The Time–Reset Effect

Fiehler, Jens

doi:10.1007/s00062-017-0561-4

Cited by 11 publications

(6 citation statements)

References 13 publications

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“…Contrarily to Al Sultan and Hill, 16 arguing for an imprecise measurement of TTR, we hence favour TTR to be a more precise and meaningful parameter compared to STG. This view is in line with the 'time-reset effect', arguing for the quickest possible reperfusion once imaging identifies relevant salvageable tissue, 7 rendering time from imaging to reperfusion the main time dependence because of the used imaging selection. Distribution of mRS scores at 3 months, according to time to reperfusion strata.…”

Section: Discussionmentioning

confidence: 60%

“…Since almost all RCTs used some kind of imaging selection or other inclusion criteria, the true decline of TTR treatment effect when subjecting all AIS patients with a target LVO in the AC has and will probably never been elucidated. However, it is very important to keep in mind that the slope of decline in efficacy is strongly influenced by patient selection, 7 and treatment effect may be distinct also in late TTR as shown by recent DAWN and DEFUSE-3 RCTs. 3,4 In this registry, we observed heterogeneous aOR of TTR on good functional outcome for each centre (Supplementary Table 5), probably due to different approaches to patient selection.…”

Section: Discussionmentioning

confidence: 99%

“…6 Therefore, the decline of treatment effect seems to be strongly influenced by patient selection, and the concept of a general time window with an uniform decline of efficacy has been challenged. 7,8 Furthermore, it remains unclear whether with increasing time from symptom onset to reperfusion (TTR) there is a cut-off time with deleterious treatment effect thereafter similar to intravenous thrombolysis (IVT) or if MT at a given time point simply remains futile and not cost-effective. 9,10 The aims of this study were (1) to evaluate the clinical effect of TTR; and (2) to assess the safety and technical efficacy of MT according to strata of TTR.…”

Section: Introductionmentioning

confidence: 99%

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Outcome, efficacy and safety of endovascular thrombectomy in ischaemic stroke according to time to reperfusion: data from a multicentre registry

Meinel

Kaesmacher

Mordasini

et al. 2019

Ther Adv Neurol Disord

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Background and purpose: In acute ischaemic stroke (AIS) of the anterior circulation (AC) treated with mechanical thrombectomy (MT), data point to a decline of treatment effect with increasing time from symptom onset to treatment. However, the magnitude of the decline will depend on the clinical setting and imaging selection used. The aims of this study were (1) to evaluate the clinical effect of time to reperfusion (TTR); and (2) to assess the safety and technical efficacy of MT according to strata of TTR. Methods: Using the retrospective multicentre BEYOND-SWIFT registry data (ClinicalTrials.gov identifier: NCT03496064), we compared safety and efficacy of MT in 1461 patients between TTR strata of 0–180 min ( n = 192), 180–360 min ( n = 876) and >360 min ( n = 393). Clinical effect of TTR was evaluated using multivariable logistic regression analyses adjusting for pre-specified confounders [adjusted odds ratios (aOR) and 95% confidence intervals (95% CI)]. Primary outcome was good functional outcome (modified Rankin Scale: mRS 0–2) at day 90. Results: Every hour delay in TTR was a significant factor related to mRS 0–2 (aOR 0.933, 95% CI 0.887–0.981) with an estimated 1.5% decreased probability of good functional outcome per hour delay of reperfusion, and mRS 0–1 (aOR 0.929, 95% CI 0.877–0.985). Patients with late TTR had lower rates of successful and excellent reperfusion, higher complication rates and number of passes. Conclusions: TTR is an independent factor related to long-term functional outcome. With increasing TTR, interventional procedures become technically less effective. Efforts should be made to shorten TTR through optimized prehospital and in-hospital pathways.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Outcome, efficacy and safety of endovascular thrombectomy in ischaemic stroke according to time to reperfusion: data from a multicentre registry

Meinel

Kaesmacher

Mordasini

et al. 2019

Ther Adv Neurol Disord

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“… 5 The latter phenomenon concerning the effect of time on functional outcome, often referred to as the time-reset effect, is indeed well known: admission/imaging-to-groin intervals have a stronger association with outcome, as opposed to STA intervals, as also observed in this registry. 21 Given the less restrictive selection criteria of our patient cohort, however, one would expect this bias to be weaker, thereby potentially unmasking an underlying association.…”

Section: Discussionmentioning

confidence: 98%

Effect of Pre- and In-Hospital Delay on Reperfusion in Acute Ischemic Stroke Mechanical Thrombectomy

