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Browsing by Author "Olavarría, Verónica V."

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Associations of Early Systolic Blood Pressure Control and Outcome After Thrombolysis- Eligible Acute Ischemic Stroke: Results From the ENCHANTED Study
(2022) Wang, Xia; Minhas, Jatinder S.; Moullaali, Tom J.; Di Tanna, Gian Luca; Lindley, Richard I.; Chen, Xiaoying; Arima, Hisatomi; Chen, Guofang; Delcourt, Candice; Bath, Philip M.; Broderick, Joseph P.; Demchuk, Andrew M.; Donnan, Geoffrey A.; Durham, Alice C.; Lavados, Pablo; Lee, Tsong-Hai; Levi, Christopher; Martins, Sheila O.; Olavarría, Verónica V.; Pandian, Jeyaraj D.; Parsons, Mark W.; Pontes-Neto, Octavio M.; Ricci, Stefano; Sato, Shoichiro; Sharma, Vijay K.; Silva, Federico; Thang, Nguyen H.; Wang, Ji-Guang; Woodward, Mark; Chalmers, John; Song, Lili; Anderson, Craig S.; Robinson, Thompson G.
BACKGROUND AND PURPOSE: In thrombolysis-eligible patients with acute ischemic stroke, there is uncertainty over the most appropriate systolic blood pressure (SBP) lowering profile that provides an optimal balance of potential benefit (functional recovery) and harm (intracranial hemorrhage). We aimed to determine relationships of SBP parameters and outcomes in thrombolyzed acute ischemic stroke patients. METHODS: Post hoc analyzes of the ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study), a partial-factorial trial of thrombolysis-eligible and treated acute ischemic stroke patients with high SBP (150–180 mm Hg) assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) alteplase and intensive (target SBP, 130–140 mm Hg) or guideline-recommended (target SBP <180 mm Hg) treatment. All patients were followed up for functional status and serious adverse events to 90 days. Logistic regression models were used to analyze 3 SBP summary measures postrandomization: attained (mean), variability (SD) in 1–24 hours, and magnitude of reduction in 1 hour. The primary outcome was a favorable shift on the modified Rankin Scale. The key safety outcome was any intracranial hemorrhage. RESULTS: Among 4511 included participants (mean age 67 years, 38% female, 65% Asian) lower attained SBP and smaller SBP variability were associated with favorable shift on the modified Rankin Scale (per 10 mm Hg increase: odds ratio, 0.76 [95% CI, 0.71–0.82]; P<0.001 and 0.86 [95% CI, 0.76–0.98]; P=0.025) respectively, but not for magnitude of SBP reduction (0.98, [0.93– 1.04]; P=0.564). Odds of intracranial hemorrhage was associated with higher attained SBP and greater SBP variability (1.18 [1.06–1.31]; P=0.002 and 1.34 [1.11–1.62]; P=0.002) but not with magnitude of SBP reduction (1.05 [0.98–1.14]; P=0.184). CONCLUSIONS: Attaining early and consistent low levels in SBP <140 mm Hg, even as low as 110 to 120 mm Hg, over 24 hours is associated with better outcomes in thrombolyzed acute ischemic stroke patients.
Correlation between dual-phase CTA-SI ASPECTS and automated CT perfusion imaging in patients with acute ischemic stroke beyond the 6-hour window
(2023) Gallardo, Andrés; Lavados, Pablo; Cox, Pablo; Barra, Camila de la; Cavada, Gabriel; Olavarría, Verónica V.
