Late Thrombolysis Research Articles

Nebulization of Low-Dose S-Nitrosoglutathione in Diabetic Stroke Enhances Benefits of Reperfusion and Prevents Post-Thrombolysis Hemorrhage

The COVID-19 pandemic has escalated the occurrence of hypoxia including thrombotic stroke worldwide, for which nitric oxide (NO) therapy seems very promising and translatable. Therefore, various modes/routes of NO-delivery are now being tested in different clinical trials for safer, faster, and more effective interventions against ischemic insults. Intravenous (IV) infusion of S-Nitrosoglutathione (GSNO), the major endogenous molecular pool of NO, has been reported to protect against mechanical cerebral ischemia-reperfusion (IR); however, it has been never tested in any kind of “clinically” relevant thromboembolic stroke models with or without comorbidities and in combination with the thrombolytic reperfusion therapy. Moreover, “IV-effects” of higher dose of GSNO following IR-injury have been contradicted to augment stroke injury. Herein, we tested the hypothesis that nebulization of low-dose GSNO will not alter blood pressure (BP) and will mitigate stroke injury in diabetic mice via enhanced cerebral blood flow (CBF) and brain tissue oxygenation (PbtO2). GSNO-nebulization (200 μg/kgbwt) did not alter BP, but augmented the restoration of CBF, improved behavioral outcomes and reduced stroke injury. Moreover, GSNO-nebulization increased early reoxygenation of brain tissue/PbtO2 as measured at 6.5 h post-stroke following thrombolytic reperfusion, and enervated unwanted effects of late thrombolysis in diabetic stroke. We conclude that the GSNO-nebulization is safe and effective for enhancing collateral microvascular perfusion in the early hours following stroke. Hence, nebulized-GSNO therapy has the potential to be developed and translated into an affordable field therapy against ischemic events including strokes, particularly in developing countries with limited healthcare infrastructure.

Is late thrombolysis effective for subacute renal vein thrombosis in patients with nephrotic syndrome? a case report

Renal vein thrombosis (RVT) associated with nephrotic syndrome (NS) in patients with flank pain is rarely the earliest manifestation. Despite the absence of formal guidelines, treatment generally consists of prophylaxis against new thrombotic events and clot dissolution (thrombolysis) or clot removal (thrombectomy). We describe the case of a 25-year-old woman with lumbar pain, nausea and vomiting, who developed nephrotic proteinuria, macroscopic hematuria and loss of renal function requiring hemodialysis without improvement with methylprednisolone and cyclophosphamide. Considered diagnoses of systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APS). Angiotomography showed subacute vena cava thrombosis with extension to the two renal veins. Alteplase thrombolysis was performed to recovery of renal function. Patient progressed with improvement of renal function and discontinuation of hemodialysis. In conclusion, late thrombolysis may be effective for subacute RVT in NS patients.

Progressive ischaemic stroke: the difficulty in choosing antithrombotic therapy

Progressive ischaemic stroke is a clinical form of unfavourable progression of an acute cerebrovascular accident, found in around 20% of cases during the acute period. The strategy and approach to managing patients with an apparent deterioration during the acute period of stroke have not been fully established. Various types of antithrombotic therapy are discussed in the literature, with the use of antiplatelet drugs considered the most promising. The authors analyse all types of antithrombotic therapy for progressive ischaemic stroke and examine in detail the only known case of late thrombolysis, which was performed in 1968.

Whole body hypothermia extends tissue plasminogen activator treatment window in the rat model of embolic stroke

Late treatment with tissue plasminogen activator (tPA) leads to reperfusion injury and poor outcome in ischemic stroke. We have recently shown the beneficial effects of local brain hypothermia after late thrombolysis. Herein, we investigated whether transient whole-body hypothermia was neuroprotective and could prevent the side effects of late tPA therapy at 5.5 h after embolic stroke. After induction of stroke, male rats were randomly assigned into four groups: Control, Hypothermia, tPA and Hypothermia+tPA. Hypothermia started at 5 h after embolic stroke and continued for 1 h. Thirty min after hypothermia, tPA was administrated. Infarct volume, brain edema, blood-brain barrier (BBB) and matrix metalloproteinase-9 (MMP-9) were assessed 48 h and neurological functions were assessed 24 and 48 hour post-stroke. Compared with the control or tPA groups, whole-body hypothermia decreased infarct volume (P < 0.01), BBB disruption (P < 0.05) and MMP-9 level (P < 0.05). However, compared with hypothermia alone a combination of hypothermia and tPA was more effective in reducing infarct volume. While hypothermia alone did not show any effect, its combination with tPA reduced brain edema (P < 0.05). Hypothermia alone or when combined with tPA decreased MMP-9 compared with control or tPA groups (P < 0.01). Although delayed tPA therapy exacerbated BBB integrity, general cooling hampered its leakage after late thrombolysis (P < 0.05). Moreover, only combination therapy significantly improved sensorimotor function as well as forelimb muscle strength at 24 or 48 h after stroke (P < 0.01). Transient whole-body hypothermia in combination with delayed thrombolysis therapy shows more neuroprotection and extends therapeutic time window of tPA up to 5.5 h.

