Kris Bogaerts

BACKGROUND: Implantation of drug eluting stents (DESs) is currently the default approach for percutaneous coronary interventions, but long-term adverse events still exist. An approach with minimal stenting deserves to be assessed in a randomized trial. We studied a novel sirolimus-eluting balloon (SEB) that elutes sirolimus over a 90-day period using a biodegradable polymer microreservoir technology. METHODS: In a multicenter, open-label, randomized trial, we compared an SEB-based strategy with provisional DES with one of systematic DES for de novo lesions in coronary arteries between 2 and 5 mm in diameter. Subjects were randomized 1:1 before percutaneous coronary intervention. The primary end point was target vessel failure, a composite of cardiac death, target vessel–related myocardial infarction, and clinically driven target vessel revascularization. It was tested for noninferiority at 1 year with the use of an absolute margin equal to 50% of the combined event rate at a significance level of 0.025. The primary analysis population included all randomized subjects with completed or attempted percutaneous revascularization, analyzed according to the intention-to-treat principle. A sensitivity analysis was performed on the per-protocol population. RESULTS: Between August 27, 2021, and July 29, 2024, 3323 participants were randomized and treated in 62 sites. Among 1661 participants in the SEB strategy group, bailout stenting was performed in 343 (20.7%). Target vessel failure occurred over 365 days in 88 (5.3%) and 73 (4.4%) participants in the SEB and the systematic DES strategy groups, respectively (risk difference, 0.91% [95% CI –0.55% to 2.38%]; 1-sided P =0.02 for noninferiority with a 2.44% noninferiority margin). Clinically driven target vessel revascularization occurred more frequently in the SEB strategy group (3.3% versus 2.1%; risk difference, 1.22% [95% CI, 0.11%–2.33%). Safety events, including lesion thrombosis, were low and similar in both groups. Although the results of the per-protocol population (3194 participants, 96%) did not confirm noninferiority (upper boundary of the 95% CI, 2.63; P =0.04), they were similar to the intention-to-treat results in both magnitude and direction. CONCLUSIONS: At 1 year, in the primary intention-to-treat analysis population, a strategy of percutaneous coronary intervention with SEB and provisional DES was noninferior to the systematic use of DES for the primary end point of target vessel failure. The per-protocol population sensitivity analysis did not confirm noninferiority. Clinically driven target vessel revascularization occurred more frequently in the SEB strategy group. At 5 years, target vessel failure will be tested again for noninferiority and for superiority if noninferiority is achieved. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04859985.

Aims: The natural history and response to tafamidis treatment in women with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) remain insufficiently characterized. Current study aimed to explore sex-differences in clinical presentation, natural course, and tafamidis treatment efficacy, focusing on women with ATTRwt-CM. Methods and results: An international, multicentric cohort of ATTRwt-CM subjects was evaluated, including for all-cause mortality. In total, 1454 patients were studied (mean age 81 ± 7y), including 307 (21.1%) females. At presentation, females were ∼3 years older than males with slightly worse phenotype, including higher indexed left ventricular wall thickness and National Amyloidosis Centre (NAC) disease stage (P < 0.050). Heart failure with preserved ejection fraction and hypertension coincided more often in women (P = 0.001). Natural disease course was poor without sex-difference, even when age-corrected (P = 0.210). Tafamidis was initiated in 1055 patients, 12% less in females (P < 0.001), although reasons for non-initiation and discontinuation did not show heterogeneity by sex (P = 0.116 and P = 0.304, respectively), indicating structural undertreatment. After 1.9 (0.9–3.3) years of median follow-up, 409 (28.1%) patients died. Tafamidis related to lower mortality in the overall and propensity score-matched cohort (n = 742, HR 0.44, 95% CI 0.32–0.61, P < 0.001), without sex-difference (female HR 0.76, 95% CI 0.52–1.11, P = 0.150) nor sex-based treatment efficacy interaction (P = 0.381). NAC disease stages strongly related to mortality under tafamidis treatment (HR 2.13%, 95%, 1.81–2.50, P < 0.001), but female sex did not (HR 0.82, 95% CI 0.53–1.27, P = 0.365). Conclusion: Women with ATTRwt-CM are prone to underdiagnosis and undertreatment, despite similar poor natural course and tafamidis treatment efficacy. Initiatives to increase diagnostic awareness and disease modifying treatment initiation in women are urgently needed.

