BACKGROUND:Drug-eluting stents (DESs) are recommended treatment for coronary in-stent restenosis (ISR) but are not used in >20% of cases. OBJECTIVES:The aim of the SELUTION4ISR (SELUTION SLR 014 In-stent Restenosis) trial was to assess the safety and effectiveness of a novel sirolimus drug-eluting balloon (DEB). METHODS:After successful lesion predilation, patients with ISR were randomly assigned to the SELUTION Sustained Limus Release (MedAlliance) DEB or a control strategy of usual care, including any approved DES or balloon angioplasty (BA) on the basis of operator selection prerandomization. Randomization to selected BA control treatment was limited to 20% of patients. The primary outcome was target lesion failure (TLF) (cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization) assessed at 1 year in the per protocol group (all treated eligible patients with complete primary endpoint follow-up). Noninferiority was established if the upper limit of the 2-sided 95% credible interval was smaller than 10%. A sequential secondary hypothesis test was performed comparing DEB with DES in patients with single-layer ISR. RESULTS:From July 2020 to July 2024, 418 patients were randomly assigned to the DEB group (n = 210) or the control group (n = 208), with 390 patients per protocol (DEB, 197; control, 193 [154 DES; 39 BA]). TLF occurred in 32 (16.2%) of 197 patients in the DEB group and in 28 (14.5%) of 193 patients in the control group (difference: 1.7%; 95% credible interval: -5.5% to 8.9%; posterior probability of noninferiority: 98.80%). In the secondary hypothesis test, TLF occurred in 22 (14.2%) of 155 patients in the DEB group and in 9 (6.5%) of 138 patients in the DES control group (difference: 7.7%; 95% credible interval: 0.6%-14.6%, posterior probability for noninferiority: 76.07%). TLF according to operator selected control was higher for DEB compared with DES (15.3% vs 7.1%; difference: 8.1%; 95% credible interval: 1.4%-15.0%) and lower for DEB compared with BA (23.6% vs 43.6%; difference: 23.7%; 95% credible interval: -41.4% to -1.5%; Pforinteraction = 0.0026). CONCLUSIONS:The sirolimus DEB was noninferior to a usual care control strategy including 80% repeat DES but not noninferior to DES for single-layer ISR for TLF at 12 months. There was significant interaction on the basis of operator selection of DES vs BA. (SELUTION SLR 014 In-stent Restenosis [SELUTION4ISR]; NCT04280029).
AIMS:We aimed to develop the European Society of Cardiology (ESC) quality indicators (QIs) for myocardial infarction (MI), from 1 year after hospital discharge, corresponding to transition to the chronic coronary syndrome phases. METHODS AND RESULTS:We collaborated with the European Association of Preventive Cardiology (EAPC) and developed QIs for the long-term management of patients following MI. We applied the ESC methodology for QI development by (i) determining key domains of post-MI care; (ii) developing candidate QIs by performing a systematic review of the literature, and (iii) selecting the final set of QIs using a modified Delphi approach. In total, 18 QIs were identified across seven domains of care including (i) structural framework, (ii) risk assessment and follow-up, (iii) pharmacological management, (iv) rehabilitation, behavioural, and preventive interventions, (v) coronary revascularization, (vi) clinical outcomes, and (vii) patient-reported outcomes. CONCLUSION:We present the ESC QIs from 1 year after hospitalization for MI, to standardize and address gaps in care for this high-risk group. These QIs are supported by evidence from contemporary literature, endorsed by expert consensus, and aligned with the 2024 ESC guidelines on the management of chronic coronary syndromes. LAY SUMMARY:Measures to evaluate and improve the long-term management of patients following a heart attack are needed. In this paper, we identified key aspects of care that can help clinicians, decision-makers and patients improve the quality of care, from one year after a heart attack onwards, and help address inequalities and variations in clinical practice.
Outcome prediction after traumatic spinal cord injury (SCI) remains challenging due to patient heterogeneity, highlighting the need for better prognostic tools. Neural tissue damage and blood-spinal cord barrier disruption expose the immune system to spinal cord proteins, eliciting autoantibody responses that may be beneficial or detrimental. This study aimed to identify the (auto)antibody profile of SCI patients, and examine the prognostic antibody biomarker potential. A healthy and a SCI cDNA phage display library were screened for novel antibodies using SCI samples (n = 12/11). Antibody reactivity was validated using phage ELISA in 291 samples from 190 SCI patients collected at baseline (0-4 days post-injury [dpi]) and follow-up (15-30 dpi; 31-56 dpi). Correlations between antibody reactivity and clinical characteristics including SCI level, and American Spinal Injury Association impairment scale (AIS), were analysed. Immunofluorescent stainings were used to validate expression of two antigenic targets. We identified antibodies against 6 novel autoantigens (University Hasselt [UH.] SCI.104/105/106/108/109/110). A panel of three antigens (UH.SCI.104/109/110) demonstrated increased antibody reactivity in 31.3% of SCI patients with AIS improvement versus 4.8% with no improvement, resulting in a positive likelihood ratio of 6.56. Patients with injuries above thoracic level 4 had significantly lower antibody reactivity against UH.SCI.105/110 compared to patients with lower lesions. Anti-UH.SCI.108/110 antibodies bound to astrocytes, in mouse spinal cord tissue and primary cell cultures, confirming disease-relevant reactivity. Antibodies targeting the novel antigens demonstrated prognostic biomarker potential, supporting their future use in outcome prediction and patient stratification for SCI management and clinical trial design.
Exercise intolerance is a clinical hallmark of heart failure with preserved ejection fraction (HFpEF) that confers high morbidity and predicts mortality. The mechanisms underlying exercise intolerance in HFpEF are diverse and often include compound deficits in multi-organ reserve capacity that culminate in marked functional limitations. This review describes aetiologies of exercise intolerance in HFpEF, tools to quantify relative physiologic deficits unmasked during exercise, and insights gained from interventional trials that have aimed to augment exercise capacity in HFpEF. The domain-based phenotyping approach described highlights the value of comprehensive phenotyping of both cardiac and extra-cardiac reserve capacity to advance understanding of how to deploy individualized interventions to bolster exercise tolerance in HFpEF.