Late thrombolysis for stroke works, but how do we do it?

Late thrombolysis for stroke works, but how do we do it?

Microglial-mediated PDGF-CC activation increases cerebrovascular permeability during ischemic stroke

Treatment of acute ischemic stroke with the thrombolytic tissue plasminogen activator (tPA) can significantly improve neurological outcomes; however, thrombolytic therapy is associated with an increased risk of intra-cerebral hemorrhage (ICH). Previously, we demonstrated that during stroke tPA acting on the parenchymal side of the neurovascular unit (NVU) can increase blood–brain barrier (BBB) permeability and ICH through activation of latent platelet-derived growth factor-CC (PDGF-CC) and signaling by the PDGF receptor-α (PDGFRα). However, in vitro, activation of PDGF-CC by tPA is very inefficient and the mechanism of PDGF-CC activation in the NVU is not known. Here, we show that the integrin Mac-1, expressed on brain microglia/macrophages (denoted microglia throughout), acts together with the endocytic receptor LRP1 in the NVU to promote tPA-mediated activation of PDGF-CC. Mac-1-deficient mice (Mac-1−/−) are protected from tPA-induced BBB permeability but not from permeability induced by intracerebroventricular injection of active PDGF-CC. Immunofluorescence analysis demonstrates that Mac-1, LRP1, and the PDGFRα all localize to the NVU of arterioles, and following middle cerebral artery occlusion (MCAO) Mac-1−/− mice show significantly less PDGFRα phosphorylation, BBB permeability, and infarct volume compared to wild-type mice. Bone-marrow transplantation studies indicate that resident CD11b+ cells, but not bone-marrow-derived leukocytes, mediate the early activation of PDGF-CC by tPA after MCAO. Finally, using a model of thrombotic stroke with late thrombolysis, we show that wild-type mice have an increased incidence of spontaneous ICH following thrombolysis with tPA 5 h after MCAO, whereas Mac-1−/− mice are resistant to the development of ICH even with late tPA treatment. Together, these results indicate that Mac-1 and LRP1 act as co-factors for the activation of PDGF-CC by tPA in the NVU, and suggest a novel mechanism for tightly regulating PDGFRα signaling in the NVU and controlling BBB permeability.

Effect of thrombolytic therapy on the patterns of post myocardial infarction ventricular septal rupture

ObjectivesVentricular septal rupture (VSR) is a rare but feared complication after myocardial infarction (MI). The objective of this study was to investigate the effects of thrombolytic therapy on the patterns of VSR following MI. Methods30 consecutive patients admitted to a single tertiary level cardiac hospital with a diagnosis of acute MI and developed VSR in the hospital were included. The effect on thrombolytic therapy on the formation of VSR and its clinical outcome was studied. ResultsOut of 30 patients, 15 patients received thrombolytic therapy.10 received early (<12h) and 5 received late (>12h). The median time to post MI VSR formation was significantly shorter in thrombolysis group compared to non thrombolysis group at 1 vs 3 days(p=0.026). The median time for VSR formation was shorter in early thrombolysis group compared to late thrombolysis group at 1 vs 3 days (p=0.022). There was no difference between late and no thrombolytic therapy (3 vs 3 days, p=0.672). There was no significant difference in the mortality between thrombolytic and no thrombolytic therapy (p=0.690). Patients treated medically had a significant higher mortality compared to patients treated surgically (p=0.005). ConclusionThrombolytic therapy results in an earlier presentation of VSR after MI. This earlier presentation may be due to reduction in the number of patients developing late VSR after thrombolytic therapy, while the number of patients developing an early VSR remaining unaffected. Despite improvements in medical therapy and percutaneous and surgical techniques, mortality with this complication remains extremely high.

