Browsing by Subject "REPERFUSION"

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  • Stassen, Willem; Wallis, Lee; Castren, Maaret; Vincent-Lambert, Craig; Kurland, Lisa (2019)
    The incidence of cardiovascular disease and STEMI is on the rise in sub-Saharan Africa. Timely treatment is essential to reduce mortality. Internationally, prehospital 12 lead ECG telemetry has been proposed to reduce time to reperfusion. Its value in South Africa has not been established. The aim of this study was to determine the effect of prehospital 12 lead ECG telemetry on the PCI-times of STEMI patients in South Africa. A multicentre randomised controlled trial was attempted among adult patients with prehospital 12 lead ECG evidence of STEMI. Due to poor enrolment and small sample sizes, meaningful analyses could not be made. The challenges and lessons learnt from this attempt at Africa's first prehospital RCT are discussed. Challenges associated with conducting this RCT related to the healthcare landscape, resources, training of paramedics, rollout and rando-misation, technology, consent and research culture. High quality evidence to guide prehospital emergency care practice is lacking both in Africa and the rest of the world. This is likely due to the difficulties with performing prehospital clinical trials. Every trial will be unique to the test intervention and setting of each study, but by considering some of the challenges and lessons learnt in the attempt at this trial, future studies might experience less difficulty. This may lead to a stronger evidence-base for prehospital emergency
  • Koivula, Kimmo; Nikus, Kjell; Viikilä, Juho; Lilleberg, Jyrki; Huhtala, Heini; Birnbaum, Yochai; Eskola, Markku (2019)
    Background Both Q waves and T-wave inversion (TWI) in the presenting ECG are associated with a progressed stage of myocardial infarction, possibly with less potential for myocardial salvage with reperfusion therapy. Combining the diagnostic information from the Q- and T-wave analyses could improve the prognostic work-up in ST-elevation myocardial infarction (STEMI) patients. Methods We sought to determine the prognostic impact of Q waves and TWI in the admission ECG on patient outcome in STEMI. We formed four groups according to the presence of Q waves and/or TWI (Q+TWI+; Q-TWI+; Q+TWI-; Q-TWI-). We studied 627 all-comers with STEMI derived from two patient cohorts. Results The patients with Q+TWI+ had the highest and those with Q-TWI- the lowest 30-day and one-year mortality. One-year mortality was similar between Q-TWI+ and Q+TWI-. The survival analysis showed higher early mortality in Q+TWI- but the higher late mortality in Q-TWI+ compensated for the difference at 1 year. The highest peak troponin level was found in the patients with Q+TWI-. Conclusion Q waves and TWI predict adverse outcome, especially if both ECG features are present. Q waves and TWI predict similar one-year mortality. Extending the ECG analysis in STEMI patients to include both Q waves and TWI improves risk stratification.
  • Sarja, Henna; Anttila, Tuomas; Mustonen, Caius; Honkanen, Hannu-Pekka; Herajarvi, Johanna; Haapanen, Henri; Tuominen, Hannu; Miinalainen, Ilkka; Juvonen, Tatu; Anttila, Vesa (2017)
    Background: We hypothesized that diazoxide, a mitochondrial ATP-sensitive potassium channel opener, has cardioprotective effects during acute myocardial ischemia. Diazoxide is suggested to act through protein kinase Ce (PKC epsilon) activation. Methods: Twelve piglets were randomly assigned to receive intravenous infusion of diazoxide (3.5 mg/kg) with solvent or only solvent (6 animals per group) before cardiac ischemia. Myocardial ischemia was induced by occluding the left circumflex artery (LCX) for 40 minutes. The reperfusion and follow-up period lasted for three hours. Throughout the experiment hemodynamic measurements and blood samples were collected, and after the follow-up period the hearts were harvested for transmission electron microscopy (TEM) as well as histopathological and immunohistochemical analyses. Results: TEM showed less ischemic damage on a cellular level in the diazoxide group (P = .004) than in the control group. Creatinine kinase MB levels (Pt*g = .030) were lower, and oxygen consumption (Pt*g = .037) and delivery (Pg = .038) were higher in the diazoxide group compared to the controls. Conclusion: Diazoxide preserves myocardial cellular structure and cellular function, and thus it may have benefits in treating ischemic myocardial injury.
