Albert J. H. Suurmeijer

Thrombus aspiration during primary percutaneous coronary intervention.

BACKGROUND Primary percutaneous coronary intervention (PCI) is effective in opening the infarct-related artery in patients with myocardial infarction with ST-segment elevation. However, the embolization of atherothrombotic debris induces microvascular obstruction and diminishes myocardial reperfusion. METHODS We performed a randomized trial assessing whether manual aspiration was superior to conventional treatment during primary PCI. A total of 1071 patients were randomly assigned to the thrombus-aspiration group or the conventional-PCI group before undergoing coronary angiography. Aspiration was considered to be successful if there was histopathological evidence of atherothrombotic material. We assessed angiographic and electrocardiographic signs of myocardial reperfusion, as well as clinical outcome. The primary end point was a myocardial blush grade of 0 or 1 (defined as absent or minimal myocardial reperfusion, respectively). RESULTS A myocardial blush grade of 0 or 1 occurred in 17.1% of the patients in the thrombus-aspiration group and in 26.3% of those in the conventional-PCI group (P<0.001). Complete resolution of ST-segment elevation occurred in 56.6% and 44.2% of patients, respectively (P<0.001). The benefit did not show heterogeneity among the baseline levels of the prespecified covariates. At 30 days, the rate of death in patients with a myocardial blush grade of 0 or 1, 2, and 3 was 5.2%, 2.9%, and 1.0%, respectively (P=0.003), and the rate of adverse events was 14.1%, 8.8%, and 4.2%, respectively (P<0.001). Histopathological examination confirmed successful aspiration in 72.9% of patients. CONCLUSIONS Thrombus aspiration is applicable in a large majority of patients with myocardial infarction with ST-segment elevation, and it results in better reperfusion and clinical outcomes than conventional PCI, irrespective of clinical and angiographic characteristics at baseline. (Current Controlled Trials number, ISRCTN16716833.)

Cardiac death and reinfarction after 1 year in the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS): a 1-year follow-up study

BACKGROUND Percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction can be complicated by spontaneous or angioplasty-induced embolisation of atherothrombotic material. Distal blockage induces microvascular obstruction and can result in less than optimum reperfusion of viable myocardium. The Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS) found that thrombus aspiration resulted in improved myocardial reperfusion compared with conventional PCI, but whether this benefit improves clinical outcome is unknown. We aimed to investigate whether the early efficacy of thrombus aspiration seen in TAPAS translated into clinical benefit after 1 year. METHODS Patients with ST-elevation myocardial infarction enrolled at the University Medical Centre Groningen were randomly assigned in a 1:1 ratio to either thrombus aspiration or conventional treatment, before undergoing initial coronary angiography. Exclusion criteria were rescue PCI after thrombolysis and known existence of a concomitant disease with life expectancy less than 6 months. Of the 1071 patients enrolled between January, 2005, and December, 2006, vital status at or beyond 1 year after randomisation was available for 1060 (99%). The primary endpoint was cardiac death or non-fatal reinfarction after 1 year, and analysis was by intention to treat. The TAPAS trial is registered with Current Controlled Trials number ISRCTN16716833. FINDINGS Cardiac death at 1 year was 3.6% (19 of 535 patients) in the thrombus aspiration group and 6.7% (36 of 536) in the conventional PCI group (hazard ratio [HR] 1.93; 95% CI 1.11-3.37; p=0.020). 1-year cardiac death or non-fatal reinfarction occurred in 5.6% (30 of 535) of patients in the thrombus aspiration group and 9.9% (53 of 536) of patients in the conventional PCI group (HR 1.81; 95% CI 1.16-2.84; p=0.009). INTERPRETATION Compared with conventional PCI, thrombus aspiration before stenting of the infarcted artery seems to improve the 1-year clinical outcome after PCI for ST-elevation myocardial infarction.