Early versus late thrombolysis in acute arterial occlusion of lower extremity

BackgroundAcute arterial occlusion in lower extremity is an urgent condition which occurs when there is an abrupt interruption of blood flow into an extremity. Reperfusion through early intervention can increase limb salvage and decrease mortality. There was no common agreement when is the best to start thrombolysis in treating acute arterial occlusion. This study was designed to study the efficacy of an early thrombolysis compared with a late thrombolysis. MethodWe identified all patients discharged from the Gwangju Veterans hospital with a diagnosis of acute arterial occlusion between 2006 and 2014. 72 patients were eligible, and every patient had treated with catheter-directed thrombolysis on the day or 1day after admission. Among them, 42 patients had undergone an early thrombolysis (less than 7days after the onset of symptoms) and the other 30 patients had undergone a late thrombolysis (more than 7days after the onset of symptoms). The primary outcome was amputation rate at 6months. The secondary outcomes were all cause mortality at 6months and increase of ankle brachial index (ABI). ResultsAmputation rate at 180days in the early thrombolysis group was 7.1% as compared with 30% in the late thrombolysis group. All cause mortality at 6months and increase of ABI were not different between two groups. In multivariable Cox-regression analysis, late thrombolysis was independent predictor of amputation at 6months. ConclusionEarly thrombolysis was superior in preventing amputation than late thrombolysis.

Recruitment to trials of late thrombolysis: Lessons from the EXTEND study

To increase the percentage of acute stroke patients benefiting from thrombolysis, the utility of expanding the time window of treatment beyond 4.5hours after stroke onset needs to be investigated. We aimed to identify the target population and the challenges of recruitment of patients for the time window beyond 4.5hours. Extending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND), a multicentre randomised controlled trial testing the efficacy of thrombolytic therapy in patients with clinically significant ischaemic penumbra between 4.5 to 9hours after stroke onset, was used as a model to evaluate inclusion and exclusion criteria for late thrombolysis trials. Data from all stroke patients admitted to Austin Health over a 1year period were retrospectively analysed. Case notes were examined to determine potential trial eligibility. Of 556 patients assessed, 95 (17%) presented during the EXTEND time window. Sixty-seven of these (70.5%) were wake-up strokes (WUS) and 28 (29.5%) arrived between 4.5 and 9hours after symptoms onset. At least one exclusion criterion was found for 78 (82%) of them. Hence, 17 (3%) patients arrived within an appropriate time frame for the study without any exclusion criteria. Most of these (13) arrived outside routine MRI hours. The number of patients recruited would have increased more than three-fold if imaging had been available 24hours, 7days a week. A significant proportion (17%) of ischaemic stroke patients presented between 4.5 and 9hours after stroke onset. The majority of these were WUS. The major challenge identified for patient recruitment was imaging availability.

Comparison of early and late thrombolysis in patients with acute pulmonary embolism

Purpose: To compare the efficacy of thrombolytic therapy (TLT) in high risk patients with acute pulmonary embolism (APE) in the first day of onset of the disease and in patients with late hospitalization (3-10 days) Materials and methods: Retrospectively were processed 56 patients with a diagnosis of high risk APE (30 men, 26 women, age 60,43±3,03 years). Patients were divided into 2 groups: Group 1 includes 30 patients who were hospitalized for 1 day from an episode of APE. Group 2 includes 26 patients with APE from 3 to 10 day before hospitalization. Each group did not differ by sex, age, body weight, comorbidities. Patients of both groups after the diagnosis of high risk APE got TLT with Alteplaseof 100 mg (10 mg i/v bolus for 1 - 2 minutes, 90 mg i/v infusion over 2 hours). All patients received similar anticoagulant therapy. Patients of both groups were examined three times: before TLT (D 0), after infusion of Alteplase during 1st day (D 1) and at discharge (15±1,3 day, D 15). Results: In both groups increased SaO2, systolic blood pressure (SBP), and decreased pulmonary pressure (PP), right ventricular (RV) size and inferior vena cava (IVC) on D1 and D15 compared to D0 (all p<0,05). SaO2, RV, IVC, PP decreased significantly in Group 1 compared to patients in Group 2 on D1, this tendency continued to D15. All results see in the Table. View this table: Conclusion: The effectiveness of thrombolysis in patients of Group 1 was significantly better than in group 2. In the absence of clear criteria for the effectiveness of TLT in patients with high risk APE, the positive dynamics of RV function (size of RV, IVC, PP) and SaO2, remain simple and reliable criteria for evaluation of TLT in patients without invasive methods of treatment.

