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Critical limb threatening ischemia (CLTI) is associated with a one-year mortality rate of up to 25% making prompt diagnosis essentially. This study aims to investigate if cardiac biomarkers may serve as an effective tool for risk stratification in patients with lower extremity artery disease (LEAD). For this cross-sectional retrospective analysis, 21712 patients with LEAD were screened for eligibility from 2004 to 2020. Out of these patients, 367 were included and subdivided into those with CLTI and those without CLTI. Cardiac biomarkers, including N-terminal prohormone of brain natriuretic peptide (NT-proBNP), troponin, NT-proBNP/troponin ratio, creatin kinase myocardial band (CK-MB) and myoglobin, were retrospectively analyzed. Fifty-nine patients had CLTI (16.1%) with higher rates of NT-proBNP, NT-proBNP/troponin ratio, CK-MB and myoglobin (all p < 0.05) compared to non-CLTI patients. In univariate analysis, NT-proBNP, NT-proBNP/troponin ratio, CK-MB, myoglobin, age, C-reactive protein and non-insulin dependent diabetes mellitus (NIDDM) were associated with CLTI (all p < 0.05). In multivariate analysis, age and NIDDM remained significant predictors (all p < 0.05) while cardiac biomarkers were not independently associated with CLTI. Troponin, NT-proBNP and myoglobin were associated with mortality in univariate analysis (all p < 0.05). In multivariate analysis, troponin only remains to be associated with mortality (p = 0.001). Selected cardiac biomarkers failed to demonstrate statistically significant differentiation between CLTI and non-CLTI patients with LEAD, while troponin may be potentially associated with mortality.

•Randomized evidence regarding the optimal revascularization strategey in NSTEMI patients with multivessel coronary artery disease is limited.•The COMPLETE-NSTEMI trail aims to investigate whether complete revascularization is superior over culprit-lesion only PCI in these patients.•This trial will enroll 3390 NSTEMI patients at 65 to 70 in Germany and Austria. Multivessel coronary artery disease (CAD) is present in 30% to 70% of patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI) depending on varying age and risk profiles. In contrast to the STEMI cohort, there is only limited scientific evidence derived from randomized controlled trials directing the general decision for or against complete revascularization in the NSTEMI population. The COMPLETE-NSTEMI trial aims to investigate whether multivessel percutaneous coronary intervention (PCI) is superior over culprit-lesion only PCI in patients with NSTEMI and multivessel CAD. COMPLETE-NSTEMI is a prospective, randomized, controlled, multicenter, parallel group, open-label trial. It will enroll 3390 NSTEMI patients with multivessel CAD at 65 to 70 sites in Germany and Austria. Patients will be randomized 1:1 to either complete revascularization with PCI or culprit lesion-only PCI. The primary efficacy endpoint is a composite of cardiovascular death or rehospitalization for nonfatal myocardial infarction during follow-up. The trial is event-driven and will be stopped as soon as 578 primary endpoint events and a minimal follow-up duration of 12 months for each patient are reached. The first patient was enrolled at October 27, 2023. By April 2025, 51 sites have been activated and >500 patients have been randomized. Completion of recruitment is expected for the first half of 2027. The final results of the primary endpoint are expected in 2028. COMPLETE NSTEMI will be the first dedicated trial to answer the question about the optimal revascularization strategy in patients with NSTEMI and multivessel CAD. NCT05786131

