bluuebunny/crossref_metadata_2025_split huggingface dataset:
54Role of the gut microbiome for the cholesterol lowering effect of atorvastatin
Authors: Zimmermann F , Schmidt D , Escher U , Jasina A , Roessler J , Heimesaat M M , Gast M , Poller W , Kratzer A , Giral Arnal H , Schumann P , Leistner D M , Landmesser U , Haghikia A 
Published: October 2019

Abstract

Background and aims
Statins show interindividual differences in the extent of low-density lipoprotein cholesterol (LDL-C) reduction. The mechanisms of this interindividual variation are not fully understood. Here, we examined the potential role of the gut microbiome for the LDL-C lowering property of atorvastatin.

Methods
Mice (C57BL/6) with either intact (conventional mice, CONV, n=24) or with antiobiotic depleted gut microbiome (gnotobiotic, n=16), were put on standard chow diet (SCD) (n=11) or high fat diet (HFD) (n=29) for 6 weeks. During the last 4 weeks atorvastatin (Ator, 10mg/kg body weight/day) or control vehicle was orally applied via gavage. Blood levels of LDL-C and glucose and body weight after 6 weeks of treatment were compared between the groups. Expression of genes involved in hepatic and intestinal cholesterol-metabolism were examined. Faeces of CONV mice were analyzed for alteration of the gut microbiota profile upon atorvastatin treatment using 16S rRNA qPCR.

Results
HFD fed mice with intact gut microbiome showed significantly increased blood LDL-C levels as compared to SCD (HFD: 36.8±1.4 mg/dl vs. SCD: 22.0±1.8 mg/dl; P<0.01). Bodyweight gain or blood glucose levels after HFD were not significantly different between CONV and gnotobiotic mice. While in CONV mice atorvastatin significantly reduced LDL-C levels after HFD, in gnotobiotic mice the LDL-C lowering effect of atorvastatin was attenuated (CONV+HFD+Ator: 31.0±1.8 mg/dl vs. gnotobiotic mice+HFD+Ator: 46.4±3 mg/dl; P<0.01). The expression of genes involved in hepatic cholesterol synthesis was not significantly altered in gnotobiotic mice as compared to CONV mice. In CONV mice HFD decreased the relative abundance of the bacterial phyla Bacteroidetes and increased the abundance of Firmicutes as compared to SCD. The ratio between Firmicutes to Bacteroidetes was shifted towards control conditions upon atorvastatin treatment.

Conclusions
The results of this study suggest a regulatory impact of atorvastatin on the gut-microbial profile and, in turn, a crucial role of the gut-microbiome for the LDL-C lowering effect of atorvastatin independent of its regulation of hepatic cholesterol synthesis. Our findings provide novel insight into potential microbiota-related mechanisms causing interindividual variation in LDL-C lowering effects of statins.

Acknowledgement/Funding
German Heart Research Foundation
79Experience from heart or heart/lung transplantation from a single centre for adult congenital heart disease: too little, too late?
Authors: Meras Colunga P , Riesgo Gil F , Khan U , Pires A , Smith J , Kempny A , Simon A , Gatzoulis M A 
Published: October 2019

Abstract

Introduction
Heart failure is the leading cause of death in adults with congenital heart disease (ACHD). Heart or heart and lung transplantation (H/HLTx) can be effective therapy for these patients, but unfavourable anatomy, end-organ damage, pulmonary vascular disease, HLA sensitization and lack of robust selection criteria currently limit its application.

Methods
Consecutive ACHD patients >16 years of age who were considered for H/HLTx at our tertiary centre between 2006 and 2018 constitute our study population. Baseline characteristics and outcome, including H/HLTx and death were obtained for all from designated databases, medical records and the UK Office for National Statistics.

