS included 144 CTEPH pts with follow-up data. At macitentan initiation, median (Q1, Q3) age was 66 (56, 73) years; of the 53 pts with a WHO functional class (FC) assessment, 35.8%, 49.1% and 15.1% were in FC II, III and IV, respectively. Median (Q1, Q3) time from CTEPH diagnosis was 18.6 (7.4, 56.4) months (n=141). At macitentan initiation, 32.6% of pts had no PAH therapy, 63.9% were receiving one and 3.5% were receiving two PAH therapies. Median (Q1, Q3) exposure to macitentan was 15.9 (4.3, 30.4) months. There were 43 (29.9%) CTEPH pts who discontinued treatment; 23 due to an adverse event (AE), 0 due to a hepatic AE (HAE) and 20 not due to an AE/HAE. There were 58 (40.3%) CTEPH pts who experienced ≥1 hospitalisation and 9 (6.3%) pts died. LFTs are presented in the table.

LFTs CTEPH follow-up pts PAH follow-up pts (N=144) (N=4072) ALT or AST ≥3x ULN   Pts with ≥1 event, n (%) 1 (0.7) 132 (3.2)   Incidence rate per 1 person-year (95% CI) 0.005 (0.001, 0.035) 0.024 (0.020, 0.029) ALT or AST ≥3x ULN and total bilirubin ≥2x ULN   Pts with ≥1 event, n (%) 1 (0.7) 27 (0.7)   Incidence rate per 1 person-year (95% CI) 0.005 (0.001, 0.035) 0.005 (0.003, 0.007) ALT: alanine aminotransferase; AST: aspartate aminotransferase; CI: confidence interval; ULN: upper limit of normal.

Conclusions

Analysis of OPUS/OrPHeUS data provides further insight into real-world use of macitentan in CTEPH pts. The observed hepatic safety profile in CTEPH pts is in line with that of PAH pts.

Acknowledgement/Funding

Actelion Pharmaceuticals Ltd
P4692Pronostic factors after arterial switch operation for transposition of the great arteries in children
Authors: Blondel De Joigny C , Metton O , Ninet J , Galoin Bertail C , Bakloul M , Perouse De Montclos T , Leconte C , Mulatier C , Di Filippo S
Published: October 2019

The objective of this study was to assess long-term outcome and factors associated wih mortality in children after arterial switch operation (ASO) for transposition of the great arteries (TGA).

Material and methods

Retrospective analysis of all ASO performed from 2000 to 2016 in patients with TGA. Demographics, clinical and biological data, surgical techniques, echocardiographic measurements, and outcomes were collected. Pronostic factors for mortality were assessed.

Results

364 patients were included (263 males). Antenatal diagnosis was made in 60,4%. Birth weight was 3207,5±511.2g, gestational age was 39.1±1.6weeks. Intramural coronary artery was present in 24 cases (6.6%). Long term follow-up was 9.2±4.8 years. Rashkind procedure was performed in 88.7% of the cases. Ventilatory support was needed in 56% and prostaglandins in 85% preoperatively. ASO occurred at the age of 7.44±6.26 days (1 to 56) and 5.6±4.6 days after admission. Bypass duration was 123.1±33.3mn. Overall and postoperative hospital stay were respectively 19.9±8.6 and 14.4±7.3 days. Survival rates were 95.3% at 1 month, 94.8% at 3, 6 and 12 months and 94.5% at 2.5 years and up to 18 years after surgery. Twenty patients died (5.5%): 17 early postoperatively (4.7%). Time from surgery to death was 64.2±207.9 days (0 to 919). Long-term events occurred in 49.6% of the patients: pulmonary stenosis, aortic or mitral regurgitation, residual shunt, coronary lesions (1.7%), arrhythmias (5.5%), cardiac failure. Freedom from late reintervention was 99.7%, 97.4%, 96.2% at 1, 3 and 6 months, 95.9%, 95%, 92.3% and 90.3% at respectively 1, 2, 5 and beyond 8 years after ASO. No Rashkind, postoperative ECMO support, delayed chest closure, bypass duration, troponine level and small birth weight were significant predictive factors of mortality (respectively p=0.006, p<0.0001, p=0.0007, p<0.0001, p=0.001 and p=0.044). Antenatal diagnosis, gender, gestational age, preoperative ventilatory support, prostaglandin infusion, and SpO2, coronary arteries anatomy or age at surgery were not associated with death.

Conclusion

This study showed that Rashkind procedure may have a favourable impact on prognosis of neonates with TGA. Postoperative ECMO support and troponine level, and small birth weight were associated with worse outcome.
P4695Pulmonary hypertension in grown-up congenital heart disease, 2018 Nice classification. Impact on mortality. GUCH Registry data
Authors: Nicolosi L N , Moros C G , Rubio M C , Pacheco Otero M , Cazalas M , Faliva G , Sosa Liprandi A , Grippo M
Published: October 2019

Background

Pulmonary hypertension (PH) is a serious complication of grown-up congenital heart (GUCH) diseases. Its onset is associated with a marked increase in mortality in these patients.

