Benefit Of Reperfusion Therapy Research Articles

Diagnosis and Management of Atrial Fibrillation in Acute Ischemic Stroke in the Setting of Reperfusion Therapy: Insights and Strategies for Optimized Care.

Reperfusion therapy in the form of intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT) has revolutionised the field of stroke medicine. Atrial fibrillation (AF) patients constitute a major portion of the overall stroke population; however, the prevalence of AF amongst acute ischemic stroke (AIS) patients receiving reperfusion therapy remains unclear. Limitations in our understanding of prevalence in this group of patients are exacerbated by difficulties in appropriately diagnosing AF. Additionally, the benefits of reperfusion therapy are not consistent across all subgroups of AIS patients. More specifically, AIS patients with AF often tend to have poor prognoses despite treatment relative to those without AF. This article aims to present an overview of the diagnostic and therapeutic management of AF and how it mediates outcomes following stroke, most specifically in AIS patients treated with reperfusion therapy. We provide unique insights into AF prevalence and outcomes that could allow healthcare professionals to optimise the treatment and prognosis for AIS patients with AF. Specific indications on acute neurovascular management and secondary stroke prevention in AIS patients with AF are also discussed.

Hospital service for ischemic stroke patients in Brazilian countryside: are we still in the '80s?

Stroke is one of the most common causes of death and incapacity in the world. The benefits of reperfusion therapies and hospitalization in neurologic intensive care units (ICUs) are undeniable. However, these treatments are not widely available in a continental-sized country like Brazil. To describe the treatment for ischemic stroke and the functional outcome 90 days after the hospitalization of patients in the Brazilian countryside. Observational, prospective case series study design. The data collected refer to randomly selected patients hospitalized in 3 hospitals in the south region of the state of Bahia between December 2018 and December 2019. The population consisted of 61 consecutive patients. They were elderly (median age: 62 years old); with a predominance of hypertension (82%); and were light to moderate stroke cases (National Institute of Health Stroke Scale [NIHSS] median: 7). A total of 37.7% of the cases arrived at the hospital in a < 4.5-hour window but received no reperfusion therapy. Of these, 94.3% were discharged from the hospital with a prescription for antiplatelets or anticoagulant. A total of 64.1% of the patients received a statin prescription. At the end of the follow-up period, the general mortality was 21%. Almost half of the population (47.9%) evolved to an unfavored outcome (modified Rankin scale [mRs]: 3 to 6). Our population presented sociodemographic and comorbidities characteristics similar to those of other national samples. No reperfusion therapy was used and the treatment was basically secondary and prophylaxis-oriented, and almost half of the population evolved with incapacities and a high mortality rate, despite the initial low clinical gravity.

Intramyocardial Hemorrhage and the “Wave Front” of Reperfusion Injury Compromising Myocardial Salvage

BackgroundReperfusion therapy for acute myocardial infarction (MI) is lifesaving. However, the benefit of reperfusion therapy can be paradoxically diminished by reperfusion injury, which can increase MI size. ObjectivesHemorrhage is known to occur in reperfused MIs, but whether hemorrhage plays a role in reperfusion-mediated MI expansion is not known. MethodsWe studied cardiac troponin kinetics (cTn) of ST-segment elevation MI patients (n = 70) classified by cardiovascular magnetic resonance to be hemorrhagic (70%) or nonhemorrhagic following primary percutaneous coronary intervention. To isolate the effects of hemorrhage from ischemic burden, we performed controlled canine studies (n = 25), and serially followed both cTn and MI size with time-lapse imaging. ResultsCTn was not different before reperfusion; however, an increase in cTn following primary percutaneous coronary intervention peaked earlier (12 hours vs 24 hours; P < 0.05) and was significantly higher in patients with hemorrhage (P < 0.01). In hemorrhagic animals, reperfusion led to rapid expansion of myocardial necrosis culminating in epicardial involvement, which was not present in nonhemorrhagic cases (P < 0.001). MI size and salvage were not different at 1 hour postreperfusion in animals with and without hemorrhage (P = 0.65). However, within 72 hours of reperfusion, a 4-fold greater loss in salvageable myocardium was evident in hemorrhagic MIs (P < 0.001). This paralleled observations in patients with larger MIs occurring in hemorrhagic cases (P < 0.01). ConclusionsMyocardial hemorrhage is a determinant of MI size. It drives MI expansion after reperfusion and compromises myocardial salvage. This introduces a clinical role of hemorrhage in acute care management, risk assessment, and future therapeutics.

Imaging as a Selection Tool for Thrombectomy in Acute Ischemic Stroke: Pathophysiologic Considerations.