Computer models of left ventricular (LV) electro-mechanics (EM) show promise as a tool for assessing the impact of increased afterload upon LV performance. However, the identification of unique afterload model parameters and the personalization of EM LV models remains challenging due to significant clinical input uncertainties. Here, we personalized a virtual cohort of N  = 17 EM LV models under pressure overload conditions. A global–local optimizer was developed to uniquely identify parameters of a three-element Windkessel (Wk3) afterload model. The sensitivity of Wk3 parameters to input uncertainty and of the EM LV model to Wk3 parameter uncertainty was analysed. The optimizer uniquely identified Wk3 parameters, and outputs of the personalized EM LV models showed close agreement with clinical data in all cases. Sensitivity analysis revealed a strong dependence of Wk3 parameters on input uncertainty. However, this had limited impact on outputs of EM LV models. A unique identification of Wk3 parameters from clinical data appears feasible, but it is sensitive to input uncertainty, thus depending on accurate invasive measurements. By contrast, the EM LV model outputs were less sensitive, with errors of less than 8.14% for input data errors of 10%, which is within the bounds of clinical data uncertainty. This article is part of the theme issue ‘Uncertainty quantification in cardiac and cardiovascular modelling and simulation’.

Multivessel coronary artery disease (CAD) is present in 30-70% of patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI) depending on varying age and risk profiles. In contrast to the STEMI cohort, there is only limited scientific evidence derived from randomized controlled trials directing the general decision for or against complete revascularization in the NSTEMI population.BACKGROUNDMultivessel coronary artery disease (CAD) is present in 30-70% of patients presenting with non-ST-segment elevation myocardial infarction (NSTEMI) depending on varying age and risk profiles. In contrast to the STEMI cohort, there is only limited scientific evidence derived from randomized controlled trials directing the general decision for or against complete revascularization in the NSTEMI population.The COMPLETE-NSTEMI trial aims to investigate whether multivessel percutaneous coronary intervention (PCI) is superior over culprit-lesion only PCI in patients with NSTEMI and multivessel CAD.PRIMARY HYPOTHESISThe COMPLETE-NSTEMI trial aims to investigate whether multivessel percutaneous coronary intervention (PCI) is superior over culprit-lesion only PCI in patients with NSTEMI and multivessel CAD.COMPLETE-NSTEMI is a prospective, randomized, controlled, multicenter, parallel group, open-label trial. It will enroll 3390 NSTEMI patients with multivessel CAD at 65 to 70 sites in Germany and Austria. Patients will be randomized 1:1 to either complete revascularization with PCI or culprit lesion-only PCI.DESIGNCOMPLETE-NSTEMI is a prospective, randomized, controlled, multicenter, parallel group, open-label trial. It will enroll 3390 NSTEMI patients with multivessel CAD at 65 to 70 sites in Germany and Austria. Patients will be randomized 1:1 to either complete revascularization with PCI or culprit lesion-only PCI.The primary efficacy endpoint is a composite of cardiovascular death or rehospitalization for non-fatal myocardial infarction during follow-up. The trial is event-driven and will be stopped as soon as 578 primary endpoint events and a minimal follow-up duration of 12 months for each patient are reached.ENDPOINTSThe primary efficacy endpoint is a composite of cardiovascular death or rehospitalization for non-fatal myocardial infarction during follow-up. The trial is event-driven and will be stopped as soon as 578 primary endpoint events and a minimal follow-up duration of 12 months for each patient are reached.The first patient was enrolled at October 27, 2023. By April 2025, 51 sites have been activated and >500 patients have been randomized. Completion of recruitment is expected for the first half of 2027. The final results of the primary endpoint are expected in 2028.CURRENT STATUSThe first patient was enrolled at October 27, 2023. By April 2025, 51 sites have been activated and >500 patients have been randomized. Completion of recruitment is expected for the first half of 2027. The final results of the primary endpoint are expected in 2028.COMPLETE NSTEMI will be the first dedicated trial to answer the question about the optimal revascularization strategy in patients with NSTEMI and multivessel CAD.OUTLOOKCOMPLETE NSTEMI will be the first dedicated trial to answer the question about the optimal revascularization strategy in patients with NSTEMI and multivessel CAD.CLINICALTRIALS.GOV: NCT05786131.TRIAL REGISTRATIONCLINICALTRIALS.GOV: NCT05786131.

