Abstract
Background
Spontaneous coronary artery dissection (SCAD) is an increasingly diagnosed cause of myocardial infarction. Although different SCAD angiographic classifications exist, their ...clinical impact remains unknown.
Purpose
To evaluate the relationship between an angiographic classification and the development of adverse clinical events during the follow-up of a large, unselected cohort of patients with SCAD.
Methods
We conducted an observational study of consecutive SCAD patients from 26 centers across Italy and Spain. Cases were classified into 5 different angiotypes according to the latest classification endorsed by the European Society of Cardiology. The main composite endpoint included all-cause death, non-fatal myocardial infarction (MI), and any unplanned revascularisation.
Results
In total, 302 SCAD patients (mean age 51.8±19 years) were followed up for a median of 22 months (IQR 12–48). At 28 days, the composite outcome was higher for the angiotypes with a circumscribed contained intramural hematoma (2A and 3): 20.0% vs. 5.4%, p<0.001 (non-fatal MI: 11.0% vs. 3.5%, p=0.009; unplanned revascularisation: 11.0% vs. 2.5%, p<0.001), which was sustained during follow-up (24.5% vs. 9.9%, p=0.001). There were no differences in mortality (0,3% overall). The presence of an angiotype 2A or 3 was an independent predictor of a higher incidence of the composite outcome (adjusted HR: 2.44, CI 1.24–4.80, p=0.010).
Conclusions
The SCAD angiographic classification correlates with outcome. Those presenting with an angiographically circumscribed contained intramural hematoma (angiotypes 2A and 3) showed an increased risk of short-term adverse clinical events that was maintained during follow-up.
Funding Acknowledgement
Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Society of Cardiology KM curves for angiotypes 2A & 3 vs otherKM curves for angiotypes 2A & 3 vs other
Abstract
Aims
The role of antiplatelet therapy in patients with spontaneous coronary artery dissection (SCAD) undergoing initial conservative management is still a matter of debate, with theoretical ...arguments in favour and against its use. The aims of this article are to assess the use of antiplatelet drugs in medically treated SCAD patients and to investigate the relationship between single (SAPT) and dual (DAPT) antiplatelet regimens and 1-year patient outcomes.
Methods and results
We investigated the 1-year outcome of patients with SCAD managed with initial conservative treatment included in the DIssezioni Spontanee COronariche (DISCO) multicentre international registry. Patients were divided into two groups according to SAPT or DAPT prescription. Primary endpoint was 12-month incidence of major adverse cardiovascular events (MACE) defined as the composite of all-cause death, non-fatal myocardial infarction (MI), and any unplanned percutaneous coronary intervention (PCI). Out of 314 patients included in the DISCO registry, we investigated 199 patients in whom SCAD was managed conservatively. Most patients were female (89%), presented with acute coronary syndrome (92%) and mean age was 52.3 ± 9.3 years. Sixty-seven (33.7%) were given SAPT whereas 132 (66.3%) with DAPT. Aspirin plus either clopidogrel or ticagrelor were prescribed in 62.9% and 36.4% of DAPT patients, respectively. Overall, a 14.6% MACE rate was observed at 12 months of follow-up. Patients treated with DAPT had a significantly higher MACE rate than those with SAPT 18.9% vs. 6.0% hazard ratios (HR) 2.62; 95% confidence intervals (CI) 1.22–5.61; P = 0.013, driven by an early excess of non-fatal MI or unplanned PCI. At multiple regression analysis, type 2a SCAD (OR: 3.69; 95% CI 1.41–9.61; P = 0.007) and DAPT regimen (OR: 4.54; 95% CI 1.31–14.28; P = 0.016) resulted independently associated with a higher risk of 12-month MACE.
Conclusions
In this European registry, most patients with SCAD undergoing initial conservative management received DAPT. Yet, at 1-year follow-up, DAPT, as compared with SAPT, was independently associated with a higher rate of adverse cardiovascular events (ClinicalTrial.gov id: NCT04415762).
The optimal management of patients with spontaneous coronary artery dissection remains debated.
Patients enrolled in the DISCO (Dissezioni Spontanee Coronariche) Registry up to December 2020 were ...included. The primary end point was major adverse cardiovascular events, a composite of all-cause death, nonfatal myocardial infarction, and repeat percutaneous coronary intervention (PCI). Independent predictors of PCI and medical management were investigated.