Purpose

To classify GUCH patients with pulmonary hypertension (PH) according to PH subgroups, and explore association between PH and mortality during follow up.

Methods

An observational retrospective study was conducted on patients on the GUCH database. Overall data were analyzed. Patients diagnosed with PH were selected and classified according to the 2018 Nice HT guidelines on pulmonary arterial hypertension secondary to congenital heart disease: Group 1 (PAH1) and its 4 subgroups (SG1: Eisenmenger's syndrome; SG2: left to right shunts; SG3: PAH associated with congenital heart disease; SG4: post-operative PAH); Group 2 (PH2), Group 3 (PH3), Group 4 (PH4), Group 5 (PH5). Statistical analysis: Kaplan Meier Log Rank test using SPSS 20 software.

Results

The database included 2073 patients (P), mean age 31.8±12.9 years, 54.2% (1123 P) were women. Overall mortality: 4.2% (88 P). Follow up: 44.1±37 months. Results showed 5.1% of patients (105 P) had PH, 3.8% (79 P) of whom corresponded to group PAH1, and 1.3% (26 P) to the remaining groups. Analysis of P with PH showed that 67.6% (71 P) were women, mean age was 41.3±14.7 years, mortality during follow up was 25.7% (27 P). Classification according to group showed 75.2% (79) corresponded to PAHG1, 9.5% (10) to PH2, 0% to PH3, 1% (1) to PH4, and 14.3 (15) to PH5. Analysis of P in PAHG1 showed a 43% (34 P) prevalence of SG1, 27.8% (22 P) of SG2, 8.9% (7 P) of SG3, and 20.3% (16 P) of SG4. Mortality per group was 22.8% (18 P) in PAH1, 20% (2 P)in PH2, 0% in PH 3, 0% in PH 4, and 46.7% (7 P) in PH 5. Kaplan Meier survival curves showed significant association between PH and mortality, Log Rank=0.000, and worst survival in groups PH2, PAH1 and PH5. No differences in mortality were observed among PAH1 subgroups, Log Rank= 0.458.

Survival curves

Conclusions

PH negatively affected survival of GUCHpatients. Analysis of mortality during follow up showed patients in group PH5 to have the worst outcomes, possible because patients with a single ventricle were included in this group. Group PAH1 comprised 75% of PH patients, with a greater predominance of patients with Eisenmenger's syndrome, but no significant differences in mortality during follow-up among the 4 subgroups.
P4701Impact of statin therapy on EVT for PAD with decreased low-density lipoprotein cholesterol
Authors: Noto T
Published: October 2019

Background

The benefits of treating patients with peripheral artery disease (PAD) with statins are well established. Purpose

This study investigated the effects of statins on patients who presented with low levels of low-density lipoprotein (LDL) cholesterol, were diagnosed with PAD, and subsequently underwent endovascular treatment (EVT).

Methods

We evaluated 115 cases with PAD underwent EVT, 115 cases with LDL choresterol of 100 or less. The primary outcome was Low Limb event (LLE). LLE was defined as all cause death and amputation.

Results

We divided into two groups. Statin grous N=67, non-Statin group n=48. There were no significant significant differences prevalence of male gender, diabetes mellitus, hypertension, hemodialysis and critical limb ischemia between two groups. LLE of one year in statin group was significantly lower in non-statin group. (22.5% vs 40.5% P<0.05). Kaplan-Meier curve was shown in the Figure.

Kaplan-Meier curve

Conclusion

Statin treatment in patients with PAD demonstrated beneficial effects such as less amputation, even though both groups presented with low LDL cholesterol levels.
P4703Distal radial artery access using slender technique for superfitial femoral artery intervention
Authors: Ruzsa Z , Nemes B , Orias V , Csuhajda A , Sotonyi P , Merkely B
Published: October 2019

Purpose

The purpose of this pilot study was to evaluate the acute success and complication rate of the distal radial artery access for femoral artery intervention.

Methods and results

The clinical and angiographic data of 195 consecutive cases with symptomatic superficial femoral stenosis, treated via distal radial (DR) or proximal radial (PR) access using 6F sheathless guiding between 2014 and 2018, were evaluated in a pilot study. Secondary access was achieved through the pedal artery. Primary endpoint: major adverse events (MAE), rate of major and minor access site complications. Secondary endpoints: angiographic outcome, procedural factors, cross-over rate to femoral access site, and duration of hospitalization. Overall technical success was achieved in 186 patients (95.4%) with 25/26 (96.1%) success in DR and 161/169 (95.2%) success in PR group (ns). The cross over rate to femoral access site was 3.8% in DR and 4.7% in PR group (ns), while dual (transradial and transpedal) access was used in 9/26 (34.6%) patients in DR and 39/169 (23%) patients in PR group (p<0.05). Stent implantation was necessary in 8/26 (30.7%) cases in DR and in 42/169 (24.8%) cases in PR group (ns). CTO recanalization was performed in the DR and PR group with 94.1% (16/17) and 92.6% (79/81) technical success rate. The mean contrast consumption, fluoroscopy time and procedure time was in the DR and PR group was: 93.4 [78–108]ml vs 120 [108–131]ml, 662 [501–822]vs 769 [671–866]min, and 33.4 [27–39]vs 36.5 [32–40]min (ns), respectively. The rate of access site complications in the DR and PR group was 0% and 4.7% (0% major, 4.7% minor) (p p<0.001), respectively. The cumulative incidence of MAE at 3 months in the DR and PR group was 3.8% vs 10.6% (p<0.05).