Results
Of a total of more than 9,000 active ACHD patients, 130 (53.1% male, mean age 42.2, IQR 32.6–50.2 years) fulfilled inclusion criteria with a broad spectrum of underlying ACHD and considerable mortality across all anatomic subgroups [Table 1].
82% of patients had previous cardiac surgery (55.5% with ≥2 sternotomies or thoracotomies). Cardinal presenting features were poor functional capacity, low cardiac output, cyanosis and/or end-organ disease; “only” 47% had moderate or severe dysfunction of the systemic and 37% of the subpulmonary ventricle. Frequent comorbidities were atrial arrhythmia 68.7%, PH 30.4%, CKD 23.5%, liver dysfunction or cirrhosis 11.3%; 36.8% of patients had an ICD and 16.5% a CRT, whereas 79.8% were on diuretics, 70.5% MRA, 51.6% beta blockers, 32.6% ACEI, 18.9% ARB, 10.5% Digoxin and 29.5% on pulmonary vasodilators. HLA antibodies were positive in 47.3% (high sensitization >90% in 13.2%).
There was high overall mortality with 35.4% of patients dying over a median of 2.7 years (IQR 1.1–4.9). Only 13.6% from our cohort were transplanted, with a survival of 76.5% at a mean of 5.9 years from H/HLTx.
ACHD subgroup % of total % transplanted Mortality (%) Median follow-up (years) Univentricular heart 25.4 6.1 30.3 2.5 Systemic RV 21.5 7.4 35.7 2.6 Shunts with PAH / Eissenmenger 13.9 5.9 27.8 3 Tetralogy of Fallot with Pulmonary atresia 12.3 14.3 50 3.5 Left sided valvar disease, CoA, Marfan 10.8 14.3 50 0.6 CHD associated with cardiomyopathy 9.2 50 33.3 5.3 Other 6.9 22.2 22.2 2.2 RV: right ventricle; PAH: Pulmonary arterial hypertension; CoA: aortic coarctation.
Survival in end-stage heart failure

Conclusion
Of the small number of patients with heterogenous ACHD considered for H/HLTx in our contemporary practice, there was high overall mortality, whereas only a fraction of patients was actually transplanted. Better patient selection and timing are clearly warranted so that more ACHD patients benefit from this effective therapy.

Acknowledgement/Funding
None
95TAVI performed without systematic intensive care unit admission: an update of a single center experience
Authors: Akodad M A , Aldhaheri E A , Macia J C M , Gandet T G , Schmutz L S , Marin G M , Rivalland F R , Robert G R , Targosz F T , Maupas E M , Albat B A , Cayla G C , Leclercq F L 
Published: October 2019

Abstract

Background
Systematic admission to the intensive care unit (ICU) was considered as a standard of care after transcatheter aortic valve implantation (TAVI). However, regarding to improvements in procedural results, our team pointed out feasibility and safety of TAVI without ICU admission in selected patients referred in our center in 2015

Purpose
The aim of this study was to evaluate the evolution of our practice after the first study to confirm the feasibility and safety of TAVI without ICU in a large population of patients.

Methods
We evaluate prospectively 451 consecutive patients undergoing TAVI between January 2017 and december 2017. The same “low-risk” criteria were applied to this cohort of patients to allow admission to conventional cardiology unit: stable clinical state, transfemoral access, no right bundle branch block at baseline, left ventricular ejection fraction >40% and no complications occurring during the procedure. Any new conduction disturbance was considered as indication for ICU.

Results
The mean age was 81.8±7.5 years and the mean logistic Euroscore was 9.1±3.3%. The balloon-expandable Sapien 3 was used in 181 patients (40.1%) and the transfemoral route was the main vascular approach (n=412, 91.3%). According to the predefined criteria, 289 patients (64.1%) were considered at “high-risk”. In-hospital major complications occurred in 52 patients (11.5%) including 3 deaths (0.7%), 6 major vascular complications (1.3%), 1 stroke (0.2%), 7 heart failures (1.5%), 2 tamponades (0.4%), 2 ventricular perforations (0.4%) and 31 high-degree conduction disorders (6.9%) including 26 patients undergoing immediate pacemaker implantation allowing a non-ICU decision. All complications occurred in the “high-risk” group (figure) and the negative predictive value of the “low-risk” criteria to predict complications was 100%. In multivariate analysis, right bundle branch block (p<0.ehz747.00241), first degree atrioventricular block (p=0.02), low LVEF (p=0.01) were found as pre procedural predictive factors of adverse events.
ICU and non-ICU admission after TAVI