  • Humaloja, Jaana; Litonius, Erik; Efendijev, Ilmar; Folger, Daniel; Raj, Rahul; Pekkarinen, Pirkka T.; Skrifvars, Markus B. (2019)
    Aim: Studies suggest that hyperoxemia increases short-term mortality after cardiopulmonary resuscitation (CPR), but the effect of hyperoxemia on long-term outcomes is unclear. We determined the prevalence of early hyperoxemia after CPR and its association with long-term neurological outcome and mortality. Methods: We analysed data from adult cardiac arrest patients treated after CPR in tertiary ICUs during 2005-2013. We retrieved data from the resuscitation and the first arterial blood sample collected after return of spontaneous circulation (ROSC) (severe hyperoxemia defined as PaO2 > 40 kPa and moderate as PaO2 16-40 kPa). We inspected two outcomes, neurological performance at one year after resuscitation according to the Cerebral Performance Category and one-year mortality. We used logistic regression to test associations between hyperoxemia and the outcome and interaction analyses to test the effect of hyperoxemia exposure on the outcomes in smaller subgroups. Results: Of 1110 patients 11% had severe hyperoxemia, prevalence was 10% for out-of-hospital arrests, 13% for in-hospital arrests and 9% for in-ICU arrests. In total 585(53%) patients had an unfavourable neurological outcome. Compared to normoxemia, severe (Odds ratio [OR] 0.81, 95% confidence interval [CI] 0.50-1.30) and moderate hyperoxemia (OR 0.94 95%CI 0.69-1.27) did not associate with neurological outcome. Additionally, hyperoxemia had no association with mortality. In subgroup analyses there were no significant associations between severe hyperoxemia and outcomes regardless of cardiac arrest location, initial rhythm or time-to-ROSC. Conclusion: We found no association between early post-arrest hyperoxemia and unfavourable outcome, Subgroup analysis found no differential effect depending on arrest location, initial rhythm or time-to-ROSC.
  • EXTEND Investigator; ECASS-4 Investigator; EPITHET Investigator; Campbell, Bruce C.; Ma, Henry; Curtze, Sami; Donnan, Geoffrey A.; Kaste, Markku (2019)
    Background Stroke thrombolysis with alteplase is currently recommended 0-4.5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4.5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis. Methods In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials. gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged =18 years) with ischaemic stroke treated more than 4.5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. Findings We identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1.86, 95% CI 1.15-2.99, p=0.011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9.7, 95% CI 1.23-76.55, p=0.031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1.55, 0.81-2.96, p=0.66). Interpretation Patients with ischaemic stroke 4.5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis. Copyright (c) 2019 Elsevier Ltd. All rights reserved.
  • Pöyhönen, Pauli; Kylmälä, Minna; Vesterinen, Paula; Kivistö, Sari; Holmström, Miia; Lauerma, Kirsi; Väänänen, Heikki; Toivonen, Lauri; Hänninen, Helena (2018)
    Background: Large myocardial infarction (MI) is associated with adverse left ventricular (LV) remodeling (LVR). We studied the nature of LVR, with specific attention to non-transmural MIs, and the association of peak CK-MB with recovery and chronic phase scar size and LVR. Methods: Altogether 41 patients underwent prospectively repeated cardiovascular magnetic resonance at a median of 22 (interquartile range 9-29) days and 10 (8-16) months after the first revascularized MI. Transmural MI was defined as >= 75% enhancement in at least one myocardial segment. Results: Peak CK-MB was 86 (40-216) mu g/L in median, while recovery and chronic phase scar size were 13 (3-23) % and 8 (2-19) %. Altogether 33 patients (81%) had a non-transmural MI. Peak CK-MB had a strong correlation with recovery and chronic scar size (r >= 0.80 for all, r >= 0.74 for non-transmural MIs; p <0.001). Peak CK-MB, recovery scar size, and chronic scar size, were all strongly correlated with chronic wall motion abnormality index (WMAi) (r >= 0.75 for all, r >= 0.73 for non-transmural MIs; p <0.001). There was proportional scar size and LV mass resorption of 26% (0-50%) and 6% (-2-14%) in median. Young age (<60 years, median) was associated with greater LV mass resorption (median 9% vs. 1%, p = 0.007). Conclusions: Peak CK-MB has a strong association with chronic scar size and wall motion abnormalities after revascularized non-transmural MI. Considerable infarct resorption happens after the first-month recovery phase. LV mass resorption is related to age, being more common in younger patients.