Large vessel occlusion (LVO) stroke represents a stroke subset associated with the highest morbidity and mortality. Multiple prospective randomized trials have shown that thrombectomy, alone or in conjunction with IV thrombolysis, is highly effective in reestablishing cerebral perfusion and improving clinical outcomes. In unselected patients and especially in patients with poor collaterals, the benefit of reperfusion therapy is exquisitely time sensitive; the earlier thrombectomy is started, the lower the likelihood of disability or death. Understanding both the pathophysiologic underpinnings and the modifying factors of this strong time-to-treatment effect demonstrated in numerous randomized clinical trials is important for implementation of intrahospital workflow measures to maximize time efficiency of thrombectomy. Reducing delays in reperfusion therapy initiation has become a priority in acute stroke care, and therefore a thorough understanding of the main systems-based factors responsible for these delays is critical. Because the time spent evaluating the patient in the emergency department, which typically includes neuroimaging studies performed in scanners remote from the angiography suite, represents the main source of delays in thrombectomy initiation, the direct to angiography (DTA) model has emerged as a means to substantially reduce treatment times and is being instituted at an increasing number of thrombectomy centers across the world. The aim of this report is to introduce DTA as an emerging stroke care paradigm for patients with suspicion of LVO stroke, review results from studies evaluating its feasibility and impact on outcomes, describe current barriers to its more widespread adoption, and propose potential solutions to overcoming these barriers.

Predictors of mortality in patients with intermediate risk pulmonary embolism

Abstract Introduction Information about treatment and outcome of patients with pulmonary embolism (PE) intermediate risk remains limited. Little is known about the benefits of reperfusion therapy in patients with intermediate risk PE and evidence of right ventricular dysfunction. Objective To evaluate clinical outcomes and predictors of mortality in patients admitted to ICU with pulmonary embolism and intermediate risk. Methods In a prospective single-center study 103 normotensive patients with an established diagnosis of pulmonary embolism confirmed by pulmonary CT were included. All patients met intermediate risk criteria according to the European Society of Cardiology guidelines (ESC 2019) for pulmonary embolism using severity index [PESI] with signs of right ventricular dysfunction and elevated cardiac biomarkers. The average age of patients was 67.6 years (95% CI, 65.1–70.5), 42 (41%) of them were men. Thrombolysis with standard dose of alteplase was performed in 54 (52%) patients. CT scan and echocardiography were done for all patients. Results Outcome data were collected for all patients through the 30-day and 180-day follow-up. During 30 days follow up 14 patients died (13,6%, 95% CI, 6,9–20%). The all-cause mortality rate after 180 days was 22,2% (95% CI, 13,5–31%) - 22 patient. In the thrombolysis group only 2 patients died after 180-day follow-up, mortality rate was 4,4% (95% CI, 1,7–10,6%), the mortality rate in patients not treated by thrombolysis was 40% (95% CI, 25,3–54,7%). Thrombolysis was associated with a significant decrease in mortality [OR 0.07 (95% CI, 0.01–0.31)]. In the thrombolysis group 2 patients (4.1%; 95% CI, 1.1–10%) had a non-fatal major bleeding event. The presence of chronic heart failure [OR 6 (95% CI, 1.8–20.2)] and previous stroke [OR 4.3 (95% CI, 0.9–21.1)] were higher among non-survivors when compared to survivors (p≤0.05). TAPSE less than 16 mm was found to be negatively associated with survival [OR 5.5 (95% CI, 0.9–40.3)], p=0.02. Conclusion In our study thrombolysis in patients with pulmonary embolism and intermediate-risk was associated with improved prognosis. Predictors of mortality were the presence of CHF, previous stroke and TAPSE of less than 16 mm. Funding Acknowledgement Type of funding sources: None. Kaplan-Meier mortality curves. p&amp;lt;0.05

Predicting Clinical Outcome in Acute Ischemic Stroke Using Parallel Multi-parametric Feature Embedded Siamese Network.

Stroke is the second leading cause of death and disability worldwide, with ischemic stroke as the most common type. The preferred diagnostic procedure at the acute stage is the acquisition of multi-parametric magnetic resonance imaging (MRI). This type of imaging not only detects and locates the stroke lesion, but also provides the blood flow dynamics that helps clinicians in assessing the risks and benefits of reperfusion therapies. However, evaluating the outcome of these risky therapies beforehand is a complicated task due to the variability of lesion location, size, shape, and cerebral hemodynamics involved. Though the fully automated model for predicting treatment outcomes using multi-parametric imaging would be highly valuable in clinical settings, MRI datasets acquired at the acute stage are mostly scarce and suffer high class imbalance. In this paper, parallel multi-parametric feature embedded siamese network (PMFE-SN) is proposed that can learn with few samples and can handle skewness in multi-parametric MRI data. Moreover, five suitable evaluation metrics that are insensitive to imbalance are defined for this problem. The results show that PMFE-SN not only outperforms other state-of-the-art techniques in all these metrics but also can predict the class with a small number of samples, as well as the class with high number of samples. An accuracy of 0.67 on leave one cross out testing has been achieved with only two samples (minority class) for training and accuracy of 0.61 with the highest number of samples (majority class). In comparison, state-of-the-art using hand crafted features has 0 accuracy for minority class and 0.33 accuracy for majority class.