Conclusion
Our results confirm that with a rigorous selection of patients and using simple criteria, TAVI can be routinely performed without ICU admission in nearly 40% of patients with a stable proportion of patients not referred to ICU between 2015 and 2017.
124Impact of intimal tracking for recanalization of CTO lesions on long-term clinical outcomes
Authors: Kano S , Nasu K , Habara M , Shimura T , Yamamoto M , Adachi Y , Konishi H , Kodama A , Koshida R , Kinoshita Y , Tsuchikane E , Terashima M , Matsubara T , Suzuki T 
Published: October 2019

Abstract

Background
For recanalization of coronary chronic total occlusion (CTO) lesions, subintimal guidewire tracking in both antegrade and retrograde approaches are commonly used.

Purpose
This study aimed to assess the impact of subintimal tracking on long-term clinical outcomes after recanalization of CTO lesions.

Methods
Between January 2009 and December 2016, 474 CTO lesions (434patients) were successfully recanalized in our center. After guidewire crossing in a CTO lesion, those lesions were divided into intimal tracking group (84.6%, n=401) and subintimal tracking group (15.4%, n=73) according to intravascular ultrasound (IVUS) findings. Long-term clinical outcomes including death, target lesion revascularization (TLR), target vessel revascularization (TVR) were compared between the two groups. In addition, the rate of re-occlusion after successful revascularization was also evaluated.

Results
The median follow-up period was 4.7 years (interquartile range, 2.8–6.1). There was no significant difference of the rate of cardiac death between the two groups (intimal tracking vs. subintimal tracking: 7.0% vs. 4.1%; hazard ratio, 0.61; 95% confidence interval [CI], 0.19 to 2.00; p=0.41), TLR (14.3% vs. 16.2%; hazard ratio, 1.34; 95% CI, 0.71 to 2.53; p=0.37), and TVR (17.5% vs. 20.3%; hazard ratio, 1.27; 95% CI, 0.72 to 2.23; p=0.42). However, the rate of re-occlusion was significantly higher in the subintimal tracking group than intimal tracking group at 3-years re-occlusion (4.2% vs. 14.5%; log-rank test, p=0.002, Figure). In the multivariate COX regression, subintimal guidewire tracking was an independent predictor of re-occlusion after CTO recanalization (HR: 5.40; 95% CI: 2.11–13.80; p<0.001).
Figure 1

Conclusions
Subintimal guidewire tracking for recanalization of coronary CTO was associated with significantly higher incidence of target lesion re-occlusion during long-term follow-up period.
193Qualifying event proximity, cardiovascular risk, and benefit of empagliflozin in patients with type 2 diabetes and stable atherosclerosis in the EMPA-REG OUTCOME trial
Authors: Udell J , Zinman B , Wanner C , Von Eynatten M , George J T , Zwiener I , Lund S S , Hantel S , Fitchett D 
Published: October 2019

Abstract

Background
In type 2 diabetes, the temporal proximity of an atherosclerotic cardiovascular (CV) event can impact prognosis, but whether timing influences sodium glucose co-transporter 2 inhibitor effects is unknown. We explored the association of time from last qualifying CV event before randomisation (myocardial infarction [MI], stroke, coronary artery disease or peripheral arterial disease) with CV outcomes and benefit of empagliflozin (EMPA) in EMPA-REG OUTCOME.