  • Nauck, Michael A.; McGuire, Darren K.; Pieper, Karen S.; Lokhnygina, Yuliya; Strandberg, Timo E.; Riefflin, Axel; Delibasi, Tuncay; Peterson, Eric D.; White, Harvey D.; Scott, Russell; Holman, Rury R. (2019)
    Background To examine the effects of the DPP-4i sitagliptin on CV outcomes during and after incident MI in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Methods TECOS randomized 14,671 participants with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) to sitagliptin or placebo, in addition to usual care. For those who had a within-trial MI, we analyzed case fatality, and for those with a nonfatal MI, we examined a composite cardiovascular (CV) outcome (CV death or hospitalization for heart failure [hHF]) by treatment group, using Cox proportional hazards models left-censored at the time of the first within-trial MI, without and with adjustment for potential confounders, in intention-to-treat analyses. Results During TECOS, 616 participants had >= 1 MI (sitagliptin group 300, placebo group 316, HR 0.95, 95% CI 0.81-1.11, P = 0.49), of which 25 were fatal [11 and 14, respectively]). Of the 591 patients with a nonfatal MI, 87 (15%) died subsequently, with 66 (11%) being CV deaths, and 57 (10%) experiencing hHF. The composite outcome occurred in 58 (20.1%; 13.9 per 100 person-years) sitagliptin group participants and 50 (16.6%; 11.7 per 100 person-years) placebo group participants (HR 1.21, 95% CI 0.83-1.77, P = 0.32, adjusted HR 1.23, 95% CI 0.83-1.82, P = 0.31). On-treatment sensitivity analyses also showed no significant between-group differences in post-MI outcomes. Conclusions In patients with type 2 diabetes and ASCVD experiencing an MI, sitagliptin did not reduce subsequent risk of CV death or hHF, contrary to expectations derived from preclinical animal models. Trial registration clinicaltrials.gov no. NCT00790205
  • Jakkula, Pekka; Reinikainen, Matti; Hästbacka, Johanna; Pettilä, Ville; Loisa, Pekka; Karlsson, Sari; Laru-Sompa, Raili; Bendel, Stepani; Oksanen, Tuomas; Birkelund, Thomas; Tiainen, Marjaana; Toppila, Jussi; Hakkarainen, Antti; Skrifvars, Markus B.; COMACARE Study Grp (2017)
    Background: Arterial carbon dioxide tension (PaCO2), oxygen tension (PaO2), and mean arterial pressure (MAP) are modifiable factors that affect cerebral blood flow (CBF), cerebral oxygen delivery, and potentially the course of brain injury after cardiac arrest. No evidence regarding optimal treatment targets exists. Methods: The Carbon dioxide, Oxygen, and Mean arterial pressure After Cardiac Arrest and REsuscitation (COMACARE) trial is a pilot multi-center randomized controlled trial (RCT) assessing the feasibility of targeting low-or high-normal PaCO2, PaO2, and MAP in comatose, mechanically ventilated patients after out-of-hospital cardiac arrest (OHCA), as well as its effect on brain injury markers. Using a 23 factorial design, participants are randomized upon admission to an intensive care unit into one of eight groups with various combinations of PaCO2, PaO2, and MAP target levels for 36 h after admission. The primary outcome is neuron-specific enolase (NSE) serum concentration at 48 h after cardiac arrest. The main feasibility outcome is the between-group differences in PaCO2, PaO2, and MAP during the 36 h after ICU admission. Secondary outcomes include serum concentrations of NSE, S100 protein, and cardiac troponin at 24, 48, and 72 h after cardiac arrest; cerebral oxygenation, measured with near-infrared spectroscopy (NIRS); potential differences in epileptic activity, monitored via continuous electroencephalogram (EEG); and neurological outcomes at six months after cardiac arrest. Discussion: The trial began in March 2016 and participant recruitment has begun in all seven study sites as of March 2017. Currently, 115 of the total of 120 patients have been included. When completed, the results of this trial will provide preliminary clinical evidence regarding the feasibility of targeting low-or high-normal PaCO2, PaO2, and MAP values and its effect on developing brain injury, brain oxygenation, and epileptic seizures after cardiac arrest. The results of this trial will be used to evaluate whether a larger RCT on this subject is justified.
  • Helve, Salla; Viikila, Juho; Laine, Mika; Lilleberg, Jyrki; Tierala, Ilkka; Nieminen, Tuomo (2014)