Aims: Contemporary guidelines support the use of a pharmaco-invasive (PI) strategy with immediate transfer to a percutaneous coronary intervention (PCI)-capable hospital for ST-elevation myocardial infarction when a timely primary PCI (pPCI) is unattainable. However, when reperfusion with fibrinolysis fails to occur, rescue PCI is recommended. Methods and results: In a pre-specified analysis from STREAM-2, we explored patients randomized to PI treatment and compared those receiving half-dose tenecteplase and required rescue intervention to those with successful fibrinolysis undergoing scheduled angiography. To provide context for those randomized to pPCI, we also explored the relationship between sites of randomization, i.e. community hospital (CH) vs. ambulance on clinical outcomes. Resolution of ST-elevation following angiography and the composite of 30-day all-cause death, shock, heart failure, and reinfarction, as well as safety, reflected by stroke and non-intracranial bleeding, were measured. Of the 583 patients in the current study, 168 patients required rescue intervention (43.5%), 218 patients had successful fibrinolysis scheduled for angiography, and 197 were randomized to pPCI. Rescue PCI patients, compared with those undergoing scheduled angiography, had less ST resolution ≥50% (76.3 vs. 92.5%, P < 0.001) and worse clinical composite outcomes at 30 days (16.7 vs. 6.0%, P < 0.001) with a higher risk of intracranial haemorrhage (2.4 vs. 0.5%). Intermediate outcomes were observed for patients undergoing pPCI (ST resolution ≥50%: 78.7%; a 30-day composite outcome: 12.2%). Rescue intervention deployed in CH patients required 10 min longer compared with ambulance patients; however, there was a similar ST resolution of ≥50% (72.2 vs. 80.5%, P = 0.219) and comparable 30-day composite outcomes [17.6 vs. 15.7%, relative risk (RR) 0.97, 95% confidence interval (CI) 0.50–1.87], irrespective of location. Primary PCI required 48 min longer in CH patients, but resulted in similar outcomes to ambulance patients (ST resolution ≥50%: 77.0 vs. 80.2%, P = 0.595; 30-day composite outcome: 9.3 vs. 15.6%, RR 1.57, 95% CI 0.72–3.41, respectively). Conclusion: Contemporary PI with half-dose tenecteplase in older patients requiring rescue intervention led to less ST resolution and worse 30-day outcomes compared with those with successful fibrinolysis receiving scheduled angiography. Notably, delays to deploying rescue PCI in CH patients were shortened over those previously achieved thereby resulting in similar outcomes to those randomized in the ambulance. Our results reinforce the benefits of functional hub and spoke models with rapid transfer to a PCI-capable facility.

Background Heart failure with reduced ejection fraction is increasingly prevalent in older adults, yet data on guideline-directed therapies in the oldest age groups remain limited. Objective To assess outcomes of sacubitril/valsartan in adults aged ≥75 years, across age strata (≥75, ≥80, ≥85, ≥90 years; 75–79, 80–84, 85– 89 years), focusing on cardiovascular, heart failure, and all-cause hospitalizations, and mortality. Methods This retrospective study evaluated all patients aged ≥ 75 years in Belgium with chronic heart failure with reduced ejection fraction who started sacubitril/valsartan between 1 November, 2016 and 31 December, 2018. Results A total of 1705 patients were divided into the following age groups: 75–79, 80–84, 85–89, and ≥ 90 years. Cardiovascular hospitalization rates significantly decreased across all age groups after sacubitril/valsartan initiation. Patients aged 75–79 years showed a reduction from 0.74 events/year (95% confidence interval [CI] 0.68–0.81) prior to treatment to 0.54 (95% CI 0.47–0.62, p < 0.001) after initiation. Rates fell from 0.73 (95% CI 0.66–0.80) to 0.53 (95% CI 0.44–0.65, p < 0.001) in those aged 80–84 years, from 0.62 (95% CI 0.52–0.74) to 0.44 (95% CI 0.35–0.57, p < 0.01) in those aged 85–89 years, and from 0.78 (95% CI 0.59–1.03) to 0.42 (95% CI 0.22–0.83, p < 0.01) in patients aged ≥ 90 years. Heart failure-related hospitalization rates also showed consistent reductions: 0.34 (95% CI 0.30–0.39) prior to treatment to 0.28 (95% CI 0.22–0.34) after initiation in patients aged 75–79 years, and from 0.38 (95% CI 0.33–0.43) to 0.30 (95% CI 0.23–0.39) in those aged 80–84 years (all p < 0.05). The rates decreased from 0.35 (95% CI 0.28–0.44) to 0.27 (95% CI 0.20–0.38, p = 0.08) in those aged 85–89 years and from 0.52 (95% CI 0.36–0.76) to 0.29 (95% CI 0.12–0.75, p < 0.05) in the oldest patients aged ≥ 90 years. Conclusions Broader application of guideline-directed medical therapy in geriatric heart failure with reduced ejection fraction care should be prioritized.