Methods
Patients (pts) were randomised to EMPA 10 mg, 25 mg or placebo and followed for 3.1 years (median). Risk of major adverse CV events (3P MACE: CV death, MI, stroke), CV death or hospitalisation for heart failure (HHF) were evaluated using Cox regression in subgroups of ≤1/>1 year since last qualifying CV event. Qualifying event stratification was possible in 6796 (97%) pts.

Results
In the overall population, N=6796 (4547 EMPA and 2249 placebo pts), median (Q1, Q3) time from last CV event was 3.8 (1.5–7.6) years. Overall, 1214 (EMPA 841; placebo 373) and 5582 (EMPA 3706; placebo 1876) pts had a last qualifying CV event ≤1 and >1 year, respectively. Pts with more recent events had similar risk for CV outcomes compared with pts >1 year from qualifying event (Figure). Moreover, the benefit of EMPA on CV outcomes was consistent between pts enrolled ≤1 or >1 year from the qualifying CV event (all p-interaction >0.05; Figure).

Conclusion
Although most pts had a qualifying CV event >1 year before randomisation in EMPA-REG OUTCOME, the benefits of EMPA appear to extend to pts with more recent CV events.

Acknowledgement/Funding
Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance
226Earlier surgical myectomy vs. waiting for a Class I indication is associated with improved long-term survival in symptomatic hypertrophic obstructive cardiomyopathy patients
Authors: Alashi A , Smedira N G , Hodges K , Popovic Z B , Thamilarasan M , Wierup P , Lever H M , Desai M Y 
Published: October 2019

Abstract

Background
In patients with severe hypertrophic obstructive cardiomyopathy (HOCM), surgical myectomy (SM) is typically indicated for severe symptoms despite maximal medical therapy.

Aims
We sought to compare long-term outcomes of severe HOCM patients where decision for SM was based on guideline-recommended Class I indication (functional Class or FC ≥3 or exertional syncope despite maximal medical therapy) vs. earlier (FC II and/or impaired exercise capacity on exercise echo with medication intolerance).

Methods
The study included 2268 HOCM patients (excluding <18 years, at least moderate aortic stenosis requiring valve replacement and subaortic membrane, age 56±14 years, 55% men), who underwent SM at our center between 1/02–3/18. Clinical and echo data, including left ventricular outflow tract gradient (LVOTG) were recorded. Cardiac death and/or appropriate internal defibrillator discharge were recorded as composite endpoints.

Results
1318 (58%) patients met Class I indication for SM, while the rest underwent SM for FC II (due to medicine intolerance) or impaired exercise capacity. 535 (24%) and 408 (18%) had history of atrial fibrillation and a family history of HCM. All patients were on maximally tolerated medical therapy. European 5-year sudden death risk score was 3.7±2%. Baseline basal septal thickness, resting and maximal LVOTG were 2.0±0.3 cm, 61±44 mm Hg and 100±31 mm Hg. At 6.2±4 years of follow-up after SM, 248 (11%) had composite events (13 [0.6%] in-hospital deaths). Competing risk survival analysis for composite endpoint is shown in Figure 1a. Patients operated for Class I indication had significantly higher longer-term event rate vs. those operated earlier (182 [14%] vs. 66 [7%], p<0.001, Figure 1B).

Conclusions
In patients with severe HOCM undergoing SM at an experienced center performed by experienced surgeons, delaying surgery till reaching Class I indication was associated with much worse survival than operating earlier for milder symptoms or impaired exercise tolerance on exercise echo.
258Use of low-dose prasugrel vs. clopidogrel in elderly patients undergoing complex or non-complex PCI for acute coronary syndromes: insights from the Elderly ACS 2 study
Authors: Montalto C , Crimi G , Fortuni F , Mandurino Mirizzi A , Piatti L , Morici N , Tortorella G , Grosseto D , Sganzerla P , Ferrario M , De Servi S , Savonitto S 
Published: October 2019

Abstract

Background
Prasugrel was superior to clopidogrel in the setting of acute coronary syndromes (ACS) and recent data highlighted its possible role in the setting of complex percutaneous coronary intervention (PCI). Nonetheless, evidence supporting its use in high bleeding risk population are lacking.