Stroke patient's alarm choice: General practitioner or emergency medical services.

ObjectivesStroke patients should be treated as soon as possible since the benefit of reperfusion therapies is highly time‐dependent. The proportion of patients eligible for reperfusion therapy is still limited, as many patients do not immediately alarm healthcare providers. The choice of healthcare system entrance influences the time of arrival in the hospital. Therefore, we assessed differences in these choices to obtain insight for strategies to reduce time delays in acute stroke patients.Materials and MethodsPatients with suspected acute stroke admitted to the participating hospitals received a questionnaire. We assessed differences between patients who initially alarmed the general practitioner (GP) and patients who directly alarmed the emergency medical services (EMS). Additionally, we assessed regional differences and patient trajectories after medical help was sought.ResultsWe included 163 patients. Most patients alarmed the GP as primary healthcare provider (n = 104; 64%), and median onset‐to‐door times were longer in these patients (466 minutes [IQR 149–1586]) compared to patients directly alarming the EMS (n = 59; 36%) (90 minutes [IQR 45–286]). This was even more pronounced in less densely populated areas. Patients who alarmed the GP first, more often had patient delay >15 minutes, hesitated to burden healthcare providers and underestimated symptomatology.ConclusionsOur results showed that patients who alarmed the GP first instead of the EMS differed in several factors that are potentially modifiable. Strategies to achieve reduction of vital prehospital time delays and to improve patient outcome are optimizing public awareness campaigns and GP triage along with adjusting current guidelines by enabling and focusing on immediate involvement of the EMS once acute stroke is suspected.

Abstract TP62: Frequency, Characteristics, and Outcomes of Acute Ischemic Stroke Patients With “Total Mismatch” on Penumbral Imaging Before Reperfusion Therapy

Background: When penumbral imaging shows “total mismatch” (large perfusion lesion and no irreversibly infarcted core), the entirety of jeopardized brain is still salvageable and the benefits of reperfusion therapy may be enhanced. The frequency, characteristics, and reperfusion therapy outcomes of total mismatch patients has not been well-characterized. Methods: Analysis of consecutive acute cerebral ischemia patients in anterior circulation undergoing CT or MR penumbral imaging prior to intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT). Patients were classified in four groups: 1) total mismatch (core 0% of perfusion lesion), 2) non-total but substantial mismatch (core 1-20% of perfusion lesion), 3) moderate or no mismatch (core 20-100% of perfusion lesion), and 4) small perfusion lesion (perfusion lesion volume &lt;10 ml). Results: Among 180 patients, pretreatment imaging patterns were: total mismatch 28.9%, substantial mismatch 22.8%, moderate or no mismatch 22.8%, and small perfusion lesion 25.6%. Among total mismatch patients, the Tmax&gt;6 sec perfusion lesion volume was 56.5 ml (IQR 28.3-85.6) and time from last known well to imaging was 89 mins (IQR 65-296). Compared to moderate patients, clinical features of total mismatch patients were: older (76.0 vs 65.9, p=0.006), lower NIHSS (median 12 vs 18, p=0.019), and more cardioembolism (76.9% vs 48.8%, p=0.005). Total mismatch patients more often had CT than MR (65.4% vs 14.6%, p=0.000), less ICA occlusion (15.4% vs 34.1%, p=0.035), and smaller perfusion lesions (median 56.5 vs 82.1 ml, p=0.007). Total mismatch patients were treated with combined IVT+EVT in 32.7%, IVT alone in 26.9%, and EVT alone in 40.4%. Freedom from disability (mRS 0-1) at discharge was more frequent, 35.6% vs 16.2%, p=0.049 and disability levels at day 90 were lower in total mismatch patients, mean mRS 2.7 vs 3.9, p=0.029. Conclusion: Total mismatch is present in one-quarter of patients undergoing reperfusion therapy, more often in older patients with cardioembolism as etiology of stroke. Total mismatch patients have better disability outcomes from reperfusion therapy, but more than half show disability indicating need for more complete reperfusion.

The Recognition-Response Gap in Acute Stroke: Examining the Relationship between Stroke Recognition and Response in a General Population Survey

Background: Benefits of reperfusion therapies in acute ischemic stroke are highly time-dependent. It is crucial that people who witness the onset of symptoms call emergency medical services (EMS) immediately. The aim of this study was to examine whether there is a gap between recognition of stroke and responding correctly by calling EMS using a scenario-based measure. Methods: Population-based survey of 1406 individuals from Newcastle upon Tyne, UK, examining stroke recognition and response knowledge using 12 scenario-based vignettes. The response rate was 32% out of 5000 contacted individuals. In total, 16,574 responses to scenarios were examined to investigate whether respondents would recognise stroke symptoms and indicate to call EMS immediately. Results: In 16% of cases people recognised stroke but did not correctly respond by indicating to call EMS. In 49% of responses people recognised stroke and would respond correctly, while in 31% of cases people both failed to correctly recognise and failed to identify the correct response to the stroke scenario. In 5% of cases stroke was not identified but a correct response was indicated. When stroke was recognised, in 25% of responses people indicated that they would not call EMS. Recognition self-efficacy and response self-efficacy were associated with correct response. Conclusions: A recognition-response gap was identified among UK adults in hypothetical scenarios concerning stroke. Both recognition and translation to adequate EMS response should be explicitly addressed in interventions aiming to improve witness response to stroke. Self-efficacy may be a promising target to close the recognition-response gap.