Among 369 patients, 129 (35%) underwent PCI, whereas 240 (65%) were medically managed. ST-segment-elevation myocardial infarction (68% versus 35%,
<0.001), resuscitated cardiac arrest (9% versus 3%,
<0.001), proximal coronary segment involvement (32% versus 7%,
<0.001), and Thrombolysis in Myocardial Infarction flow 0 to 1 (54% versus 20%,
<0.001) were more frequent in the PCI arm. In-hospital event rates were similar. Between patients treated with PCI and medical therapy, there were no differences in terms of major adverse cardiovascular events at 2 years (13.9% versus 11.7%,
=0.467), all-cause death (0.7% versus 0.4%,
=0.652), myocardial infarction (9.3% versus 8.3%,
=0.921) and repeat PCI (12.4% versus 8.7%,
=0.229). ST-segment-elevation myocardial infarction at presentation (odds ratio OR, 3.30 95% CI, 1.56-7.12;
=0.002), proximal coronary segment involvement (OR, 5.43 95% CI, 1.98-16.45;
=0.002), Thrombolysis in Myocardial Infarction flow grade 0 to 1 and 2 (respectively, OR, 3.22 95% CI, 1.08-9.96;
=0.038; and OR, 3.98 95% CI, 1.38-11.80;
=0.009) and luminal narrowing (OR per 5% increase, 1.13 95% CI, 1.01-1.28;
=0.037) were predictors of PCI, whereas the 2B-angiographic subtype predicted medical management (OR, 0.25 95% CI, 0.07-0.83;
=0.026).
Clinical presentation and procedural variables drive the choice of the initial therapeutic approach in spontaneous coronary artery dissection. If PCI is needed, it seems to be associated with a similar risk of short-to-mid-term adverse events compared to medical treatment.
URL: https://www.
gov; Unique identifier: NCT04415762.
Information about the impact of cancer treatments on patients' quality of life (QoL) is of paramount importance to patients and treating oncologists. Cancer trials that do not specify QoL as an ...outcome or fail to report collected QoL data, omit crucial information for decision making. To estimate the magnitude of these problems, we investigated how frequently QoL outcomes were specified in protocols of cancer trials and subsequently reported.
Retrospective cohort study of RCT protocols approved by six research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We compared protocols to corresponding publications, which were identified through literature searches and investigator surveys.
Of the 173 cancer trials, 90 (52%) specified QoL outcomes in their protocol, 2 (1%) as primary and 88 (51%) as secondary outcome. Of the 173 trials, 35 (20%) reported QoL outcomes in a corresponding publication (4 modified from the protocol), 18 (10%) were published but failed to report QoL outcomes in the primary or a secondary publication, and 37 (21%) were not published at all. Of the 83 (48%) trials that did not specify QoL outcomes in their protocol, none subsequently reported QoL outcomes. Failure to report pre-specified QoL outcomes was not associated with industry sponsorship (versus non-industry), sample size, and multicentre (versus single centre) status but possibly with trial discontinuation.
About half of cancer trials specified QoL outcomes in their protocols. However, only 20% reported any QoL data in associated publications. Highly relevant information for decision making is often unavailable to patients, oncologists, and health policymakers.
Objective To investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications. Design Cohort of protocols of ...randomised controlled trial and subsequent full journal publications. Setting Six research ethics committees in Switzerland, Germany, and Canada. Data sources 894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications. Results Of 894 protocols of randomised controlled trials, 252 (28.2%) included one or more planned subgroup analyses. Of those, 17 (6.7%) provided a clear hypothesis for at least one subgroup analysis, 10 (4.0%) anticipated the direction of a subgroup effect, and 87 (34.5%) planned a statistical test for interaction. Industry sponsored trials more often planned subgroup analyses compared with investigator sponsored trials (195/551 (35.4%) v 57/343 (16.6%), P<0.001). Of 515 identified journal publications, 246 (47.8%) reported at least one subgroup analysis. In 81 (32.9%) of the 246 publications reporting subgroup analyses, authors stated that subgroup analyses were prespecified, but this was not supported by 28 (34.6%) corresponding protocols. In 86 publications, authors claimed a subgroup effect, but only 36 (41.9%) corresponding protocols reported a planned subgroup analysis. Conclusions Subgroup analyses are insufficiently described in the protocols of randomised controlled trials submitted to research ethics committees, and investigators rarely specify the anticipated direction of subgroup effects. More than one third of statements in publications of randomised controlled trials about subgroup prespecification had no documentation in the corresponding protocols. Definitive judgments regarding credibility of claimed subgroup effects are not possible without access to protocols and analysis plans of randomised controlled trials.
Abstract only
Introduction:
Spontaneous coronary artery dissection (SCAD) is an understudied cause of acute myocardial infarction due to hematoma formation in coronary arteries primarily affecting ...women. It is not known to what extent SCAD is genetically distinct from other cardiovascular diseases, including atherosclerotic coronary artery disease (CAD).
Methods and Results:
Through a meta-analysis of 8 GWAS (1917 cases, 9292 controls of European ancestry), we identified 17 risk loci, including 12 new. Functional annotations pointed at enrichment in enhancer marks of arteries, specifically smooth muscle cells, and strong candidate genes, such as tissue factor gene (
F3
) on Chr1 near rs1146473 (OR=1.32, P=5.8 х10
-9
).