Conclusion

Femoral artery intervention can be safely and effectively performed using distal transradial access and distal radial access is associated with lower access site complications.
P4717Clinical impact of elevated tricuspid valve gradient after transcatheter tricuspid valve repair
Authors: Orban M , Orban M W , Braun D , Deseive S , Kupka D , Stocker T , Stark K , Massberg S , Nabauer M , Hausleiter J
Published: October 2019

Background

Transcatheter edge-to-edge tricuspid valve repair (TTVR) is a novel treatment approach in heart failure patients with moderate-to-severe tricuspid regurgitation (TR) at prohibitive surgical risk.

Aim

The aim of this study was to investigate the mean tricuspid valve gradient (TVG) over time and compare patient characteristics and outcome of patients with a post-procedure TVG of >3 mmHg vs. ≤3 mmHg.

Methods

All patients who were treated between between March 2016 and October 2018 with TTVR were included in this analysis. Trans-thoracic echocardiographic assessment of TVG was performed pre-procedurally, pre-discharge, after 1, 6, and 12 month.

Results

We treated 145 consecutive patients with moderate-to-severe secondary TR with TTVR. Patients were treated with TTVR for severe TR alone (70 patients) or in combination with mitral valve repair for concomitant severe mitral regurgitation and severe or moderate-severe TR with significant annulus dilatation (75 patients). One clip was implanted in 17 (11.7%), 2 clips in 83 (57.2%), 3 clips in 40 (27.6%) and 4 clips in 4 patients (2.8%). Reduction of at least 1 degree of TR was achieved in 136 Patients (93.8%). The median baseline TVG of all patients was 1 mmHg [Inter Quarter Range, IQR 1.0–1.4 mmHg]. The median TVG – measured at post-procedural trans-thoracic echocardiogram pre-discharge – increased to 2 mmHg [IQR, 1.6–3.0 mmHg] and remained constant up to 12 month (2.0 mmHg [IQR 1.0–2.0 mmHg).

Of these, twenty-five patients showed an elevated TVG >3 mmHg post-procedurally. Patients with TVG >3 mmHg were younger (73.1±11.0 vs. 77.5±9.2 years, p=0.038) and presented with lower levels of pro-BNP at baseline (median 2276 ng/l [IQR, 906–5150] vs. 4182 ng/l [2310–8629], p=0.008) compared to patients with TVG ≤3mmHg. All other baseline characteristics were balanced. There were no differences in procedural success (TR reduction of ≥1 grade in 96% vs. 93.3%, p=0.946) and number of clips implanted (p=0.697). At one month follow-up there were no differences in NYHA class (NYHA class ≥3 in 24% vs. 30.8%, p=0.559), quality of life measured with the Minnesota Living With Heart Failure questionnaire (32.0±22.9 vs. 31.1±16.3, p=0.833), 6 minute walking distance (255.5±140.6 vs. 250.5±111.7 metre, p=0.872). The clinical endpoints 1-year mortality (HR 1.07; 95% CI [0.43–2.65], p=0.88) and the combined endpoint mortality and hospitalization for heart failure at one year (HR 1.07; 95% CI [0.46 to 2.48], p=0.88, see Figure) did not differ between patients with a TVG >3 mmHg vs. patients with a TVG ≤3mmHg.

Figure 1

Conclusion

TTVR results in a small increase in the tricuspid valve gradient, which remains constant up to one year. A small cohort of patients shows an elevated TVG higher than 3 mmHg after the procedure. This elevation has no impact on NYHA class at 1 month and the clinical endpoints mortality and hospitalization for heart failure at 1 year.
P4736The Prognostic Impact of Volume Substitution on Cardiac Strain and the Development of Postoperative Atrial Fibrillation after Cardiac Surgery
Authors: Sulzgruber P , Pilz A , Schnaubelt S , Koller L , Kazem N , Hammer A , Laufer G , Steinlechner B , Fleck T , Toma A , Wojta J , Niessner A
Published: October 2019

Background

Postoperative atrial fibrillation (POAF) represents a common complication after cardiac valve or coronary artery bypass surgery. Etiologically, multifactorial causes such as the patients' age, weight, comorbidities or local remodeling proved a strong association with this common arrhythmia. While strain of atrial tissue is known to induce atrial fibrillating impulses, less attention has been paid to potentially strain-promoting values during the peri- and post-operative period. Therefore, we aimed to determine the association of peri- and post-operative volume substitution on markers of cardiac strain and subsequently its impact on the promotion and development of POAF.

Methods

In this prospective observational study 271 patients undergoing elective cardiac surgery in our Medical University were enrolled (median age: 69 years [IQR: 60–75 years]; 195 [72%] male gender). Intra- and post-operative data was collected from anesthesiologic and intensive care unit protocols. Multivariate binary logistic regression analysis was used to identify the prognostic value of volume substitution on the development of POAF.