Abstract TP41: Perfusion CT Identifies Ischemic Stroke Patients With a Good Natural History Regardless of Treatment

Introduction: There remains uncertainty about the benefits of reperfusion therapy in minor stroke. In this study we tested the hypothesis that patients with a small perfusion lesions do not show clinical benefit from reperfusion therapy when using conventional outcome scores such as the modified Rankin scale. Methods: A prospective cohort of consecutive ischemic stroke patients who fulfilled standard clinical/NCCT eligibility criteria with additional perfusion and angiography CT before treatment with iv alteplase were collected. Volumetric CT perfusion was retrospectively analysed to identify patients with a small perfusion lesion (defined as a delay time lesion 3 seconds &lt;15mL). The primary analysis compared 3-month mRS as well as acute and 24 hour NIHSS scores in patients with a small perfusion lesion who were treated with rtPA against those who were not using linear regression to generate and odds ratios (OR). Results: Of the 1526 patients who were potentially eligible for alteplase therapy, 356 had a perfusion lesion &lt;15mL with 211 being treated and 145 not treated with rtPA. Patients with a small perfusion lesion had similar NIHSS between those who were treated and those not treated (rtPA treated small lesion patients acute NIHSS, 8.2, untreated 8.9, p=0.71). The odds of small lesion patients achieving mRS 0-1 with alteplase was 0.614 (p&lt;0.001). Average 24 hour DWI lesion in treated small perfusion lesion patients 3mL with alteplase treatment and 2.1mL without, p=0.081. The subgroup of patients with a small perfusion lesion associated with a vessel occlusion did however show an improvement in functional outcome (mRS 0-1OR 1.21, p=0.012). Conclusion: Ischemic stroke patients with a small perfusion lesion appear to have an excellent natural history regardless of alteplase treatment. Patients with a visible vessel occlusion may have a slight benefit from treatment.

1 The cathepsin-L inhibitor CAA0225 protects against myocardial ischaemia-reperfusion injury

Ischaemia-reperfusion (IR) injury contributes to the cardiac damage following myocardial infarction and paradoxically reduces the benefits of reperfusion therapy. In patients with ischaemic heart disease, cathepsin-L is elevated in the serum and correlates with disease severity. Our data demonstrate that cathepsin-L released from ex vivo rat hearts after ischaemia, and the cathepsin-L inhibitor CAA0225 improves cardiac function during ischaemia-reperfusion ex vivo . However, the effects of the CAA0225 in in vivo hearts during ischaemia-reperfusion are unknown. We hypothesised that using CAA0225 in an in vivo mouse model of ischaemia-reperfusion would identify the role cathepsin-L plays during ischaemia-reperfusion. Ischaemia-reperfusion injury was induced by 45 min temporary coronary artery ligation and CAA0225 was given by intra-venous injection during ischaemia before reperfusion. Double-dye staining demonstrated no difference in area at risk between groups whereas CAA0225 significantly reduced infarct size to 73% of control. Echocardiography demonstrated significantly preserved left ventricular fractional shortening at 2 wk and 4 wk post-IR in CAA0225 treated mice compared with control mice. PV loop measurements demonstrated CAA0225 treated mice had higher developed pressure than control mice at 2 weeks post-IR. Ex vivo isolated rat cardiomyocytes demonstrated that ischemia-reperfusion increased calcium influx through L-type calcium channels, reduced sarcolemmal NCX extrusion and SERCA activity. While CAA0225 treatment normalised the abnormalities of intracellular calcium handling parameters back to control thus reducing calcium waves following ischaemia-reperfusion. These data demonstrate for the first time that CAA0225 protects against ischaemia-reperfusion injury in mice and the mechanism relates to the normalisation of abnormal calcium handling following ischaemia-reperfusion injury.