F3
is novel for SCAD or any cardiovascular disease. The risk allele correlated with
F3
lower expression in arteries, supporting a mechanism consistent with hematoma formation. Bayesian gene regulatory networks constructed from expression and genetics data indicated the extracellular matrix organization in arteries as the biological function where most prioritized genes clustered (e.g.
COL4A1/A2, HTRA1,
and
TIMP3
). Overall, we report substantial polygenicity for SCAD (LDSC:
h
2
SNP
=
0.71 ± 0.11) and shared genetics with several neurovascular diseases (e.g intracranial aneurysm). Intriguingly, for 6 loci, colocalization analyses showed that SCAD and CAD are likely to share the same causal variants but involve opposite risk alleles (e.g
COL4A1/A2
). In addition, a negative genetic correlation was found between SCAD and CAD (rg=-0.12; P=3.7х10
-3
), including after conditioning on BP (mt-COJO: rg
CAD/SBP
=-0.19, P=4.6х10
-6
). Mendelian randomization analyses indicated higher BP to associate with increased risk for SCAD (beta
IVW-SBP
=0.05, P=7.6х10
-6
, beta
IVW-DBP
=0.10, P=1.9х10
-6
) and CAD (beta
IVW-SBP
=0.04, P=8.6х10
-49
; DBP: beta
IVW-DBP
=0.06, P=1.6х10
-44
) but not BMI, lipids, or type 2 diabetes, which we confirmed as genetic risk factors for CAD
Conclusions:
Our results set the stage for future investigation of novel biological pathways relevant to both SCAD and CAD and potential therapeutic and preventive strategies specifically targeting this ischemic disease predominantly affecting women.
Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have ...reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene.
This study sought to test the association between the rs9349379 genotype and SCAD.
Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD.
The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval CI: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence.
The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD.
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With the recent advance in genome-wide association studies (GWAS), disease-associated single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) have been extensively reported. ...Accordingly, the issue of incorrect identification of recombination events that can induce the distortion of multi-allelic or hemizygous variants has received more attention. However, the potential distorted calculation bias or significance of a detected association in a GWAS due to the coexistence of CNVs and SNPs in the same genomic region may remain under-recognized. Here we performed the association study within a congenital scoliosis (CS) cohort whose genetic etiology was recently elucidated as a compound inheritance model, including mostly one rare variant deletion CNV null allele and one common variant non-coding hypomorphic haplotype of the
TBX6
gene. We demonstrated that the existence of a deletion in
TBX6
led to an overestimation of the contribution of the SNPs on the hypomorphic allele. Furthermore, we generalized a model to explain the calculation bias, or distorted significance calculation for an association study, that can be ‘induced’ by CNVs at a locus. Meanwhile, overlapping between the disease-associated SNPs from published GWAS and common CNVs (overlap 10%) and pathogenic/likely pathogenic CNVs (overlap 99.69%) was significantly higher than the random distribution (
p
< 1 × 10
−6
and
p
= 0.034, respectively), indicating that such co-existence of CNV and SNV alleles might generally influence data interpretation and potential outcomes of a GWAS. We also verified and assessed the influence of colocalizing CNVs to the detection sensitivity of disease-associated SNP variant alleles in another adolescent idiopathic scoliosis (AIS) genome-wide association study. We proposed that detecting co-existent CNVs when evaluating the association signals between SNPs and disease traits could improve genetic model analyses and better integrate GWAS with robust Mendelian principles.
Premature discontinuation of clinical studies affects about 25% of randomised controlled trials (RCTs) which raises concerns about waste of scarce resources for research. The risk of discontinuation ...of non-randomised prospective studies (NPSs) is yet unclear.
To compare the proportion of discontinued studies between NPSs and RCTs that received ethical approval.
We systematically surveyed prospective longitudinal clinical studies that were approved by a single REC in Freiburg, Germany between 2000 and 2002. We collected study characteristics, identified subsequent publications, and surveyed investigators to elucidate whether a study was discontinued and, if so, why.
Of 917 approved studies, 547 were prospective longitudinal studies (306 RCTs and 241 NPSs). NPSs were on average smaller than RCTs, more frequently single centre and pilot studies, and less frequently funded by industry. NPSs were less frequently discontinued than RCTs: 32/221 (14%) versus 78/288 (27%, p<0.001, missing data excluded). Poor recruitment was the most frequent reason for discontinuation in both NPSs (36%) and RCTs (37%).
Compared to RCTs, NPSs were at lower risk for discontinuation. Measures to reliably predict, sustain, and stimulate recruitment could prevent discontinuation of many RCTs but also of some NPSs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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