Results

A total of 123 (45.4%) individuals developed POAF. The average intra-operative transfusion volume was significantly elevated in the POAF subgroup (605.6ml [POAF] vs. 227.1ml [non-POAF]; p<0.001). Moreover, the fluid balance within the first 24 hours after surgery was significantly higher in patients developing POAF (+1129.6 ml [POAF] vs. +544.9 ml [non-POAF]; p=0.044). We found that N-terminal pro brain natriuretic peptide (NT-proBNP) values were significantly elevated in patients that received any volume substitution (2860.0 pg/mL [Transfusion] vs. 1486.5 pg/mL [no-Transfusion]; p=0.002). In line with those results, the postoperative fluid balance was also found to have a direct and significant correlation with postoperative NT-ProBNP values (r=0.287, p=0.002). Of note, the amount of substituted volume proved to be a strong and independent predictor for POAF with an adjusted odds-ratio (OR) per one standard deviation (1-SD) of 2.49 (95% CI: 1.25–4.96; p=0.009).

Conclusion

Within the present analysis we were able to demonstrate that substitution of larger transfusion volumes presents a strong and independent predictor for the development of POAF. Via the observed distinct association with NT-proBNP values, it can reasonably be assumed that post-operative atrial fibrillating impulses are triggered via volume-induced cardiac strain.
P4737Complete surgical revascularization: the impact of the different definitions on mortality
Authors: Veiga Oliveira P , Madeira M , Ranchordas S , Brizido C , Nolasco T , Boshoff S , Marques M , Almeida M , Teles R , Calquinha J , Sousa-Uva M , Ventosa A , Abecassis M , Neves J P
Published: October 2019

Introduction

The concept of complete revascularization arises from the early stages on coronary artery bypass grafting (CABG). There are several different definitions applied across the literature, promoting a difficult comparison between studies. Despite the established importance of complete revascularization, there is no agreement which definition has the most impact on mortality.

Objectives

Evaluate the impact of the different definitions of complete surgical revascularization in late mortality.

Methods

Single center retrospective study of all consecutive patients submitted to isolated CABG with previous myocardial viability assessment (myocardial perfusion scintigraphy) from 2011 to 2016. Exclusion criteria: emergent procedures and previous cardiac surgery. The primary end-point was follow-up mortality (n=20). The population of study was162 patients with 22,2% female gender and a mean age of 66 years. The follow-up was complete in 98,8%, median time of 4,1 (IQR 3,0–5,5) years.

The completeness of revascularization was classified in all patients according to four different definitions (n=162 for each definition): Numerical (the number of stenotic vessels must equal the number of distal anastomoses applied); Functional (all ischemic myocardial territories are reperfused; areas of old infarction with no viable myocardium are not required to be reperfused); Anatomical Conditional (all stenotic main-branch vessels are revascularized) and Anatomical Unconditional (all stenotic vessels are revascularized, irrespective of size and territory supplied).

For each definition, statistical analysis was performed using the Kaplan-Meier method with log rank test and Cox proportional analysis (EuroSCORE II and revascularization definition).

Results

On univariate analysis, there was no significant statistical association between each definition of complete revascularization and follow-up mortality: numerical (p=0,694); anatomical unconditional (p=0,294); but a trend was found on functional (p=0,063) and anatomical conditional (p=0,084).

On multivariate analysis, incomplete functional revascularization increased the risk of follow-up mortality in 2,89 folds and anatomical conditional in 3,28 folds (Figure 1). The other definitions were not statistically associated with late mortality.

Conclusion

According to this study, complete functional and anatomical conditional revascularization definitions are determinants of follow-up mortality in a multivariate model including EuroScore II. The revascularization of all stenotic main-branch vessels (anatomical conditional) seems to have the highest impact, fact that we should be taken in consideration on daily work.
P4753Impact of renal function on bleeding risk in patients with non-valvular atrial fibrillation treated with direct oral anticoagulants: Subanalysis of the DIRECT registry
Authors: Hirata A , Sotomi Y , Kobayashi T , Amiya R , Hirayama A , Higuchi Y
Published: October 2019

Background

Renal dysfunction is one of the high bleeding risk factors in patients with atrial fibrillation as presented in the HAS-BLED score. The impact of renal function on bleeding risk is, however, still to be investigated in the era of direct oral anticoagulants (DOAC).

Methods

We conducted a single-center prospective observational registry of NVAF patients with DOACs: the DIRECT registry (UMINehz745.112933283). All patients with NVAF (N=2216) who were users of dabigatran (N=648), rivaroxaban (N=538), apixaban (N=599), or edoxaban (N=431) from 2011 to 2017 were enrolled (71.6±10.8 years, mean follow-up duration: 407.2±388.3 days). In the present substudy, all patients were stratified by renal function. Creatinine clearance (CCr) was estimated with the Cockcroft-Gault equations with available creatinine at baseline. Patients were divided into 4 groups based on CCr. (CCr>80, CCr50–80, CCr30–50, and CCr<30). The primary endpoint was major bleeding according to the ISTH criteria. Clinical endpoints were compared between the groups (Kaplan-Meier analysis, Log-rank test). The influence of DOAC type in patients with renal dysfunction was also assessed for the primary endpoints of major bleeding.