Abstract 413: Engineering Targeted Growth Factors for Selective Pro-survival Signaling in Apoptotic Cardiomyocytes Following Ischemic Injury

Background: Despite the benefits of reperfusion therapy after myocardial infarction (MI), most patients still progress to heart failure. MI patients suffer irreversible loss of heart function due to cardiomyocyte (CM) death and tissue scarring. Growth factors (GFs) reduce scar size and limit CM apoptosis in preclinical studies, however native GFs have poor drug-like qualities and have not been successful in the clinic. Silver Creek Pharmaceuticals is developing a new class of targeted, growth factor-based therapeutics (Smart Growth Factors) that are engineered to have optimized pharmacokinetics, dynamics and safety profiles. Our first generation of SGFs use annexin-V (AnxV) to target IGF-1 to damaged CMs and selectively activate pro-survival signaling. Methods and Results: We used biophysical simulation to design an IGF-1-based SGF that selectively activated the PI3K pathway in damaged cells. SGFs were engineered to target IGF-1 to damaged cells through the binding of AnxV to phosphatidylserine exposed on the surface of apoptotic cells. These bispecific proteins were constructed with half-life modulators and linkers, then screened for their ability to selectively increase pAKT levels in apoptotic iPSC-derived human CMs. We identified a subset of SGFs that were able to selectively increase pAKT levels in apoptotic cells as compared to healthy cells (p&lt;0.05). Based on these data, we tested the ability of SGFs to activate pro-survival signaling and reduce infarct size in a rat ischemia/reperfusion model of acute MI (AMI). SGFs were able to selectively prolong pAKT in the infarcted region of the left ventricle without activating signaling in remote healthy tissue out to 2 hours post-reperfusion (n=3-6/group, p&lt;0.05). For efficacy studies, rats were subjected to 60 minutes of ischemia followed by 72 hours of reperfusion. A single IV dose of SGF (600 pmol/kg) administered at time of reperfusion was able to significantly reduce infarct size relative to the area-at-risk (infarct/AAR%) as compared to controls (p&lt;0.05; SGF 12.7±5% n=10; wt IGF-1 20.3±3% n=8 and vehicle 27.6±7% n=12). Conclusions: This work demonstrates that SGFs selectively activate pro-survival signals in distressed CMs and lead to reduced infarct size in vivo without off-target effects.

Abstract 233: Engineering Growth Factors For Cardiomyocyte Survival and Regeneration Following Ischemic Injury

Background: Despite the benefits of reperfusion therapy after myocardial infarction (MI), one-year mortality and morbidity rates remain high. Silver Creek Pharmaceuticals is engineering a new class of protein therapeutics, termed Smart Growth Factors (SGFs), designed to act directly on cardiomyocytes (CMs) to promote survival and regeneration after ischemia/reperfusion (I/R) injury. Our approach is to maximize pro-survival growth factor signaling in damaged cells by creating targeted molecules with optimized pharmacokinetics and dynamics. Methods and Results: Computer model simulations guided the design of a panel of SGFs comprising various growth factors, targeting arms, half-life modulators, and linkers. SGF constructs were cloned and subsequently produced using a HEK 293F expression system. This panel was screened in vitro for signaling pathway activation and target affinity. The top hits were assayed for pro-survival activity in a chemical injury model in human CMs, where a targeted SGF significantly reduced caspase activation (p&lt;0.0084; SGF-treated 3.82±0.64-fold, IGF1-treated 16.25±3.6-fold) Based on these data and additional simulations, a class of SGFs that utilized annexin V to target IGF1 to apoptotic cells via phosphatidylserine binding was selected for screening in animal models. In vivo, these SGFs extended pAKT signaling in heart tissue compared to wild-type IGF1 and had increased accumulation in the infarcted region of mouse hearts after MI. Preliminary data suggests that a single low intravenous dose (16 pmol) of SGF delivered one hour after LAD ligation could significantly reduce scar size in animals assessed at 12 weeks post MI (p&lt;0.05; SGF-treated 9.3±1.3%, n=10; vehicle 18.1±3.13%, n=8). Finally, SGF treatment at the time of reperfusion in a rat I/R model was able to significantly reduce infarct size (p&lt;0.05; SGF-treated 27.0±1.8% n=7; vehicle 33.6±1.92% n=8). Conclusions: This work demonstrates an enhanced ability of SGFs in preventing apoptosis in vitro and reducing infarct sizes in animal models of MI. By taking a systems biology approach to SGF engineering, Silver Creek is developing cardioprotective therapies with the hope of improving patient health and addressing unmet medical need.

Costs and benefits of treatment of myocardial infarction

Few treatments have been introduced in recent decades which are as effective as the modern treatment of myocardial infarction, based on rapid diagnosis (often by ambulance personnel, before admission to a hospital), immediate referral for reperfusion therapy (preferably by PCI), early discharge and subsequent intensive medical treatment for secondary prevention. The need for immediate PCI places a great burden on the medical staff (interventional cardiologists, nurses, technicians) of the hospital since many procedures need to be performed outside ‘normal’ working hours. Nevertheless such treatment is offered to most patients in the Netherlands admitted with ST-segment elevation on the ECG (STEMI) because the benefits are undisputable. Long-term follow-up of the study of reperfusion therapy by the Interuniversity Cardiology Institute in The Netherlands (ICIN) revealed that the early benefits of reperfusion therapy were sustained during 20 years, with a gain in life expectancy of 2.8 years [1]! The additional costs of reperfusion therapy during the first year after hospital admission were estimated at Dfl 7000 (€ 3200) [2], which amounts to only Dfl 2500 (€ 1150) per life-year saved! Further improvement of therapy for myocardial infarction was achieved by primary PCI as developed in Zwolle [3]. Indeed, systematic application of primary PCI resulted in a major further improvement of survival. For example, survival after 3 years of patients admitted with STEMI to the Thoraxcentre improved from 75% in the last decade of the previous century to 87% thereafter [4]. This represents a 48% reduction in mortality! In this issue of the journa lS oekhlal et al. report an analysis of current treatment costs of myocardial infarction in the Netherlands [5]. According to their calculations treatment costs for STEMI including PCI are about € 5700 and for patients with STEMI treated without PCI about € 4300. This is a modest difference of € 1400, well worth the benefits. Direct PCI is very cost-effective therapy. However, to my regret, the authors do not mention these benefits and present only costs. The authors indicate that their calculations may be used to support decision-making in health care, but such decision-making should also take into account the benefits of the treatment. Indeed, treatment of myocardial infarction carries a cost, but it should be seen as investment, an investment in health, an investment resulting in a significantly improved longevity and quality of life! Few interventions are as cost-effective as primary PCI.

