Abstract
Identification and management of patients at high bleeding risk undergoing percutaneous
coronary intervention are of major importance, but a lack of standardization in defining
this ...population limits trial design, data interpretation, and clinical decision-making.
The Academic Research Consortium for High Bleeding Risk (ARC-HBR) is a collaboration among
leading research organizations, regulatory authorities, and physician-scientists from the
United States, Asia, and Europe focusing on percutaneous coronary intervention–related
bleeding. Two meetings of the 31-member consortium were held in Washington, DC, in April
2018 and in Paris, France, in October 2018. These meetings were organized by the
Cardiovascular European Research Center on behalf of the ARC-HBR group and included
representatives of the US Food and Drug Administration and the Japanese Pharmaceuticals
and Medical Devices Agency, as well as observers from the pharmaceutical and medical
device industries. A consensus definition of patients at high bleeding risk was developed
that was based on review of the available evidence. The definition is intended to provide
consistency in defining this population for clinical trials and to complement clinical
decision-making and regulatory review. The proposed ARC-HBR consensus document represents
the first pragmatic approach to a consistent definition of high bleeding risk in clinical
trials evaluating the safety and effectiveness of devices and drug regimens for patients
undergoing percutaneous coronary intervention.
Restenosis remains the major limitation of coronary catheter-based intervention. In small vessels, the amount of neointimal tissue is disproportionately greater than the vessel caliber, resulting in ...higher restenosis rates. In the Randomized Study With the Sirolimus-Eluting Bx Velocity Balloon-Expandable Stent (RAVEL) trial, approximately 40% of the vessels were small (<2.5 mm). The present study evaluates the relationship between angiographic outcome and vessel diameter for sirolimus-eluting stents.
Patients were randomized to receive either an 18-mm bare metal Bx VELOCITY (BS group, n=118), or a sirolimus-eluting Bx VELOCITY stent (SES group, n=120). Subgroups were stratified into tertiles according to their reference diameter (RD; stratum I, RD <2.36 mm; stratum II, RD 2.36 mm to 2.84 mm; stratum III, RD >2.84 mm). At 6-month follow-up, the restenosis rate in the SES group was 0% in all strata (versus 35%, 26%, and 20%, respectively, in the BS group). In-stent late loss was 0.01+/-0.25 versus 0.80+/-0.43 mm in stratum I, 0.01+/-0.38 versus 0.88+/-0.57 mm in stratum II, and -0.06+/-0.35 versus 0.74+/-0.57 mm in stratum III (SES versus BS). In SES, the minimal lumen diameter (MLD) remained unchanged (Delta -0.72 to 0.72 mm) in 97% of the lesions and increased (=late gain, DeltaMLD <-0.72 mm) in 3% of the lesions. Multivariate predictors for late loss were treatment allocation (P<0.001) and postprocedural MLD (P= 0.008).
Sirolimus-eluting stents prevent neointimal proliferation and late lumen loss irrespective of the vessel diameter. The classic inverse relationship between vessel diameter and restenosis rate was seen in the bare stent group but not in the sirolimus-eluting stent group.
The prognostic implications of periprocedural myocardial infarction (PMI) after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) remain controversial. We examined ...the 3-year rates of mortality among patients with and without PMI undergoing left main coronary artery intervention randomized to PCI with everolimus-eluting stents vs. CABG in the large-scale, multicentre, prospective, randomized EXCEL trial.
By protocol, PMI was defined using an identical threshold for PCI and CABG creatinine kinase-MB (CK-MB) elevation >10× the upper reference limit (URL) within 72 h post-procedure, or >5× URL with new Q-waves, angiographic vessel occlusion, or loss of myocardium on imaging. Cox proportional hazards modelling was performed controlling for age, sex, hypertension, diabetes mellitus, left ventricular ejection fraction, SYNTAX score, and chronic obstructive pulmonary disease (COPD). A total of 1858 patients were treated as assigned by randomization. Periprocedural MI occurred in 34/935 (3.6%) of patients in the PCI group and 56/923 (6.1%) of patients in the CABG group odds ratio 0.61, 95% confidence interval (CI) 0.40-0.93; P = 0.02. Periprocedural MI was associated with SYNTAX score, COPD, cross-clamp duration and total procedure duration, and not using antegrade cardioplegia. By multivariable analysis, PMI was associated with cardiovascular death and all-cause death at 3 years adjusted hazard ratio (HR) 2.63, 95% CI 1.19-5.81; P = 0.02 and adjusted HR 2.28, 95% CI 1.22-4.29; P = 0.01, respectively. The effect of PMI was consistent for PCI and CABG for cardiovascular death (Pinteraction = 0.56) and all-cause death (Pinteraction = 0.59). Peak post-procedure CK-MB ≥10× URL strongly predicted mortality, whereas lesser degrees of myonecrosis were not associated with prognosis.