Kaesmacher

Maamari

Meinel

et al. 2020

Stroke

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Background and Purpose: Post hoc analyses of randomized controlled clinical trials evaluating mechanical thrombectomy have suggested that admission-to-groin-puncture (ATG) delays are associated with reduced reperfusion rates. Purpose of this analysis was to validate this association in a real-world cohort and to find associated factors and confounders for prolonged ATG intervals. Methods: Patients included into the BEYOND-SWIFT cohort (Bernese-European Registry for Ischemic Stroke Patients Treated Outside Current Guidelines With Neurothrombectomy Devices Using the Solitaire FR With the Intention for Thrombectomy; https://www.clinicaltrials.gov ; Unique identifier: NCT03496064) were analyzed (n=2386). Association between baseline characteristics and ATG was evaluated using mixed linear regression analysis. The effect of increasing symptom-onset-to-admission and ATG intervals on successful reperfusion (defined as Thrombolysis in Cerebral Infarction [TICI] 2b-3) was evaluated using logistic regression analysis adjusting for potential confounders. Results: Median ATG was 73 minutes. Prolonged ATG intervals were associated with the use of magnetic resonance imaging (+19.1 [95% CI, +9.1 to +29.1] minutes), general anesthesia (+12.1 [95% CI, +3.7 to +20.4] minutes), and borderline indication criteria, such as lower National Institutes of Health Stroke Scale, late presentations, or not meeting top-tier early time window eligibility criteria (+13.8 [95% CI, +6.1 to +21.6] minutes). There was a 13% relative odds reduction for TICI 2b-3 (adjusted odds ratio [aOR], 0.87 [95% CI, 0.79–0.96]) and TICI 2c/3 (aOR, 0.87 [95% CI, 0.79–0.95]) per hour ATG delay, while the reduction of TICI 2b-3 per hour increase symptom-onset-to-admission was minor (aOR, 0.97 [95% CI, 0.94–0.99]) and inconsistent regarding TICI 2c/3 (aOR, 0.99 [95% CI, 0.97–1.02]). After adjusting for identified factors associated with prolonged ATG intervals, the association of ATG delay and lower rates of TICI 2b-3 remained tangible (aOR, 0.87 [95% CI, 0.76–0.99]). Conclusions: There is a great potential to reduce ATG, and potential targets for improvement can be deduced from observational data. The association between in-hospital delay and reduced reperfusion rates is evident in real-world clinical data, underscoring the need to optimize in-hospital workflows. Given the only minor association between symptom-onset-to-admission intervals and reperfusion rates, the causal relationship of this association warrants further research. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03496064.

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“…The resulting selected patients are physiologically homogeneous, all having a propensity for rapid infarct growth in postarrival minutes. This phenomenon has been termed the time-reset effect by Fiehler . Second is the differential greater reliability of documented times in emergency department vs those for both unwitnessed and even witnessed stroke onset.…”

Section: Discussionmentioning

confidence: 99%

Healthy Life-Year Costs of Treatment Speed From Arrival to Endovascular Thrombectomy in Patients With Ischemic Stroke

et al. 2021

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The benefits of endovascular thrombectomy (EVT) are time dependent. Prior studies may have underestimated the time-benefit association because time of onset is imprecisely known.OBJECTIVE To assess the lifetime outcomes associated with speed of endovascular thrombectomy in patients with acute ischemic stroke due to large-vessel occlusion (LVO).DATA SOURCES PubMed was searched for randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time, and for which a peer-reviewed, complete primary results article was published by August 1, 2020.STUDY SELECTION All randomized clinical trials of stent retriever thrombectomy devices vs medical therapy in patients with anterior circulation LVO within 12 hours of last known well time were included.DATA EXTRACTION/SYNTHESIS Patient-level data regarding presenting clinical and imaging features and functional outcomes were pooled from the 7 retrieved randomized clinical trials of stent retriever thrombectomy devices (entirely or predominantly) vs medical therapy. All 7 identified trials published in a peer-reviewed journal (by August 1, 2020) contributed data. Detailed time metrics were collected including last known well-to-door (LKWTD) time; last known well/onset-to-puncture (LKWTP) time; last known well-to-reperfusion (LKWR) time; door-to-puncture (DTP) time; and door-to-reperfusion (DTR) time. MAIN OUTCOMES AND MEASURESChange in healthy life-years measured as disability-adjusted life-years (DALYs). DALYs were calculated as the sum of years of life lost (YLL) owing to premature mortality and years of healthy life lost because of disability (YLD). Disability weights were assigned using the utility-weighted modified Rankin Scale. Age-specific life expectancies without stroke were calculated from 2017 US National Vital Statistics. RESULTS Among the 781 EVT-treated patients, 406 (52.0%) were early-treated (LKWTP Յ4 hours) and 375 (48.0%) were late-treated (LKWTP >4-12 hours). In early-treated patients, LKWTD was 188 minutes (interquartile range, 151.3-214.8 minutes) and DTP 105 minutes (interquartile range, 76-135 minutes). Among the 298 of 380 (78.4%) patients with substantial reperfusion, median DTR time was 145.0 minutes (interquartile range, 111.5-185.5 minutes). Care process delays were associated with worse clinical outcomes in LKW-to-intervention intervals in early-treated patients and in door-to-intervention intervals in early-treated and late-treated patients, and not associated with LKWTD intervals, eg, in early-treated patients, for each 10-minute delay, healthy life-years lost were DTP 1.8 months vs LKWTD 0.0 months; P < .001. Considering granular time increments, the amount of healthy life-time lost associated with each 1 second of delay was DTP 2.2 hours and DTR 2.4 hours. CONCLUSIONS AND RELEVANCEIn this study, care delays were associated with loss of healthy life-years in patients with acute ischemic stroke treated with EVT, particularly in the postarrival time...

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The Time–Reset Effect

Cited by 11 publications

References 13 publications

Outcome, efficacy and safety of endovascular thrombectomy in ischaemic stroke according to time to reperfusion: data from a multicentre registry

Outcome, efficacy and safety of endovascular thrombectomy in ischaemic stroke according to time to reperfusion: data from a multicentre registry

Effect of Pre- and In-Hospital Delay on Reperfusion in Acute Ischemic Stroke Mechanical Thrombectomy

Healthy Life-Year Costs of Treatment Speed From Arrival to Endovascular Thrombectomy in Patients With Ischemic Stroke

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