Can Restoring Incomplete Microcirculatory Reperfusion Improve Stroke Outcome after Thrombolysis?

Substantial experimental data and recent clinical evidence suggesting that tissue reperfusion is a better predictor of outcome after thrombolysis than recanalization necessitate that patency of microcirculation after recanalization should be reevaluated. If indeed microcirculatory blood flow cannot be sufficiently reinstituted despite complete recanalization as commonly observed in coronary circulation, it may be one of the factors contributing to low efficacy of thrombolysis in stroke. Although microvascular no-reflow is considered an irreversible process that prevents tissue recovery from injury, emerging evidence suggests that it might be reversed with pharmacological agents administered early during recanalization. Therefore, therapeutic approaches aiming at reducing microvascular obstructions may improve success rate of recanalization therapies. Importantly, promoting oxygen delivery to the tissue, where entrapped erythrocytes cannot circulate in capillaries, with ongoing serum flow may improve survival of the underreperfused tissue. Altogether, these developments bring about the exciting possibility that benefit of reperfusion therapies can be further improved by restoring microcirculatory function because survival in the penumbra critically depends on adequate blood supply. Here, we review the available evidence suggesting presence of an 'incomplete microcirculatory reperfusion' (IMR) after focal cerebral ischemia and discuss potential means that may help investigate IMR in stroke patients after recanalization therapies despite technical limitations.

Abstract 3851: Temporal Distribution of Stroke Volumes and Clinical-Diffusion Mismatch in Patients with Proximal Arterial Occlusions

Background and Purpose: Previous studies have demonstrated that the benefit of reperfusion therapy declines over time. The Clinical-Diffusion Mismatch (CDM) model has been suggested as surrogate for salvable tissue in acute ischemic stroke (AIS) patients. We sought to describe the temporal behavior profile of infarct volumes and CDM in patients suffering AIS due to proximal arterial occlusion (PAO). Methods: We performed a retrospective analysis of consecutive AIS patients admitted to two large academic institutions fulfilling the following criteria: (1) Baseline NIHSS ≥8; (2) PAO defined as MCA-M1, intracranial ICA, or tandem cervical + ICA/MCA-M1 occlusion on admission CTA/MRA; and (3) MRI-DWI performed ≤8 hours from time of stroke onset/last seen well (TSO). CDM was defined as baseline NIHSS ≥8 and DWI volume ≤25cc (as proposed by Davalos et al). Linear regression analysis was performed to define the changes on DWI lesion volume on presentation over time. The observed TSO to MRI were broken down into quartiles to look for any differences in the distribution of the baseline variables over time. Results: A total of 132 consecutive patients were identified (mean age, 66±16.8 years; 57% females; mean baseline NIHSS 17.5±5.3; occlusion site: MCA-M1, 64%; intracranial-ICA, 29%; tandem, 5%, mean TSO to DWI, 269.5±105.48 minutes). The mean DWI stroke volume on presentation was 46.7±54.8 cc (range, 0.19-436.1) and 63 (46.7%) patients had CDM. There was no significant changes in age, gender, baseline NIHSS, or occlusion site amongst the different time quartiles. Median infarct volume (cc) increased (quartile #1=8.5; #2=30.1; #3=38.5; #4=29.4) and the chances of having a CDM decreased (p&lt;0.0001) across the different time quartiles. However, there was an overall poor correlation between DWI lesion volume on presentation and TSO to MRI (R-square=0.031, Figure ) and a significant proportion of the patients still had a CDM at later time epochs (#1=91.1%[20/22]; #2=47.8%[11/23]; #3=34.4%[21/61]; #4=42.3%[11/26]). Conclusions: Although infarct volume increases and the amount of penumbral tissue decreases over time, many patients with PAO will still have salvable penumbra at the later time epochs. This reflects individual differences in anatomic and physiological characteristics including the strength of collateral flow and highlights that selected patients may benefit from reperfusion therapy even at the later time windows. Figure : Relationship between Baseline DWI Volume (cc) and Time (minutes). Line is best fitted linear regression model.