Results

Kaplan-Meier estimated 2-year major bleeding rate significantly increased as renal function decreased (CCr>80 2.5%, CCr50–80 4.2%, CCr30–50 4.2%, CCr<30 7.8%, Log-rank test p<0.001). However, in patients with apixaban (low CCr 59.6±25.9ml), major bleeding does not appear to increase as renal function decreased.(CCr >80 9.2%, CCr 50–80 8.0%, CCr 30–50 10.3%, CCr<30 7.3%, Log-rank test p=0.97).

Kaplan-Meier Analysis

Conclusions

Renal dysfunction increased bleeding risks in NVAS patients with DOACs. Apixaban might be safely used for patients with renal dysfunction.
P4755Sex differences in admission rates, use of anticoagulation, and outcomes for emergency department presentations of atrial fibrillation
Authors: Daniele P , Dover D C , Islam S , Hawkins N , Kaul P , Sandhu R K
Published: October 2019

Background

Studies in non-Emergency Department (ED) settings have shown women with non-valvular atrial fibrillation (NVAF) differ in presentation, treatment, and outcomes compared to men. Despite AF being a common reason for ED visit, little is known regarding sex differences in patients presenting to ED.

Purpose

We sought to determine whether sex differences exist in rates of admission among NVAF patients presenting to the ED and if oral anticoagulant (OAC) use and outcomes differ by ED discharge status.

Methods

Patients≥18 years old, presenting to the ED with incident NVAF in two western Canadian provinces (Alberta and British Columbia) from April 2012 to March 2015 were included. ED records were linked to hospital records to identify patients admitted to hospital versus discharged from the ED. Outcomes of interest were 30-day mortality and 1-year stroke, heart failure (HF) and mortality. Pharmaceutical claims were queried for OAC use within 90 days following NVAF ED event.

Results

Of 16,991 ED NVAF patients, 7,770 (46%) were women and 9,221 (54%) were men (p<0.001). Compared to men, women were older (73.9 vs 65.6 years, p<0.001) and presented with higher CHA2DS2-VASc scores (4.0 vs 2.0, p<0.001). Overall, 41% of women and 37% of men were admitted to hospital (p<0.001). OAC rate was 50% among admitted and 37% among discharged (p<0.001). OAC rates were 53% in women and 48% in men among admitted (p<0.001), and 39% in women and 35% in men among discharged (p<0.001). OAC rates were higher in patients with CHA2DS2-VASc ≥1 who were admitted (53% in women (n=2,781) and 52% in men (n=2,683), p=0.63) than in those who were discharged (39% in women (n=4,435) and 45% in men (n=3,866), p<0.01). Women had higher rates of mortality at 30-days and 1-year, and stroke at 1-year compared to men, irrespective of ED discharge status (all p<0.02). Women admitted had higher HF rates at 1-year compared to men (p=0.002). (Table)

Outcomes by Sex and ED Discharge Status Outcome Discharged Admitted Women (N=4,560) Men (N=5,780) p-value Women (N=3,210) Men (N=3,441) p-value 30 Day Mortality, n (%) 63 (1.4) 50 (0.9) 0.01 261 (8.1) 228 (6.6) 0.019 1 Year Mortality, n (%) 270 (5.9) 248 (4.7) <0.001 717 (22.3) 604 (17.6) <0.001 Stroke*, rate (SE) 1.7 (0.19) 0.9 (0.13) <0.001 4.0 (0.37) 2.6 (0.28) 0.001 Heart Failure*, rate (SE) 3.6 (0.28) 3.1 (0.23) 0.16 12.9 (0.62) 10.4 (0.54) 0.002 *Censored on death.

Conclusions

In this population-based study of patients presenting to ED with NVAF, we found women were more likely to be admitted to hospital than men. Women had a worse prognosis than men, irrespective of ED discharge status. Use of OAC was suboptimal, regardless of patient sex.

Acknowledgement/Funding

Heart and Stroke Foundation of Canada, UBC Cardiology, Servier Alberta Innovation Health Fund
P4757Vitamin k antagonists are associated with higher risk of osteoporotic fractures compared to non-vitamin k antagonist oral anticoagulants among atrial fibrillation patients: a nationwide cohort study
Authors: Binding C , Olesen J B , Abrahamsen B , Staerk L , Gislason G , Bonde A N
Published: October 2019

Background/Introduction

Osteoporotic fractures are associated with high mortality and reduced life quality in an elderly population. Several studies report an increased risk of fractures among patients treated with oral anticoagulants (OAC), however, only sparse research has been made to clarify the difference between treatment with vitamin K antagonists (VKA) and non-VKA oral anticoagulants (NOACs) regarding the risk of osteoporotic fractures.

Purpose

The purpose of this study was to evaluate the risk of osteoporotic fractures among patients with atrial fibrillation (AF) in long-term VKA or NOAC treatment.