Purpose
The aim of this post-hoc subgroup analysis was to evaluate the impact of prasugrel administration in elderly patients undergoing complex PCI for ACS. A primary composite endpoint of composite of mortality, myocardial infarction, disabling stroke and re-hospitalization for cardiovascular causes or bleeding within one year and secondary endpoints of all-cause mortality and any bleeding at 1 year were analyzed.

Methods
In the multicenter Elderly ACS 2 Study 1,443 patients aged >74 y were randomly assigned to receive low-dose prasugrel (5 mg) or clopidogrel (75 mg) and were prospectively followed for 1 year (Table 1). Complex PCI was defined if ≥3 lesions were treated, if ≥3 stents were deployed, or if any bifurcation, trifurcation, chronic total obstruction or moderate-to-severe calcified lesions were treated.

Results
Patients undergoing complex PCI (n=607) did not experience worse outcome, as compared to those with simpler PCI, in terms of primary endpoint (p=0.21, Figure 1A). Furthermore, in this subgroup, no significant difference was observed with prasugrel vs clopidogrel with regard to the primary endpoint (HR 1.17; CI 0.819–1.67; p=0.39, Figure 1A), all-cause death and bleeding (Figure 1C and 1D). No significant interaction was observed between treatment and PCI complexity (interaction p=0.34).
Table 1 Overall Non-complex PCI Complex PCI p value Age (y) 80.60±4.46 80.00 [77.00, 84.00] 80.00 [77.00, 83.00] 0.215 STE-ACS 595 (41.2) 272 (32.5) 323 (53.4) <0.001 Diabetes mellitus 253 (17.5) 159 (19.0) 94 (15.5) 0.104 LVEF 48.27±9.59 49.08±9.55 47.26±9.54 0.002 Total number of diseased vessels 2.29±1.06 2.22±1.06 2.38±1.05 0.005 Previous Myocardial Infarction 274 (19.0) 171 (20.4) 103 (17.0) 0.122 Randomized to prasugrel 713 (49.4) 404 (48.2) 404 (48.2) 0.307 Data are expressed as mean ± SD or [IQR] and count/valid %).
Figure 1

Conclusions
In elderly patients presenting with ACS low-dose prasugrel was comparable to clopidogrel in terms of all-cause mortality and any bleeding at 1 year.

Acknowledgement/Funding
None
283Endovascular thrombectomy as a means to improve survival in acute ischemic stroke - A meta-analysis
Authors: Lin Y , Schulze V , Brockmeyer M , Parco C , Karathanos A , Krieger T , Heinen Y , Gliem M , Hartung H P , Antoch G , Jander S , Turowski B , Perings S , Kelm M , Wolff G 
Published: October 2019

Abstract

Background and purpose
Although endovascular thrombectomy (EVT) in acute ischemic stroke (AIS) is guideline-recommended to improve functional recovery, thus far there are only inconclusive data from underpowered singular trials of EVT vs. medical therapy (MT) on mortality. We here aimed to perform a meta-analysis on short-term mortality in guideline-relevant EVT vs. MT randomized controlled trials (RCTs).

Methods
All randomized controlled trials (RCT) reporting EVT vs. MT in the latest 2018 American Stroke Association/American Heart Association (ASA/AHA) Guidelines were eligible for inclusion. Data were abstracted by two independent investigators and double-checked by four others. Study data were integrated using the Cochran-Mantel-Haenszel method and a random-effects model to compute summary statistics of risk ratios (RR) with 95% confidence intervals (CI). Ninety-day mortality and intracranial hemorrhage (ICH) were analyzed.