In the EXCEL trial, PMI was more common after CABG than PCI, and was strongly associated with increased 3-year mortality after controlling for potential confounders. Only extensive myonecrosis (CK-MB ≥10× URL) was prognostically important.
Objectives
We examined outcomes according to lesion preparation strategy (LPS) in patients with left main coronary artery (LMCA) percutaneous coronary intervention (PCI) in the EXCEL trial.
...Background
The optimal LPS for LMCA PCI is unclear.
Methods
We categorized LPS hierarchically (high to low) as: (a) rotational atherectomy (RA); (b) cutting or scoring balloon (CSB); (c) balloon angioplasty (BAL); and d) direct stenting (DIR). The primary endpoint was 3‐year MACE; all‐cause death, stroke, or myocardial infarction.
Results
Among 938 patients undergoing LMCA PCI, RA was performed in 6.0%, CSB 9.5%, BAL 71.3%, and DIR 13.2%. In patients treated with DIR, BAL, CSB, and RA, respectively, there was a progressive increase in SYNTAX score, LMCA complex bifurcation, trifurcation or calcification, number of stents, and total stent length. Any procedural complication occurred in 10.4% of cases overall, with the lowest rate in the DIR (7.4%) and highest in the RA group (16.1%) (ptrend = .22). There were no significant differences in the 3‐year rates of MACE (from RA to DIR: 17.9%, 20.2%, 14.5%, 14.7%; p = .50) or ischemia‐driven revascularization (from RA to DIR: 16.8%, 10.8%, 12.3%, 14.2%; p = .65). The adjusted 3‐year rates of MACE did not differ according to LPS.
Conclusions
The comparable 3‐year outcomes suggest that appropriate lesion preparation may be able to overcome the increased risks of complex LMCA lesion morphology.
Objectives
To evaluate the impact of coronary artery disease (CAD) with or without recent (≤ 30 days) percutaneous coronary intervention (PCI) in women undergoing transcatheter aortic valve ...replacement (TAVR).
Background
Although women display a specific risk‐profile for both PCI and TAVR, the impact of CAD and PCI in the setting of TAVR in women is unclear.
Methods
The multinational Women's International Transcatheter Aortic Valve implantation registry enrolled consecutive female patients undergoing contemporary TAVR in 19 centers between 2013 and 2015. Patients with available coronary angiography or CT scan in the pre‐operative assessment of TAVR were categorized as without CAD, with CAD but no recent PCI and CAD and recent PCI (≤30 days). All events were adjudicated according to the VARC‐2 criteria.
Results
A total of 787 patients were included in this analysis, among whom 459 (58.3%) had no CAD, 247 (31.4%) had CAD without recent PCI and 81 (10.3%) underwent recent PCI (≤ 30 days before TAVR). After multivariable adjustment, both groups of CAD patients, without and with recent PCI, presented with higher risk of death, myocardial infarction or stroke, compared with patients without CAD (adjHR 1.56, 95%CI 1.03–2.39, P = 0.038 and adjHR 1.96, 95% CI 1.1–3.5, P = .021, respectively). Patients with recent PCI had increased risk of all‐cause death (adjHR 1.89, 95% CI 1.0–3.5, P = 0.04) and stroke (adjHR 3.7, 95% CI 1.0–13.5, P = 0.046) compared with patients without CAD.
Conclusion
The presence of CAD in women undergoing TAVR, with or without recent PCI, was associated with long‐term poorer outcomes.
The diagnostic accuracy of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the diagnosis of lymphoma in patients with mediastinal lymphadenopathy is not well defined.