Background/Objective: There is controversy regarding the need to use advanced imaging to select candidates for thrombectomy in late window acute ischemic stroke (AIS). Hypoattenuation on CT angiography source images (CTA-SI) in arterial phase has been shown to be more sensitive than Alberta Stroke Program Early CT Score (ASPECTS) of brain parenchyma to determine tissue at risk of ischemia. Our hypothesis is that the addition of a second acquisition at 35-50 seconds could complement the assessment of hypoperfused tissue that fails to receive flow through pial vessels. Methods: Patients with large vessel occlusion and 6-24 hours from symptom onset, admitted between August 2019 and July 2023, were evaluated with dual-phase CT angiography (CTA) and CT-Perfusion. A vascular neurologist estimated CTA-SI ASPECTS in both phases at the time of data entry into the RECCA registry. In contrast, the post-processing of CT-Perfusion images was performed in an automated way through RAPID© software. The association between automated CT-perfusion values and dual-phase CTA-SI ASPECTS was assessed through a correlation coefficient. Results: Pearson’s coefficient demonstrated a high correlation between ischemic core volume and delayed phase CTA (CTA-DP) ASPECTS with an inverse association of −0.93 and between Tmax ≥ 6 sec volume and arterial phase CTA (CTA-AP) ASPECTS with a value of −0.88. Conclusions: CTA-derived source images (CTA-SI) in two phases may be useful in the selection of patients with AIS presenting beyond the 6-hour window.
Diffusion-weighted imaging as predictor of acute ischemic stroke etiology
(2022) brunser, alejandro; Mansilla, Eloy; NAVIA, VICTOR; Mazzon, Enrico; Rojo, Alexis; Cavada, Gabriel; Olavarría, Verónica V.; Munoz Venturelli, Paula; Lavados, Pablo
Background: Topographic patterns may correlate with causes of ischemic stroke. Objective: To investigate the association between diffusion weighted imaging (DWI) and Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Methods: We included 1019 ischemic stroke patients. DWI were classified as: i) negative; ii) DWI single lesion (cortico-subcortical, cortical, subcortical ≥20 mm, or subcortical <20 mm); iii) scattered lesions in one territory (small scattered lesions or confluent with additional lesions); and iv) multiple lesions (multiple unilateral anterior circulation [MAC], multiple posterior circulation [MPC], multiple bilateral anterior circulation [MBAC], and multiple anterior and posterior circulations [MAP]). Results: There was a relationship between DWI patterns and TOAST classification (p<0.001). Large artery atherosclerosis was associated with small, scattered lesions in one vascular territory (Odds Ratio [OR] 4.22, 95% confidence interval [95%CI] 2.61–6.8), MPC (OR 3.52; 95%CI 1.54–8.03), and subcortical lesions <20 mm (OR 3.47; 95%CI 1.76–6.85). Cardioembolic strokes correlated with MAP (OR 4.3; 95%CI 1.64–11.2), cortico-subcortical lesions (OR 3.24; 95%CI 1.9–5.5) and negative DWI (OR 2.46; 95%CI 1.1–5.49). Cryptogenic strokes correlated with negative DWI (OR 4.1; 95%CI 1,84–8.69), cortical strokes (OR 3.3; 95%CI 1.25–8.8), MAP (OR 3.33; 95%CI 1.25–8.81) and subcortical lesion ≥20 mm (OR 2.44; 95%CI 1,04–5.73). Lacunar strokes correlated with subcortical lesions diameter <20 mm (OR 42.9; 95%CI 22.7–81.1) and negative DWI (OR 8.87; 95%CI 4.03–19.5). Finally, MBAC (OR 9.25; 95%CI 1.12–76.2), MAP (OR 5.54; 95%CI 1.94–15.1), and MPC (OR 3.61; 95%CI 1.5–8.7) correlated with stroke of other etiologies. Conclusions: A relationship exists between DWI and stroke subtype