Modelo de intervención coronaria percutánea primaria en la Comunidad de Navarra

El tratamiento del infarto agudo de miocardio ha evolucionado notablemente en las últimas tres décadas. Actualmente están establecidas con total nitidez las ventajas del tratamiento de reperfusión en cuanto a reducción de la morbimortalidad en una enfermedad tan prevalente en los países desarrollados. Si las diferentes opciones de reperfusión, farmacológica o mecánica, se aplican y especialmente si es precozmente desde el inicio de los síntomas, la mortalidad del infarto de miocardio puede ser inferior al 5%, cifra impensable hace tan sólo unos años. La intervención coronaria percutánea primaria es el método de reperfusión ideal. Sin embargo, desde una visión comunitaria y a la vista de la extensión del territorio y los tiempos de acceso desde el inicio de los síntomas al contacto con el sistema sanitario, así como al centro intervencionista, la reperfusión farmacológica y el traslado simultáneo para realizar intervención coronaria percutánea de rescate, si procediera, pueden ser una opción complementaria, con resultados no inferiores a los de la intervención coronaria percutánea primaria, en caso de que se la considerara como única opción. Navarra es una comunidad relativamente extensa (10.391 km2), con tres centros hospitalarios públicos: un centro con unidad coronaria y cardiología intervencionista, en el Complejo Hospitalario de Navarra en Pamplona, y dos hospitales comarcales, Estella y Tudela, ubicados a 50 y 90 km del centro intervencionista. Estratégicamente, el objetivo es reperfundir al mayor número de pacientes que presenten un infarto de miocardio con elevación del ST. Si es en el área de Pamplona-Pamplona Norte, siempre intervención coronaria percutánea primaria; si es en los dependientes de los hospitales comarcales de Estella y Tudela, estrategia invasiva o farmacoinvasiva en función de la suma de tiempos desde el inicio de los síntomas hasta el contacto con el sistema sanitario, más el tiempo teórico de traslado al centro intervencionista de Pamplona. Este tipo de estrategia combinada, con protocolos bien definidos, en una comunidad como la de Navarra, con peculiaridades urbanas y rurales, se muestra muy eficiente y su modelo, dentro de las dificultades, es de aplicación sencilla. The treatment of acute myocardial infarction has advanced considerably over the last three decades. Today, the benefits of reperfusion therapy are abundantly clear: it can reduce morbidity and mortality in a disease that has a very high prevalence in developed countries. If the various reperfusion treatments are used early after symptom onset, mortality due to myocardial infarction may be less than 5%, a level that was unthinkable just a few years ago. Primary percutaneous coronary intervention is the ideal reperfusion method. However, for the community as a whole in a region where distances are large and there may be a lengthy delay between symptom onset and hospital admission, pharmacological reperfusion with simultaneous transport for rescue percutaneous coronary intervention, if warranted, may be an alternative, and outcomes are not inferior to those of primary percutaneous coronary intervention when this is the only option. In the region of Navarre in Spain, a relatively extensive area (i.e. 10 391 km2) is covered by three public hospitals: the Complejo Hospitalario de Navarra in Pamplona and two district hospitals in Estella and Tudela, located 50 km and 90 km, respectively, from the interventional cardiology service in Pamplona. Strategically, the goal is to provide reperfusion therapy for the maximum possible number of patients with ST-elevation myocardial infarction. Primary percutaneous coronary intervention is always performed in patients from the area around Pamplona and North Pamplona. In areas served by the district hospitals in Estella and Tudela, either invasive treatment or the combination of pharmacological and invasive therapy may be used depending on the sum total of the time between symptom onset and first contact with the health system plus the theoretical transfer time to the interventional cardiology service in Pamplona. The use of this combination treatment strategy, based on well-defined protocols, in a region like Navarre, which is characterized a mixture of urban and rural communities, appears to be very effective and, within its limitations, the program was simple to implement.

Hospital mortality trend analysis of patients with ST elevation myocardial infarction in the Belgrade area coronary care units