Methods

Patients with AF were identified using Danish national registries and were included when they had undergone 180 days OAC treatment, and only if they had no prior use of osteoporosis medication. The study period was from 1 January 2013 until 30 June 2017, and patients were followed for 2 years, or until death, outcome or emigration. Outcomes were hip fracture, major osteoporotic fracture, any fracture, initiation of osteoporosis medication, and a combined endpoint. G-formula was used to determine standardized absolute risk, and multiple covariate adjusted Cox regressions were used to calculate hazard ratios (HR).

Results

Overall, 37,350 patients with AF were included; 32.6% received VKA treatment (median age 72 years, 61.8% men) and 67.4% received NOAC treatment (median age 73 years, 55.9% men). The standardized absolute 2-year risk of any fracture was low among NOAC treated patients (3.1%; 95% CI: 2.9% to 3.3%), and among VKA treated patients (3.8%; 95% CI: 3.4% to 4.2%).

NOAC was associated with a significantly lower relative risk of any fracture (HR: 0.85; 95% CI: 0.74 to 0.97), of major osteoporotic fractures (HR: 0.85; 95% CI: 0.72 to 0.99), and of initiating osteoporotic medication (HR: 0.82; 95% CI: 0.71 to 0.95). A combined endpoint showed that patients treated with NOAC had a significantly lower risk of suffering from any fracture or initiating osteoporosis medication (HR: 0.84; 95% CI: 0.76 to 0.93).

Adjusted relative two-year risks

Conclusion

In a nationwide population, the absolute risk of osteoporotic fractures was low among AF patients on OAC, but NOAC was associated with a significantly lower risk of osteoporotic fractures compared to VKA.

Acknowledgement/Funding

Scholarship from The Copenhagen University Hospital Herlev and Gentofte
P4777Mortality in patients with non-valvular atrial fibrillation in South America. Warfarin has significant higher global mortality rates versus dabigatran and rivaroxaban
Authors: Arocena M J , Vanerio G
Published: October 2019

Background

Oral anticoagulants are the cornerstone for the management of atrial fibrillation (AF) to reduce cardioembolic stroke

Randomized controlled trials of anticoagulants have shown non-inferiority of direct oral anticoagulants (DOACs) compared to warfarin

Most DOACs represent an advance in therapeutic safety when compared to warfarin for prevention of thromboembolism in patients with AF.

Objectives

Determine long term survival, total mortality rates and mortality cause between patients with non-valvular atrial fibrillation (AF) receiving anticoagulants (warfarin, dabigatran and rivaroxaban)

Methods

Retrospective analysis of consecutive patients with AF receiving anticoagulants in two Hospitals in Montevideo, using electronic registries. Demographics, co-morbidities, CHA2DS2VASc scores and mortality cause were annotated. Follow-up started on Jan 2011 and finished on Dec 2017. Anticoagulation quality was expressed as the standard deviation of INRs (SD-INRs). We performed global mortality and mortality cause analysis on patients with anti-VitK versus direct anticoagulants.

Statistical analysis: Survival analysis was performed using Kaplan-Meier (log rank) and Cox regression model. All differences between groups were considered significant if the p value was <0.001.

Results

We studied 4501 pts., 3627 patients were on warfarin (80.6%), 456 (10.1%) were on dabigatran and 418 (9.3%) on rivaroxaban. Those receiving direct anticoagulants were older, 79±9 vs 77±11 years, (p=0.0001), 51.3% were female, with a significantly higher prevalence of HTN; 93.7% vs 88.8% and a CHA2DS2VASc score ≥2 (96% vs 91%), and a lower prevalence of CHD (5.8% vs 10.4%), CHF (3.7% vs 9.5%) and CKD (2.3% vs 6.3%).Total mortality was 818 (18%); patients receiving warfarin had significantly higher mortality rates, 727 (20.1%) vs 91 (10.4%); 63 and 28 (13.8%, 6.7% dabigatran and rivaroxaban respectively) Kaplan-Meier curves were significantly different (Figure 1) showing higher survival rates for those on DOACs. The SD-INRs were 0.85±0.47 (n=1726 alive) vs 1.05±0.46 (n=548 dead), mean difference 0.2 (99% CI 0.14–0.26). Mortality could be analysed in 759 patients (92,7%). The most important cause of death was cardiovascular disease in 26.5%. We could not find significant differences in the cause of death between groups. Using Cox regression model, variables with significant increased mortality were HTN, CHD, CHF, CKD and history of previous CVA. The only variable with a significant decrease in mortality was the use of dabigatran or rivaroxaban; HR 0.55 (95% CI 0.44–0.69)

Figure 1

Conclusions

In this large cohort of patients, those receiving warfarin have significantly higher mortality rates. Mortality differences were not related to stroke or major bleeding but could be explained by a higher prevalence of CHD, CHF and CKD in the warfarin group despite a significant lower CHA2DS2VASc score.
P4778Effectiveness and safety of rivaroxaban versus warfarin in nonvalvular atrial fibrillation patients with coronary or peripheral artery disease
Authors: Coleman C I , Sood N , Bunz T J , Eriksson D , Meinecke A.-K , Baker W J
Published: October 2019

Background

The efficacy and safety of rivaroxaban use for the prevention of major thrombotic vascular events (MTVEs) has been demonstrated in randomized trials of nonvalvular atrial fibrillation (NVAF), coronary artery disease (CAD) and peripheral artery disease (PAD) patients.