Computer models of left ventricular (LV) electro-mechanics (EM) show promise as a tool for assessing the impact of increased afterload upon LV performance. However, the identification of unique afterload model parameters and the personalization of EM LV models remains challenging due to significant clinical input uncertainties. Here, we personalized a virtual cohort of N = 17 EM LV models under pressure overload conditions. A global–local optimizer was developed to uniquely identify parameters of a three-element Windkessel (Wk3) afterload model. The sensitivity of Wk3 parameters to input uncertainty and of the EM LV model to Wk3 parameter uncertainty was analysed. The optimizer uniquely identified Wk3 parameters, and outputs of the personalized EM LV models showed close agreement with clinical data in all cases. Sensitivity analysis revealed a strong dependence of Wk3 parameters on input uncertainty. However, this had limited impact on outputs of EM LV models. A unique identification of Wk3 parameters from clinical data appears feasible, but it is sensitive to input uncertainty, thus depending on accurate invasive measurements. By contrast, the EM LV model outputs were less sensitive, with errors of less than 8.14% for input data errors of 10%, which is within the bounds of clinical data uncertainty. This article is part of the theme issue ‘Uncertainty quantification in cardiac and cardiovascular modelling and simulation’.

Current guidelines recommend potent platelet inhibition with prasugrel or ticagrelor for 12 months after an acute coronary syndrome managed with percutaneous coronary intervention (PCI). However, the greatest anti-ischaemic benefit of potent antiplatelet drugs over the less potent clopidogrel occurs early, while most excess bleeding events arise during chronic treatment. Hence, a stage-adapted treatment with potent platelet inhibition in the acute phase and de-escalation to clopidogrel in the maintenance phase could be an alternative approach. We aimed to investigate the safety and efficacy of early de-escalation of antiplatelet treatment from prasugrel to clopidogrel guided by platelet function testing (PFT). In this investigator-initiated, randomised, open-label, assessor-blinded, multicentre trial (TROPICAL-ACS) done at 33 sites in Europe, patients were enrolled if they had biomarker-positive acute coronary syndrome with successful PCI and a planned duration of dual antiplatelet treatment of 12 months. Enrolled patients were randomly assigned (1:1) using an internet-based randomisation procedure with a computer-generated block randomisation with stratification across study sites to either standard treatment with prasugrel for 12 months (control group) or a step-down regimen (1 week prasugrel followed by 1 week clopidogrel and PFT-guided maintenance therapy with clopidogrel or prasugrel from day 14 after hospital discharge; guided de-escalation group). The assessors were masked to the treatment allocation. The primary endpoint was net clinical benefit (cardiovascular death, myocardial infarction, stroke or bleeding grade 2 or higher according to Bleeding Academic Research Consortium [BARC]) criteria) 1 year after randomisation (non-inferiority hypothesis; margin of 30%). Analysis was intention to treat. This study is registered with ClinicalTrials.gov, number NCT01959451, and EudraCT, 2013-001636-22. Between Dec 2, 2013, and May 20, 2016, 2610 patients were assigned to study groups; 1304 to the guided de-escalation group and 1306 to the control group. The primary endpoint occurred in 95 patients (7%) in the guided de-escalation group and in 118 patients (9%) in the control group (pnon-inferiority=0·0004; hazard ratio [HR] 0·81 [95% CI 0·62–1·06], psuperiority=0·12). Despite early de-escalation, there was no increase in the combined risk of cardiovascular death, myocardial infarction, or stroke in the de-escalation group (32 patients [3%]) versus in the control group (42 patients [3%]; pnon-inferiority=0·0115). There were 64 BARC 2 or higher bleeding events (5%) in the de-escalation group versus 79 events (6%) in the control group (HR 0·82 [95% CI 0·59–1·13]; p=0·23). Guided de-escalation of antiplatelet treatment was non-inferior to standard treatment with prasugrel at 1 year after PCI in terms of net clinical benefit. Our trial shows that early de-escalation of antiplatelet treatment can be considered as an alternative approach in patients with acute coronary syndrome managed with PCI. Klinikum der Universität München, Roche Diagnostics, Eli Lilly, and Daiichi Sankyo.