Mortality in ST elevation myocardial infarction (STEMI) ranges from 4-24% and is dependent on the variety of patients' clinical characteristics (CC) that are present prior to and within the first hours of the onset of MI, affecting reliability of the diagnosis. The higher mortality rate of patients with STEMI should be associated with a higher rate of applied reperfusion therapy according to guidelines and randomized study results, which is in opposition to everyday hospital practice. The aim of this study was to analyze the mortality of STEMI patients in relationship to their clinical characteristics at presentation, their age, sex, risk factors, prior coronary disease, and time interval from symptom onset to hospital presentation, complications and administered therapy. The analysis involved patients treated in five coronary care units, four Belgrade Hospital Centres and the Belgrade Emergency Centre of the Clinical Centre of Serbia. Evaluated data was obtained from the Serbian National Registry for Acute Coronary Syndrome (REAKSS) and databases of local coronary care units (CCU). During 2005 and 2006, a total of 2739 patients with STEMI, of average age 63.3 +/- 11.7, with 64.9% males aged 61.3 +/- 11.7 and 35.1% females aged 67.0 +/- 10.7 (p < 0.01) who underwent treatment. Most of the patients (80.5%) were distributed within the elderly groups of 60, 70 and 80 years of age, with the highest percent of mortality rate (45.9%) noted at age 80 years. Anterior localization of myocardial infarction was observed in 40.2% of patients, with lethal outcome in 21.4% patients, while 59.8% of patients suffered inferiorly localized MI with much lower mortality rate (12.2%, p < 0.01). In 2005, STEMI was registered in 48.7%, while in 2006 in 44.7% of patients. Prior angina pectoris was present in 19.9% of patients, more frequently among women (p < 0.05), prior MI in 14.5% of patients, more often among males (p < 0.05), while aortocoronary revascularization was found in 3.9% of patients. Hospital mortality rate due to STEMI was higher in the group of patients with a history of prior MI (19.1% vs. 15.7%; p > 0.05). Regarding risk factors, hypertension was present in 61.8% of patients, more often among women (69.1% vs.57.9%) (p < 0.01), carrying a higher mortality rate of 18.9% vs. 9.9% among males (p < 0.01). Hyperlipidemia was found in 31.9% of patients; more frequently among women 34.8% vs. 30.4% males (p < 0.05), as well as diabetes mellitus observed in 25.1% of patients; 22.4% males and 30.1% females (p < 0.01). 39.6% of patients were smokers; 46.9% males and 28.0% females (p < 0.01). Heart failure had 33.4% of patients; mortality rate was registered in 28.2% of patients, and was significantly higher than in the non heart failure group (7.9%, p < 0.01). Heart rhythm disorders were registered in 21.3% of patients, more frequently involving posterior MI 55.3% vs 44.7% of anterior MI (p > 0.05), and was significantly higher among females 23.5% vs. 20.1% in males (p < 0.05). In 2005 in Belgrade hospitals, reperfusion therapy (RT) was performed in 34.6% of patients, mostly as thrombolytic therapy (TT) (in 99.0% of patients), and as percutaneous coronary intervention (PCI) in 1.0% of patients. STEMI mortality rate was 12.8%. In 2006, in the CCU of the In the Emergency Center RT was applied in 48.0% of patients, TT in 13.8% and PCI in 34.2%, while classical therapy without RT was applied in 52.0% of patients. Clinical characteristics significantly influence mortality in STEMI; a significantly higher mortality is among women, patients in their 80's and 90's, anterior MI localization and prior coronary disease. RT significantly lowers mortality in STEMI compared to the use of classical therapeutic approach and therefore STEMI patients with a higher mortality determined by their prehospital charactheristics, i.e. higher risk, are those who have higher benefit of RT, which should be taken into consideration when making decision about the therapy of choice.

Late medical versus interventional therapy for stable ST-segment elevation myocardial infarction

ST-segment elevation myocardial infarction (STEMI) is associated with high morbidity and mortality, but timely reperfusion is known to result in dramatically improved patient outcomes. As many as 40% of patients with STEMI, however, present late after symptom onset, which reduces the likelihood of them receiving reperfusion therapy. The past two decades have been plagued with controversy regarding the relative benefits of reperfusion therapy after 12 h from symptom onset. Despite considerable data supporting late reperfusion and the 'late open-artery hypothesis', recent studies have demonstrated a lack of benefit with late reperfusion. Moreover, advances in the medical management of STEMI have dramatically reduced morbidity and mortality, further challenging the need for more-invasive techniques. Numerous questions have arisen regarding the appropriate management and risk stratification of asymptomatic post-STEMI patients who present late after symptom onset. In light of recent data, we present a Review of late reperfusion in STEMI, specifically highlighting the effects of current medical therapies, risk-stratification techniques, and indications for the use of late reperfusion over medical management.

Special issues when caring for the older person with acute coronary syndromes

Persons 75 years of age or older constitute 6% of the US population but account for more than one third of those with acute coronary syndromes (ACS). Unfortunately, most randomized clinical trials have enrolled few older persons, and, as a result, few data are available to guide clinical practice. As in younger patients, aspirin, beta-blockers, nitrates, clopidogrel, heparin, statins, and angiotensin-converting enzyme inhibitors are useful, beginning with lower doses and carefully observing the patient for symptoms of toxicity. Similarly, older patients should not be denied the benefit of reperfusion therapy and early invasive strategy because of their age. Although primary angioplasty is an optimal reperfusion strategy, thrombolytic therapy is a beneficial alternative in carefully selected older patients. Although glycoprotein IIb/IIIa inhibitors appear to be beneficial in select cases, bleeding concerns exist. Despite a growing body of evidence in support of aggressive ACS care in older persons, evidence-based therapy is underused in older patients. Continued efforts are required to improve the quality of care to this high-risk cohort of ACS patients.