Purpose

To assess the effectiveness and safety of rivaroxaban versus warfarin in preventing MTVEs in NVAF patients with concomitant CAD and/or PAD in routine practice.

Methods

Using MarketScan data from 1/2012–12/2017, we identified oral anticoagulant (OAC)-naïve NVAF patients with comorbid CAD and/or PAD and ≥12-months of insurance coverage before OAC initiation. Differences in baseline covariates between cohorts were adjusted using inverse probability-of-treatment weights based on propensity-scores (standardized differences <0.1 achieved for all covariates after adjustment). The primary effectiveness endpoint was the composite of any MTVE including ischemic stroke, myocardial infarction or adverse limb event (revascularization or amputation). The primary safety endpoint was major bleeding defined using the Cunningham algorithm. Patients were followed until a MTVE, discontinuation or switch of index OAC, insurance disenrollment or end-of-data availability. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing the cohorts were calculated using Cox regression.

Results

We identified 3,257 rivaroxaban (30.4% received a reduced dose) and 5,046 warfarin users with NVAF and comorbid CAD and/or PAD. Median (25%-75% range) age was 74 (65–81) years, CHA2DS2-VASc score was 3 (2–4). Rivaroxaban was associated with a 32% (95% CI=8–50%) reduction in the composite of any MTVE (Figure). No significant difference in major bleeding was observed (HR=1.13, 95% CI=0.84–1.52).

Figure 1. Event Rates and Hazard Ratios

Conclusions

In patients with NVAF and comorbid CAD and/or PAD treated in routine practice, rivaroxaban use appears to reduce patients' risk of MTVEs compared to warfarin, without increasing their risk of major bleeding. This study lends further support to RCT findings that suggest rivaroxaban is effective in preventing major events in multiple vascular beds.

Acknowledgement/Funding

Bayer AG, Berlin, Germany
P4795Comparative safety of factor-xa inhibitors vs phenprocoumon in patients with non-valvular atrial fibrillation and renal disease - insights from the RELOADED study
Authors: Bonnemeier H , Kreutz R , Enders D , Schmedt N , Vaitsiakhovich T , Kloss S
Published: October 2019

Background

Data on safety of Factor-Xa inhibitors and phenprocoumon in patients with non-valvular atrial fibrillation (NVAF) and renal disease is scarce. Among others, our study aimed to investigate the safety risks of fatal bleeding and intracranial haemorrhage (ICH) in new users of Factor-Xa inhibitors vs. phenprocoumon, the vitamin-K antagonist (VKA) of choice in Germany.

Methods

We conducted a new user cohort study (one year washout period) in patients with NVAF and renal disease. German claims data between January 1st, 2013 and June 30th, 2017 were utilized and a multiple Cox-regression was performed to calculate confounder-adjusted hazard ratios (HRs) for the risk of fatal bleeding and ICH in Factor-Xa inhibitors and phenprocoumon initiators. Additionally, a propensity score matching and an inverse probability of treatment weight analysis were performed as sensitivity analyses. Cases of fatal bleeding were defined as hospitalization with a primary hospital discharge diagnoses for bleeding with documented death as reason for hospital discharge or within 30 days after hospital discharge.

Results

The overall population comprised 23,552 phenprocoumon initiators, 22,338 rivaroxaban initiators and 16,201 apixaban initiators, where the number of patients with renal disease initiating these agents were 7,289 for phenprocoumon, 5,121 patients for rivaroxaban 15mg or 20mg and 4,750 patients for apixaban 2.5mg or 5mg, respectively. In the confounder-adjusted analysis, a beneficial effect for rivaroxaban and apixaban over phenprocoumon was observed for the risk of ICH and fatal bleeding (figure 1) for both the overall and renal disease population. Hazard ratios for rivaroxaban and the risk of ICH were calculated as 0.57 (0.43; 0.75) for the overall population and 0.62 (0.37; 1.01) for the renal disease population where hazard ratios for apixaban were calculated as 0.43 (0.31; 0.60) for the overall population and 0.41 (0.23; 0.74) for the renal disease population, respectively. There was not sufficient data to conduct the analyses for edoxaban.

Figure 1

Conclusion

This large retrospective database study conducted in Germany confirms the safety profile of rivaroxaban and apixaban over VKA in patients overall and specifically in patients with renal disease when assessing the risk of ICH and fatal bleeding. Our study adds evidence in a relevant subgroup of patients where anticoagulation is often challenging.