Immunotherapy for Stroke: A New Hope of Treatment (P07.004)

Objective: Tissue-type plasminogen activator (tPA, endogenous and exogenous) has two faces in acute ischemic stroke: beneficial fibrinolysis in the vascular bed, but damaging effects on the neurovascular unit and the brain parenchyma. To improve this profile, we used our knowledge of the underlying molecular (patho)physiology to develop a novel treatment strategy for stroke, relying on antibodies targeting the pro-neurotoxic effects of tPA. Background As the result of the occlusion of a cerebral artery by a blood clot. To date, the only clinical treatment is the use of tissular Plasminogen Activator (tPA, Actilyse®) for its fibrinolytic activity but with a certain risk of haemorrhagic transformation and of neurotoxicity through a modulation of NMDA receptors. The aim here was to validate a strategy of passive immunotherapy preventing the interaction of tPA with the NMDAr in a model of thromboembolic stroke with tPA-induced reperfusion in mice. Design/Methods: After production and characterization of antibodies (αATD-NR1) that specifically prevent the interaction of tPA with the ATD-NR1 of N-methyl-d-aspartate receptors, we have evaluated their efficacy in a model of murine thromboembolic stroke with or without recombinant tPA-induced reperfusion, coupled to MRI, near-infrared fluorescence imaging, and behavior assessments. Results: In vitro, αATD-NR1 prevented the proexcitotoxic effect of tPA without altering N-methyl-d-aspartate-induced neurotransmission. In vivo, based on a dedicated model of murine thrombo-embolic stroke, we demonstrate the efficiency of immunotherapy in a complete pre-clinical screen: after a single administration (alone or with late thrombolysis), antibodies dramatically reduce ischemic brain injuries, improve long-term neurological outcome and, in parallel, attenuate critical ischemic events including blood-brain barrier leakage and activation of MMP-3, MMP-9, and the PDGF-CC pathway. Conclusions: Thus, the prospect of this immunotherapy is an extension of the range of treatable patients, whether used as a monotherapy or, in combinations, to extend the therapeutic window for thrombolysis. Supported by: The INSERM, the French Ministry of Research and Technology, and the Eurostroke-Arise Program (FP7). Disclosure: Dr. Macrez has nothing to disclose. Dr. Defer has received personal compensation for activities with BiogenIdec, Novartis, Teva Pharmaceutical Industries Ltd, Merck Serono, and Guerbet. Dr. Vivien has nothing to disclose. Dr. Ali has nothing to disclose.

Late Thrombolysis in Massive Pulmonary Thromboembolism

Pulmonary thromboembolism (PTE) remains a diagnostic and therapeutic challenge for physicians. Anticoagulation with heparin remains as the cornerstone in its management, reserving thrombolysis for cases with hemodynamic impairment. The later has been associated with haemorrhagic complications and has proved beneficial when initiated within the first 48 hours of PTE; but there is little evidence supporting its use passed this time. We present a case of an 84 year old female admitted in our unit and treated successfully with thrombolysis for massive PTE at the fifth day of diagnosis. The patient improved towards complete recovery and was discharged from the hospital 22 days after admission without complications.

Selective inhibition of GluN2D-containing N-methyl-D-aspartate receptors prevents tissue plasminogen activator-promoted neurotoxicity both in vitro and in vivo

BackgroundTissue plasminogen activator (tPA) exerts multiple functions in the central nervous system, depending on the partner with which it interacts. In particular, tPA acts as a positive neuromodulator of N-methyl-D-aspartate glutamatergic receptors (NMDAR). At the molecular level, it has been proposed that the pro-neurotoxicity mediated by tPA might occur through extrasynaptic NMDAR containing the GluN2D subunit. Thus, selective antagonists targeting tPA/GluN2D-containing NMDAR signaling would be of interest to prevent noxious effects of tPA.ResultsHere, we compared three putative antagonists of GluN2D-containing NMDAR and we showed that the new compound UBP145 ((2R*,3S*)-1-(9-bromophenan-threne-3-carbonyl)piperazine-2,3-dicarboxylic acid) is far more selective for GluN2D subunits than memantine and PPDA (phenanthrene derivative (2S*, 3R*)-1-(phenanthrene-2-carbonyl)piperazine-2,3-dicarboxylic acid). Indeed, in vitro, in contrast to the two other compounds, UBP145 prevented NMDA toxicity only in neurons expressing GluN2D (ie, in cortical but not hippocampal neurons). Furthermore, in cultured cortical neurons, UBP145 fully prevented the pro-excitotoxic effect of tPA. In vivo, we showed that UBP145 potently prevented the noxious action of exogenous tPA on excitotoxic damages. Moreover, in a thrombotic stroke model in mice, administration of UBP145 prevented the deleterious effect of late thrombolysis by tPA.ConclusionsIn conclusion, tPA exerts noxious effects on neurons by acting on GluN2D-containing NMDAR and pharmacological antagonists of GluN2D-containing NMDAR could be used to prevent the ability of tPA to promote neurotoxicity.