Effects of intensive blood pressure lowering on cerebral ischaemia in thrombolysed patients: insights from the ENCHANTED trial
(2023) Chen, Chen; Ouyang, Menglu; Ong, Sheila; Zhang, Luyun; Zhang, Guobin; Delcourt, Candice; Mair, Grant; Liu, Leibo; Billot, Laurent; Li, Qiang; Chen, Xiaoying; Parsons, Mark; Broderick, Joseph; Demchuk, Andrew; Bath, Philip; Donnan, Geoffrey; Levi, Christopher; Chalmers, John; Lindley, Richard; Martins, Sheila; Pontes-Neto, Octavio; Munoz Venturelli, Paula; Olavarría, Verónica V.; Lavados, Pablo; Robinson, Thompson; Wardlaw, Joanna; Li, Gang; Wang, Xia; Song, Lili; Anderson, Craig
Background: Intensive blood pressure lowering may adversely affect evolving cerebral ischaemia. We aimed to determine whether intensive blood pressure lowering altered the size of cerebral infarction in the 2196 patients who participated in the Enhanced Control of Hypertension and Thrombolysis Stroke Study, an international randomised controlled trial of intensive (systolic target 130-140 mm Hg within 1 h; maintained for 72 h) or guideline-recommended (systolic target <180 mm Hg) blood pressure management in patients with hypertension (systolic blood pressure >150 mm Hg) after thrombolysis treatment for acute ischaemic stroke between March 3, 2012 and April 30, 2018. Methods: All available brain imaging were analysed centrally by expert readers. Log-linear regression was used to determine the effects of intensive blood pressure lowering on the size of cerebral infarction, with adjustment for potential confounders. The primary analysis pertained to follow-up computerised tomography (CT) scans done between 24 and 36 h. Sensitivity analysis were undertaken in patients with only a follow-up magnetic resonance imaging (MRI) and either MRI or CT at 24-36 h, and in patients with any brain imaging done at any time during follow-up. This trial is registered with ClinicalTrials.gov, number NCT01422616. Findings: There were 1477 (67.3%) patients (mean age 67.7 [12.1] y; male 60%, Asian 65%) with available follow-up brain imaging for analysis, including 635 patients with a CT done at 24-36 h. Mean achieved systolic blood pressures over 1-24 h were 141 mm Hg and 149 mm Hg in the intensive group and guideline group, respectively. There was no effect of intensive blood pressure lowering on the median size (ml) of cerebral infarction on follow-up CT at 24-36 h (0.3 [IQR 0.0-16.6] in the intensive group and 0.9 [0.0-12.5] in the guideline group; log Δmean -0.17, 95% CI -0.78 to 0.43). The results were consistent in sensitivity and subgroup analyses. Interpretation: Intensive blood pressure lowering treatment to a systolic target <140 mm Hg within several hours after the onset of symptoms may not increase the size of cerebral infarction in patients who receive thrombolysis treatment for acute ischaemic stroke of mild to moderate neurological severity. Funding: National Health and Medical Research Council of Australia; UK Stroke Association; UK Dementia Research Institute; Ministry of Health and the National Council for Scientific and Technological Development of Brazil; Ministry for Health, Welfare, and Family Affairs of South Korea; Takeda.