Acknowledgement/Funding

This study was funded by Bayer AG
P4797Genetic testing in 101 consecutive lone atrial fibrillation patients is able to identify a subgroup with increased severity
Authors: D'Arezzo Pessente G , Darrieux F D , Sacilotto L S , Olivetti N O , Wulkan F W , Oliveira T O , Hachul D H , Wu T W , Scavacca M S , Krieger J K , Pereira A P
Published: October 2019

Introduction

Atrial fibrillation (AF) is the most common arrhythmia and the cause of 15% of all strokes and up to 6% of medical admissions. It is estimated that currently about 2.0 million Brazilians, and 30 million individuals worldwide, are affected by the disease. It is a complex and multifactorial disease, and the mechanisms are still not well understood. Between 10–20% of AF patients do not have any known predisposing factors, a condition once called “lone AF”. The role of genetic testing still remains controversial in this clinical scenario.

Purpose

The aim of this study was to identify the occurrence of pathogenic genetic variants in patients with atrial fibrillation without known risk factors.

Methods

In a tertiary hospital, 101 young patients with apparent “lone AF” were screened with genetic testing by NGS using a custom genetic panel with 159 channelopathy and cardiomyopathy related genes. Variants found were classified according to the American College of Genetic and Genomic (ACMG) criteria. Subjects were evaluated with clinical and familial history, electrocardiogram, 24 hours Holter monitoring, echocardiogram, cardiac MRI and treatment response. Multivariate analyses were performed by logistic linear regression model.

Results

During an inclusion period of 4 years, 101 consecutive patients, with mean age of 38.6 years old, were classified as “lone AF” (78% male); 76% presented paroxysmal AF and 24% persistent/permanent AF. Family history of early sudden death (bellow 60 years old) was reported in 37% of cases (78% below 50 years old); 10% had family members with pacemakers; and 44% reported having family members with early AF onset. Genetic testing demonstrated that 14/101 (13.8%) of patients presented genetic variants classified as pathogenic or likely pathogenic (P/LP) according to ACMG criteria. The genes most frequently affected were LMNA (3/101), ANK2 (3/101) and truncating variants in TTN (3/101). Two variables were significantly associated with harboring a pathogenic mutation: family history of sudden death (OR: 5.58; 1,19–26,12 CI; p=0.029) and pacemaker reported in the family history (OR: 6.83; 1.11–42.04 CI; p=0.038).

Conclusion

Our data showed that approximately 15% of “lone AF” patients are carriers of known pathogenic mutations in genes associated with inherithed cardiomyopathy. In addition, we show that being a carrier is potentially associated with a more severe phenotype. These findings suggest that genetic testing in “lone AF” patients may be able to identify a subgroup with a more severe phenotype are for whom a different management strategy might be indicated.

Acknowledgement/Funding

National Council for Scientific and Technological Development (CNPq)
4879Is intensive blood pressure strategy effective and safe in patients with cardiovascular disease? The two sides of the coin
Authors: Vlachopoulos C , Terentes-Printzios D , Aznaouridis K , Ioakeimidis N , Xaplanteris P , Lazaros G , Tousoulis D
Published: October 2019

Background/Lntroduction

Recent data advocate the adoption of a more intensive treatment strategy for the management of blood pressure (BP).

Purpose

We sought to investigate whether the overall effects of the Systolic Blood Pressure Intervention Trial (SPRINT) are applicable to cardiovascular disease (CVD) patients.

Methods

In the present post-hoc analysis we analyzed data from SPRINT that randomly assigned 9361 individuals to systolic blood pressure (SBP) target of less than 120 mm Hg (intensive treatment) or a target of less than 140 mm Hg (standard treatment). 1562 patients had clinically evident CVD (age=70.3±9.3 years, 24% females) at study entry and were followed for 3.1 years. Further, we assessed the effect of low (<150 mm Hg) baseline SBP on clinical endpoints.

Results

In CVD patients, there was no benefit from the intensive treatment regarding all endpoints, except for a marginally significant benefit on all-cause mortality (hazard ratio [HR]: 0.67; 95% confidence interval [CI], 0.45 to 1.00; P=0.0509) (Figure). Further, while there was no increase in serious adverse events (SAE) in the intensive group, there was an increased HR for study-related SAE in the intensive management group (HR: 2.00; 95% CI: 1.22 to 3.26; p=0.006), a greater incidence of acute renal failure (HR: 1.57; 95% CI: 1.01 to 2.44; P=0.044), electrolyte abnormalities (HR: 1.77; 95% CI: 1.03 to 3.02; P=0.038) and specifically hyponatremia (HR: 2.24; 95% CI: 1.13 to 4.46; p=0.021). In patients with low baseline SBP there was a beneficial effect on all-cause mortality (HR: 0.56; 95% CI: 0.33 to 0.96; P=0.033), but with greater stroke incidence (HR: 2.94; 95% CI: 1.04 to 8.29; P=0.042). As far as adverse events are concerned, patients with SBP<150 mm Hg had increased risk only for study-related SAE and electrolyte abnormalities.

Survival curves for the main endpoints

Conclusions

We confirm the beneficial effect of the intensive strategy in SPRINT study on all-cause mortality and the harmful effect on other than serious adverse outcomes in patients with CVD. However, in patients with low baseline SBP stroke increases.

Acknowledgement/Funding

This manuscript was prepared using SPRINT_POP Research Materials obtained from the National Heart, Lung, and Blood Institute