BACKGROUND: In STREAM-1 (Strategic Reperfusion Early After Myocardial Infarction), excess intracranial hemorrhage occurred in patients aged ≥75 years receiving full-dose tenecteplase as part of a pharmaco-invasive strategy, whereas no further intracranial hemorrhage occurred after halving the tenecteplase dose. In STREAM-2 (Second Strategic Reperfusion Early After Myocardial Infarction), half-dose tenecteplase was an effective and safe pharmaco-invasive strategy in older patients with ST-segment–elevation myocardial infarction presenting within P =0.277) and comparable composite end points (23.4% versus 28.0%; relative risk, 0.90 [95% CI, 0.62–1.30]; P =0.567) without occurrence of intracranial hemorrhage. CONCLUSIONS: Comparable efficacy exists between half- and full-dose tenecteplase pharmaco-invasive treatments with improved safety in patients with ST-segment–elevation myocardial infarction aged ≥75 years. Half-dose pharmaco-invasive therapy is a legitimate therapeutic option for elderly patients with ST-segment–elevation myocardial infarction unable to access timely primary PCI. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00623623. URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02777580.

BACKGROUND: No randomized data exist on ultrathin-strut stents in patients at high bleeding risk (HBR) undergoing an abbreviated dual antiplatelet therapy after coronary stenting. The aim of this study was to compare the safety and effectiveness of the ultrathin-strut biodegradable-polymer sirolimus-eluting Supraflex Cruz stent with the thin-strut biodegradable-polymer sirolimus-eluting Ultimaster Tansei stent in patients at HBR with abbreviated dual antiplatelet therapy after stenting. METHODS: In the investigator-initiated, randomized, open-label COMPARE 60/80 HBR trial (Comparison of the Supraflex Cruz 60 Micron Stent Strut Versus the Ultimaster Tansei 80 Micron Stent Strut in HBR Percutaneous Coronary Intervention Population), 741 patients at HBR according to the Academic Research Consortium HBR criteria were randomized to receive either the ultrathin-strut biodegradable-polymer sirolimus-eluting Supraflex Cruz stent or thin-strut biodegradable-polymer sirolimus-eluting Ultimaster Tansei stent. Dual antiplatelet therapy was recommended according to the applicable guidelines and trial data for patients at HBR. The primary outcome was net adverse clinical events, the composite of cardiovascular death, myocardial infarction, target vessel revascularization, stroke, and major bleeding, and was powered for noninferiority with an absolute margin of 4.0% at 1-sided 2.5% alpha. RESULTS: Between September 2020 and August 2022, 371 patients were randomized to the ultrathin-strut biodegradable-polymer sirolimus-eluting Supraflex Cruz stent and 370 patients to the thin-strut biodegradable-polymer sirolimus-eluting Ultimaster Tansei stent at 11 sites in the Netherlands. At 1 year, the primary outcome was observed in 56 (15.4%) patients in the ultrathin-strut biodegradable-polymer sirolimus-eluting Supraflex Cruz stent group and 61 (17.1%) in the thin-strut biodegradable-polymer sirolimus-eluting Ultimaster Tansei stent group (risk difference, −1.65%; upper boundary of the 1-sided 95% CI, 3.74; P =0.02 for noninferiority at a 0.025 significance level and P =0.55 for 2-sided superiority at a 0.05 significance level). CONCLUSIONS: Among patients at HBR with abbreviated dual antiplatelet therapy post-stenting, the use of an ultrathin-strut biodegradable-polymer sirolimus-eluting Supraflex Cruz stent was noninferior compared with the use of a thin-strut biodegradable-polymer sirolimus-eluting Ultimaster Tansei stent. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04500912.

Introduction/Aims: Magnetic resonance imaging (MRI) findings in peroneal neuropathy are not well documented and the prognostic value of imaging remains uncertain. Upper limits of cross‐sectional area (CSA) on ultrasound (US) have been established, but uncertainty regarding generalizability remains. We aimed to describe MRI findings of the peroneal nerve in patients and healthy controls and to compare these results to US findings and clinical characteristics.Methods: We prospectively included patients with foot drop and electrodiagnostically confirmed peroneal neuropathy, and performed clinical follow‐up, US and MRI of both peroneal nerves. We compared MRI findings to healthy controls. Two radiologists evaluated MRI features in an exploratory analysis after images were anonymized and randomized.Results: Twenty‐two patients and 38 healthy controls were included. Whereas significant increased MRI CSA values were documented in patients (mean CSA 20 mm² vs. 13 mm² in healthy controls), intra‐ and interobserver variability was substantial (variability of, respectively, 7 and 9 mm² around the mean in 95% of repeated measurements). A pathological T2 hyperintense signal of the nerve was found in 52.6% of patients (50% interobserver agreement). Increased CSA measurements (MRI/US), pathological T2 hyperintensity of the nerve and muscle edema were not predictive for recovery.Discussion: Imaging is recommended in all patients with peroneal neuropathy to exclude compressive intrinsic and extrinsic masses but we do not advise routine MRI for diagnosis or prediction of outcome in patients with peroneal neuropathy due to high observer variability. Further studies should aim at reducing MRI observer variability potentially by semi‐automation.