Incidence, risk factors, prognosis, and health-related quality of life after stroke in a low-resource community in Chile (ÑANDU): a prospective population-based study
(2021) Lavados, Pablo; Hoffmeister, Lorena; Moraga, Ana M.; Vejar, Angélica; Vidal, Carolina; Gajardo, Constanza; Portales, María Bernardita; San Martín, Daniela; López, Eduardo; Rojo, Alexis; Olavarría, Verónica V.; Almeida, Juan; Brunser, Alejandro M.; Muñoz Venturelli, Paula; Hoppe, Arnold; Díaz, Violeta; Sacks, Claudio
Background Stroke is a leading cause of disability and death worldwide. The best estimates of local, national, and global burden of stroke are derived from prospective population-based studies. We aimed to investigate the incidence, risk factors, long-term prognosis, care, and quality of life after stroke in the Ñuble region of Chile. Methods We did a prospective community-based study with use of multiple overlapping sources of hospitalised, ambulatory, and deceased cases. Standardised diagnostic criteria were used to identify and follow up all cases occurring in the resident population of the Ñuble region, Chile (in a low-income rural-urban population including predominantly people of Indigenous-European heritage), for 1 year. Participants were included if they had a clinical diagnosis of stroke confirmed according to the study criteria. All cases were adjudicated by vascular neurologists. Incidence rates of first-ever stroke were calculated from the population of Ñuble according to the 2017 national census. Findings From April 1, 2015, to March 31, 2016, we ascertained 1103 stroke cases, of which 890 (80·7%) were first-ever incident cases. The mean age of patients with first-ever stroke was 70·3 years (SD 14·1) and 443 (49·8%) were women. A CT scan was obtained in 801 (90%) of 890 patients (mean time from symptom onset to scan of 13·4 h (SD 29·8). The incidence of first-ever stroke age-adjusted to the world population was 121·7 (95% CI 113·7–130·1) per 100 000. The age-adjusted incidence rates, per 100000 inhabitants, by main pathological subtypes were as follows: ischaemic stroke (101·5 [95% CI 90·9–113·0]); intracerebral haemorrhage (17·9 [13·5–23·4]), and subarachnoid haemorrhage (4·2 [2·1–7·3]). The 30-day case-fatality rate was 24·6% (21·9–27·6). At 6 months after the stroke, 55·9% (432 of 773) of cases had died or were disabled, which increased to 61·0% (456 of 747) at 12 months. Health-related quality of life in survivors was low at 6 months, improving slightly at 12 months after the stroke. Interpretation The incidence of stroke in this low-resource population was higher than our previous finding in northern Chile and within the mid-range of most population-based stroke studies. This result was due mainly to a higher incidence of ischaemic stroke, probably associated with increasing age and a high prevalence of cardiometabolic risk factors in the population studied. Our findings suggest that more should be done for the prevention and care of stroke in communities like the Ñuble population. Funding The National Agency for Research and Development and the Technology-Health Research Fund, Clínica Alemana de Santiago, Boehringer Ingelheim, Bristol Meyers Squibb, The Herminda Martin Clinical Hospital of Chillán, Universidad Mayor, and Universidad de Concepción.
Low blood pressure and adverse outcomes in acute stroke: HeadPoSTstudy explanations
(2021) Muñoz Venturelli, Paula; Billota, Laurent; Wang, Xia; Ouyang, Menglu; Song, Lili; Arima, Hisatomi; Lavados, Pablo; Hackett, Maree L.; Olavarría, Verónica V.; Brunser, Alejandro; Middleton, Sandy; Pontes-Neto, Octavio M.; Lee, Tsong-Hai; Watkins, Caroline L.; Robinson, Thompson; Anderson, Craig S.
Objective: As uncertainties exist over underlying causes, we aimed to define the characteristics and prognostic significance of low blood pressure (BP) early after the onset of acute stroke. Methods: Post hoc analyzes of the international Head Positioning in acute Stroke Trial (HeadPoST), a pragmatic cluster-crossover randomized trial of lying flat versus sitting up in stroke patients from nine countries during 2015-2016. Associations of baseline BP and death or dependency [modified Rankin scale (mRS) scores 3-6] and serious adverse events (SAEs) at 90 days were assessed in generalized linear mixed models with adjustment for multiple confounders. SBP and DBP was analysed as continuous measures fitted with a cubic spline, and as categorical measures with low (<10th percentile) and high (≥140 and ≥90 mmHg, respectively) levels compared with a normal range (≥10th percentile; 120-139 and 70-89 mmHg, respectively). Results: Among 11 083 patients (mean age 68 years, 39.9% women) with baseline BP values, 7.2 and 11.7% had low SBP (<120 mmHg) and DBP (<70 mmHg), respectively. Patients with low SBP were more likely to have preexisting cardiac and ischemic stroke and functional impairment, and to present earlier with more severe neurological impairment than other patients. Nonlinear 'J-shaped' relationships of BP and poor outcome were apparent: compared with normal SBP, those with low SBP had worse functional outcome (adjusted odds ratio 1.27, 95% confidence interval 1.02-1.58) and more SAEs, particularly cardiac events, with adjustment for potential confounders to minimize reverse causation. The findings were consistent for DBP and were stronger for ischemic rather than hemorrhagic stroke. Conclusion: The prognostic significance of low BP on poor outcomes in acute stroke was not explained by reverse causality from preexisting cardiovascular disease, and propensity towards greater neurological deficits and cardiac events. These findings provide support for the hypothesis that low BP exacerbates cardiac and cerebral ischemia in acute ischemic stroke.