Delay in Thrombolysis of Massive and Submassive Pulmonary Embolism

To report the time of delay in thrombolysis of massive and submassive pulmonary embolism (PE). We enrolled 83 consecutive patients with massive and submassive PE from 8 hospitals between June 2006 and March 2009. We recorded the delay between symptom onset and thrombolysis. The clinical findings related to early thrombolysis (delay ≤ 2 days) were analyzed. Median of the delay in thrombolysis was 8 days with 82% over 2 days, 53% over 7 days, and 6% over 25 days. Compared to the late thrombolysis (delay >2 days), patients with early thrombolysis more frequently had murmurs at the tricuspid area (26.7% vs 6.1%, P = .053), less frequently had cough (20% vs 59.7%, P = .005) and increased P2 (pulmonic component of second heart sound; 33.3% vs 61.2%, P = .049), and more patients were thrombolysed in off-hours (86.7% vs 57.4%, P = .034). The time of delay in thrombolysis is too long and the symptoms and signs between early and late thrombolysis groups may differ.

MRI May Help Identify Patients Who Can Benefit from Late Thrombolysis

MRI May Help Identify Patients Who Can Benefit from Late Thrombolysis

195: Causes of In-Hospital Delay for Door-to-Needle Times in Patients Presenting With Acute ST-Elevation Myocardial Infarct in Rural Malaysia

Study Objective: Background: In developing countries such as Malaysia, the primary mode for revascularization is via thrombolytic therapy. The Malaysian Clinical Practice Guideline on acute ST-elevation myocardial infarction advised the implementation of a 30-minute door-to-needle time. This study aims to evaluate the mean door-to-needle times and the reasons for in-hospital delays. Methods: Ninety four patients with acute ST elevation myocardial infarction patients were screened and 75 patients were recruited in this prospective observational study. The mean door-to-needle times were recorded and the reasons for delays in door-to-needle times were elucidated. Results: The majority of patients were male (89.3%), of Malay ethnicity (84%), presenting with anterior MI (69.3%) with a mean age of 57.0 � 9.52 years. The mean door-to-needle time was 80.54 � 84.8 minutes. Only 20% achieved the 30- minute door-to-needle time and only 65.3% achieved the 60 minute door-to-needle time. The reasons for late thrombolysis were quoted as late referrals from A�E (50%), hypertensive emergency (22%), resuscitation (17%) and others (11%). Conclusion: There is significant in-hospital delay in administrating thrombolytic agents for patients presenting with acute ST-elevation myocardial infarction. Some of the delays were unavoidable (hypertensive emergency and hypotension or VT/VF requiring resuscitation) but the majority of the delay is due to late referrals from A�E to attending cardiology on-call officers.

Spontaneous Late Thrombolysis of an Occluded Saphenous Vein Graft Subsequent to Acute Myocardial Infarction Treated with Percutaneous Coronary Intervention to the Native Culprit Vessel

A 67-year-old male with prior history of myocardial infarction and coronary artery bypass grafting (individual vein grafts to the left anterior descending artery [LAD] and right coronary artery) presented with an acute anterior ST elevation myocardial infarction and cardiogenic shock. The vein graft to the LAD was occluded with heavy thrombus burden and there was severe native CAD. Given the degree of thrombus burden and other anatomic considerations, percutaneous intervention with stenting was performed to the native proximal LAD. Three months later, after complaining of atypical chest pain, repeat angiogram revealed a spontaneous widely patent vein graft to the LAD and occluded proximal LAD.