Results
Ten of the twelve guideline-relevant EVT vs. MT RCTs (DAWN, DEFUSE 3, ESCAPE, EXTEND-IA, MR CLEAN, MR RESCUE, REVASCAT, SWIFT PRIME, THERAPY, THRACE) with 2,313 patients were selected for inclusion. Studies IMS III and SYNTHESIS were excluded due to their very infrequent use of EVT. Stent retrievers (Trevo, Solitaire, Merci) were most frequently applied, followed by thrombus aspiration (Penumbra). Intravenous thrombolysis was administered in addition to EVT in the majority of patients. In the pooled meta-analysis of all eligible RCTs, EVT significantly reduced the risk for 90-day mortality by 3.7% compared to MT (15.0% vs. 18.7%; RR 0.81 with CI 0.68 to 0.98; p=0.03), accounting for a number-needed-to-treat of 27 to prevent one all-cause death. Trends were similar in early-window (RR 0.83) and late-window trials only (RR 0.76). There was no difference in the risk for ICH in EVT vs. MT (4.2% vs. 4.0%; RR 1.11 with CI 0.71 to 1.72; p=0.65). All included trials were published in high-quality journals and risk of bias was judged low.

Conclusions
This meta-analysis lends evidence to EVT benefits for survival already during the first 90 days after acute ischemic stroke. These results further highlight the evolution of interventional techniques in this setting.
393Ischemic burden by vasodilator stress CMR predicts long-term all-cause death and the effect of revascularization in patients with known or suspected stable ischemic heart disease
Authors: Marcos Garces V , Gavara J , Rios-Navarro C , Racugno P , Bellver Navarro A , Ventura Perez B , Aguilar Botella J , Ventura S , Mainar L , Bosch M J , Merlos P , Lopez-Lereu M P , Monmeneu J V , Chorro F J , Bodi V 
Published: October 2019

Abstract

Background
In patients with stable ischemic heart disease (SIHD) the effect of revascularization on all-cause death (the most verifiable clinical event) is unknown.

Objectives
We explored the potential of the ischemic burden as derived from vasodilator stress cardiovascular magnetic resonance (CMR) to guide decision-making in this scenario.

Methods
In a large prospective multicenter registry, we recruited 6389 patients (mean age 65±11 years, 38% female) submitted to undergo vasodilator stress CMR for known or suspected SIHD. Baseline and CMR characteristics were prospectively recorded. The ischemic burden (at vasodilator stress first-pass perfusion imaging) and necrosis extent (at late enhancement imaging) were computed (17-segment model). The effect of CMR-related revascularization (within the following three months) on all-cause death (revised using the unified regional electronic health system registry) was explored.

Results
During a 5.75-year median follow-up, 717 (11.2%) all-cause deaths were documented. In multivariable analyses, more extensive ischemic burden (per 1-segment increase) independently related to all-cause death (1.05 [1.03–1.07], p<0.001). In 1034 patients (517 revascularized, 517 non-revascularized) strictly 1:1 matched for the independent predictors of outcome and of undergoing CMR-related revascularization (age, diabetes mellitus, male sex, LVEF, ischemic burden and necrosis extent), CMR-related revascularization did not significantly alter all-cause death rate (13.3% vs. 13.3%, p=0.54). Nevertheless, a potent interaction existed with the ischemic burden (p<0.001). CMR-related revascularization independently reduced the risk of all-cause death in 430 patients with ischemic burden >5 segments (9.3% vs. 16.3%, HR 0.56 [0.32–0.98], p=0.02) but it independently increased risk in 604 patients with ischemic burden ≤5 segments (16.2% vs. 11.3%, HR 1.59 [1.03–2.45], p=0.037).
Figure 1. CMR-related revascularization

Conclusions
In patients with known or suspected stable ischemic heart disease the ischemic burden as derived from vasodilator stress CMR can be helpful to predict the effect of revascularization on long-term all-cause death.

Acknowledgement/Funding
Funded by “Instituto de Salud Carlos III”/FEDER (PIE15/00013, PI17/01836, and CIBERCV16/11/00486 grants) and Generalitat Valenciana (GV/2018/116).