...A retrospective review was performed of all patients with mediastinal lymphadenopathy referred for EBUS-TBNA between August 2005 and December 2006 in whom lymphoma was suspected based on prior history or clinical presentation. Mediastinal biopsy specimens were taken using a linear array ultrasonic bronchoscope (Olympus XBF-UC 160F) and a 22-gauge cytology needle (NA-202C Olympus) with on-site cytopathological support. The EBUS-TBNA result was compared with a reference standard of pathological tissue diagnosis or a composite of > or =6 months of clinical follow-up with radiographic imaging.
Of 236 patients who underwent EBUS-TBNA, 25 were eligible for inclusion. Indications for EBUS-TBNA were suspected mediastinal recurrence of lymphoma (n = 13) and mediastinal lymphadenopathy of unknown cause (n = 12). Adequate lymph node sampling was accomplished in 24/25 patients (96%); there were no complications. EBUS-TBNA identified lymphoma in 10 patients and benign disease in 14 patients. There was one false negative EBUS-TBNA for lymphoma (lymphoma prevalence 11/25 (44%)). Follow-up over a median of 10.5 months (range 1-19) confirmed stable or regressive lymphadenopathy in all 14 patients without a lymphoma diagnosis, consistent with a benign diagnosis. Overall, EBUS-TBNA had a sensitivity of 90.9%, specificity of 100%, positive predictive value of 100% and negative predictive value of 92.9% for the diagnosis of lymphoma.
EBUS-TBNA is an accurate, safe and useful tool in the investigation of suspected lymphoma with isolated mediastinal adenopathy, and may diminish the need for more invasive procedures such as mediastinoscopy.
Summary
Background
Data on dermatological manifestations of Noonan syndrome (NS) remain heterogeneous and are based on limited dermatological expertise.
Objectives
To describe the dermatological ...manifestations of NS, compare them with the literature findings, and test for dermatological phenotype–genotype correlations with or without the presence of PTPN11 mutations.
Methods
We performed a large 4‐year, prospective, multicentric, collaborative dermatological and genetic study.
Results
Overall, 129 patients with NS were enrolled, including 65 patients with PTPN11‐NS, 34 patients with PTPN11‐NS with multiple lentigines (NSML), and 30 patients with NS who had a mutation other than PTPN11. Easy bruising was the most frequent dermatological finding in PTPN11‐NS, present in 53·8% of patients. Multiple lentigines and café‐au‐lait macules (n ≥ 3) were present in 94% and 80% of cases of NSML linked to specific mutations of PTPN11, respectively. Atypical forms of NSML could be associated with NS with RAF1 or NRAS mutations. In univariate analysis, patients without a PTPN11 mutation showed (i) a significantly higher frequency of keratinization disorders (P = 0·001), including keratosis pilaris (P = 0·005), ulerythema ophryogenes (P = 0·0001) and palmar and/or plantar hyperkeratosis (P = 0·06, trend association), and (ii) a significantly higher frequency of scarce scalp hair (P = 0·035) and scarce or absent eyelashes (P = 0·06, trend association) than those with PTPN11 mutations.
Conclusions
The cutaneous phenotype of NS with a PTPN11 mutation is generally mild and nonspecific, whereas the absence of a PTPN11 mutation is associated with a high frequency of keratinization disorders and hair abnormalities.
What's already known about this topic?
Data on dermatological manifestations of Noonan syndrome (NS) remain heterogeneous and almost entirely without expert dermatological input.
A broad spectrum of dermatological findings is present in NS and better knowledge might help to define phenotype–genotype correlations and differentiate forms of NS from other RASopathies, specifically cardiofaciocutaneous syndrome.
What does this study add?
NS with PTPN11 mutations is usually associated with a mild and nonspecific cutaneous phenotype.
NS with multiple lentigines is typically associated with specific mutations of PTPN11 but atypical forms can be linked to RAF1 or NRAS mutations.
Absence of PTPN11 mutation in NS is associated with a higher frequency of keratinization disorders and hair abnormalities, the latter being commonly observed in cardiofaciocutaneous syndrome.
What is the translational message?
Abnormalities of the genes of the Ras–MAPK signalling pathway that are involved in NS underlie a spectrum of cutaneous manifestations including hair abnormalities, keratinization, pigmentary and connective tissue disorders and multiple melanocytic naevi.
This study adds new information to improve the definition of the cutaneous phenotype of NS and differentiate it phenotypically from RASopathies, specifically cardiofaciocutaneous syndrome and Costello syndrome.
Linked Comment: Carcavilla. Br J Dermatol 2019; 180:1293.
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