Combination therapy of moderate hypothermia and thrombolysis in experimental thromboembolic stroke—An MRI study

Thrombolysis (T) is limited by reperfusion-associated injury and the short therapeutic window after stroke onset. The present study investigates whether hypothermia alone or in combination with thrombolysis has beneficial effects after experimental thromboembolic stroke. Wistar rats ( n = 60) were subjected to thromboembolic occlusion (TE) of the middle cerebral artery (MCA). Thrombolysis (T) was performed with intravenous recombinant tissue-plasminogen activator (rt-PA) 1 h (early T) or 3 h (late T) after TE. Hypothermia (Hy) was applied for 4 h at 33°C started 1 h after TE. Experimental groups included control (C), early thrombolysis (ET), late thrombolysis (LT), hypothermia (Hy), early thrombolysis plus hypothermia (ET+Hy), and late thrombolysis plus hypothermia (LT+Hy). Animals were investigated by MRI and silver infarct staining (SIS) to assess the cerebral infarct size. All animals of group Hy survived, in contrast to 40% in group C ( P < 0.05). ET+HY and LT+Hy showed a trend towards better survival as compared to ET and LT alone. PWI parameters were not significantly different between ET versus ET+HY and LT versus LT+Hy, but rt-PA administration led to improved cerebral perfusion in MRI. Significant differences in infarct volumes (T2/SIS) were found after 24 h in all treatment groups versus the control group ( P < 0.05). The lesion volume calculated from T2 was significantly smaller in ET (16% ± 5%), ET+Hy (10 ± 4%), and LT+Hy (20% ± 9%) after 5.5 h (10.8% ± 4.8%) versus C (42% ± 15%), ( P < 0.05). These data indicate that hypothermia improves survival and decreases infarct volume. However, there were no significant differences between the use of rt-PA alone or in combination with hypothermia. Further studies are needed to confirm these effects, also several days after stroke onset.

Arrhrythmias and haemodynamic effects associated with early versus late prehospital thrombolysis for acute myocardial infarction.

The occurrence of arrhythmias and haemodynamic changes was studied prospectively in 226 consecutive patients who received prehospital thrombolysis for acute ST-elevation myocardial infarction (STEMI) in two Helicopter Emergency Medical Service (HEMS) systems in Southern Finland. Of the 226 patients, 129 were classified as receiving early (pain to treatment-time <90 min) and 97 as late (pain to treatment-time >90 min) treatment. Data on all arrhythmias and haemodynamic disturbances during the prehospital phase were collected. Arrhythmias occurred in 39% of all patients (40% in the early and 38% in the late group). A third of the patients received treatment for their arrhythmia (38% in the early group and 24% in the late group, P = NS). The most common arrhythmia was ventricular extrasystoles, which did not require any treatment in the majority of patients. On arrival of the EMS crew, 14% of all patients were hypotensive (14% in the early and 13% in the late group). After thrombolytic treatment, 7% of all patients became hypotensive (7% of the patients in both groups). The most common treatment for hypotension was fluid administration. Of the 15 patients who received thrombolysis after cardiopulmonary resuscitation (CPR), four patients suffered from arrhythmias and six patients developed hypotension after initiation of thrombolytic treatment. Although arrhythmias and haemodynamic changes were frequent in the prehospital setting after initiation of thrombolytic therapy, severe adverse events were rare. Those requiring therapeutic measures responded well to treatment. The occurrence of events was not related to the timing of thrombolysis in relation to the duration of pain.

Late left ventricular pseudoaneurysm formation following subacute myocardial infarction

We describe a patient with a subacute inferior myocardial infarction who developed a pseudo–aneurysm more than 18 days after the acute event. This is an unusual case with three different complications of a myocardial infarction: Firstly, ventricular rupture is usually the result following transmural myocardial infarction without reperfusion. However, coronary angiography confirmed reperfusion after late thrombolysis in this patient. The subacute rupture could potentially be caused or aggravated by the late thrombolysis. Secondly, this patient developed a mural apical thrombus in a non-infarcted region. It seems most likely that the new infarct caused a low flow state which enhanced thrombus formation. Against expectations, this developed at the apex rather than the site of the recent inferior wall myocardial infarction. Thirdly, we documented the development of a pseudo–aneurysm more than 18 days after the myocardial infarction. This complication is rarely seen at this stage after a myocardial infarction, as most pseudo–aneurysms are formed within 7 days after a myocardial infarction. We have beautifully visualised the apical thrombus and pseudo–aneurysm with echocardiography. This report shows that serial echocardiography is a very useful tool in evaluating the patient's clinical and cardiac status in the period after a myocardial infarction.