Oxygen desaturation and adverse outcomes in acute stroke: Secondary analysis of the HeadPoST study
(2021) Ouyang, Menglu; Roffe, Christine; Billot, Laurent; Song, Lili; Wang, Xia; Muñoz Venturelli, Paula; Lavados, Pablo; Robinson, Thompson; Middleton, Sandy; Olavarría, Verónica V.; Watkins, Caroline L.; Lee, Tsong-Hai; Brunser, Alejandro M.; Pontes-Neto, Octavio M.; Hackett, Maree L.
Objective: Uncertainty exists over the prognostic significance of low arterial oxygen saturation (SaO2) in acute stroke. We aimed to determine the strength of association of SaO2 and adverse outcomes among participants of the international Head Positioning in acute Stroke Trial (HeadPoST). Methods: Post-hoc analyzes of HeadPoST, a pragmatic cluster-crossover randomized trial of lying flat versus sitting up head positioning in 11,093 patients (age ≥18 years) with acute stroke at 114 hospitals in 9 countries during 2015–2016. Associations of the lowest recorded SaO2 level, as a continuous measure and as a cut-point for desaturation (SaO2 <93%), in the first 24 h and clinical outcomes of death or dependency (modified Rankin scale [mRS] scores 3–6) and any serious adverse event (SAE) at 90 days, were assessed in generalized linear mixed models adjusted for baseline and in-hospital management confounders. Results: There was an inverse J-shaped association between SaO2 and death or dependency, with a nadir for optimal outcome at 96–97%. Patients with SaO2 desaturation were older, and had greater neurological impairment, premorbid disability and cardiorespiratory disease. Desaturation was not clearly associated with death or dependency (adjusted odds ratio [aOR] 1.19, 95% confidence interval [CI] 0.95–1.48) but was with SAEs (aOR 1.34, 95% CI 1.07–1.68), without heterogeneity by head position, cardiac-respiratory comorbidity, or other pre-specified subgroups. Conclusions: Any change in SaO2 outside of 96–97% is associated with poorer outcome after acute stroke. Clinical trial registration: HeadPoST is registered at ClinicalTrials.gov (NCT02162017).
Who is in the emergency room matters when we talk about door-to-needle time: a single-center experience
(2023) brunser, alejandro; Nuñez, Juan Cristobal; Mansilla, Eloy; Cavada, Gabriel; Olavarría, Verónica V.; Munoz Venturelli, Paula; Lavados, Pablo
Background: The efficacy of intravenous thrombolysis (IVT) is time-dependent. Objective: To compare the door-to-needle (DTN) time of stroke neurologists (SNs) versus non-stroke neurologists (NSNs) and emergency room physicians (EPs). Additionally, we aimed to determine elements associated with DTN ≤ 20 minutes. Methods: Prospective study of patients with IVT treated at Clínica Alemana between June 2016 and September 2021. Results: A total of 301 patients underwent treatment for IVT. The mean DTN time was 43.3 ± 23.6 minutes. One hundred seventy-three (57.4%) patients were evaluated by SNs, 122 (40.5%) by NSNs, and 6 (2.1%) by EPs. The mean DTN times were 40.8 ± 23, 46 ± 24.7, and 58 ± 22.5 minutes, respectively. Door-to-needle time ≤ 20 minutes occurred more frequently when patients were treated by SNs compared to NSNs and EPs: 15%, 4%, and 0%, respectively (odds ratio [OR]: 4.3, 95% confidence interval [95%CI]: 1.66-11.5, p = 0.004). In univariate analysis DTN time ≤ 20 minutes was associated with treatment by a SN (p = 0.002), coronavirus disease 2019 pandemic period (p = 0.21), time to emergency room (ER) (p = 0.21), presence of diabetes (p = 0.142), hypercholesterolemia (p = 0.007), atrial fibrillation (p < 0.09), score on the National Institutes of Health Stroke Scale (NIHSS) (p = 0.001), lower systolic (p = 0.143) and diastolic (p = 0.21) blood pressures, the Alberta Stroke Program Early CT Score (ASPECTS; p = 0.09), vessel occlusion (p = 0.05), use of tenecteplase (p = 0.18), thrombectomy (p = 0.13), and years of experience of the physician (p < 0.001). After multivariate analysis, being treated by a SN (OR: 3.95; 95%CI: 1.44-10.8; p = 0.007), NIHSS (OR: 1.07; 95%CI: 1.02-1.12; p < 0.002) and lower systolic blood pressure (OR: 0.98; 95%CI: 0.96-0.99; p < 0.003) remained significant. Conclusion: Treatment by a SN resulted in a higher probability of treating the patient in a DTN time within 20 minutes.
Who is in the emergency room matters when we talk about door-to-needle time: a single-center experience [Quien está en el servicio de emergencia importa al hablar de tiempo puerta-aguja: experiencia de un centro clínico]
(2023) brunser, alejandro; Nuñez; Juan; Mansilla, Eloy; Cavada, Gabriel; Olavarría, Verónica V.; Munoz Venturelli, Paula; Lavados, Pablo
Background: The efficacy of intravenous thrombolysis (IVT) is time-dependent. Objective: To compare the door-to-needle (DTN) time of stroke neurologists (SNs) versus non-stroke neurologists (NSNs) and emergency room physicians (EPs). Additionally, we aimed to determine elements associated with DTN ≤ 20 minutes. Methods: Prospective study of patients with IVT treated at Clínica Alemana between June 2016 and September 2021. Results: A total of 301 patients underwent treatment for IVT. The mean DTN time was 43.3 ± 23.6 minutes. One hundred seventy-three (57.4%) patients were evaluated by SNs, 122 (40.5%) by NSNs, and 6 (2.1%) by EPs. The mean DTN times were 40.8 ± 23, 46 ± 24.7, and 58 ± 22.5 minutes, respectively. Door-to-needle time ≤ 20 minutes occurred more frequently when patients were treated by SNs compared to NSNs and EPs: 15%, 4%, and 0%, respectively (odds ratio [OR]: 4.3, 95% confidence interval [95%CI]: 1.66–11.5, p = 0.004). In univariate analysis DTN time ≤ 20 minutes was associated with treatment by a SN ( p = 0.002), coronavirus disease 2019 pandemic period ( p = 0.21), time to emergency room (ER) ( p = 0.21), presence of diabetes ( p = 0.142), hypercholesterolemia ( p = 0.007), atrial fibrillation ( p < 0.09), score on the National Institutes of Health Stroke Scale (NIHSS) ( p = 0.001), lower systolic ( p = 0.143) and diastolic ( p = 0.21) blood pressures, the Alberta Stroke Program Early CT Score (ASPECTS; p = 0.09), vessel occlusion ( p = 0.05), use of tenecteplase ( p = 0.18), thrombectomy ( p = 0.13), and years of experience of the physician ( p < 0.001). After multivariate analysis, being treated by a SN (OR: 3.95; 95%CI: 1.44–10.8; p = 0.007), NIHSS (OR: 1.07; 95%CI: 1.02–1.12; p < 0.002) and lower systolic blood pressure (OR: 0.98; 95%CI: 0.96–0.99; p < 0.003) remained significant. Conclusion: Treatment by a SN resulted in a higher probability of treating the patient in a DTN time within 20 minutes.

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