Angiotensin-(1–7) Attenuates the Development of Heart Failure After Myocardial Infarction in Rats

Background—The renin-angiotensin system (RAS) is a key player in the progression of heart failure. Angiotensin-(1–7) is thought to modulate the activity of the RAS. Furthermore, this peptide may play a part in the beneficial effects of angiotensin-converting enzyme inhibitors in cardiovascular disease. We assessed the effects of angiotensin-(1–7) on the progression of heart failure. Methods and Results—Male Sprague-Dawley rats underwent either coronary ligation or sham surgery. Two weeks after induction of myocardial infarction, intravenous infusion of angiotensin-(1–7) (24 &mgr;g/kg per hour) or saline was started by minipump. After 8 weeks of treatment, hemodynamic parameters were measured, endothelial function was assessed in isolated aortic rings, and plasma angiotensin-(1–7) levels were determined. Myocardial infarction resulted in a significant deterioration of left ventricular systolic and diastolic pressure, dP/dt, and coronary flow. Raising plasma levels 40-fold, angiotensin-(1–7) infusion attenuated this impairment to a nonsignificant level, markedly illustrated by a 40% reduction in left ventricular end-diastolic pressure. Furthermore, angiotensin-(1–7) completely preserved aortic endothelial function, whereas endothelium-dependent relaxation in aortas of saline-treated infarcted rats was significantly decreased. Conclusions—Angiotensin-(1–7) preserved cardiac function, coronary perfusion, and aortic endothelial function in a rat model for heart failure.

[18F]FLT-PET in oncology: current status and opportunities

In recent years, [18F]-fluoro-3′-deoxy-3′-L-fluorothymidine ([18F]FLT) has been developed as a proliferation tracer. Imaging and measurement of proliferation with PET could provide us with a non-invasive staging tool and a tool to monitor the response to anticancer treatment. In this review, the basis of [18F]FLT as a proliferation tracer is discussed. Furthermore, an overview of the current status of [18F]FLT-PET research is given. The results of this research show that although [18F]FLT is a tracer that visualises cellular proliferation, it also has certain limitations. In comparison with the most widely used PET tracer, [18F]FDG, [18F]FLT uptake is lower in most cases. Furthermore, [18F]FLT uptake does not always reflect the tumour cell proliferation rate, for example during or shortly after certain chemotherapy regimens. The opportunities provided by, and the limitations of, [18F]FLT as a proliferation tracer are addressed in this review, and directions are given for further research, taking into account the strong and weak points of the new tracer.

Timing of erythropoietin treatment for cardioprotection in ischemia/reperfusion

Erythropoietin (EPO) is a hormone known to stimulate hematopoiesis. However, recent research suggests additional properties of EPO, such as protection against ischemia/reperfusion (I/R) injury in various tissues. We studied the effect of timing of EPO administration on cardioprotection during I/R in the heart. Male Sprague–Dawley rats were subjected to 45 minutes of coronary occlusion, followed by 24 hours of reperfusion. Animals were randomized to receive saline or single dose of EPO (5000 IU/kg) either 2 hours before I/R, at the start of ischemia, or after the onset of reperfusion. The ratio of infarct area/area at risk (planimetry), left ventricular (LV) function (pressure development), and apoptosis (number of active caspase-3 positive cells) were determined after 24-hour reperfusion. Administration of EPO during different time points resulted in a 19 to 23% (P < 0.05) reduction in the infarct area/area at risk, which was accompanied by a trend toward better LV hemodynamic parameters. Apoptosis was significantly attenuated in groups treated with EPO at the start of ischemia (29% reduction) and after the onset of reperfusion (38%), and to a lesser extent (16%) in the group pre-treated with EPO. Thus, in vivo administration of EPO at different time points protects the myocardial structure and preserves cardiac function during I/R. Cardioprotective effect of EPO is associated with inhibition of apoptosis.

Value of P-glycoprotein, glutathione S-transferase pi, c-erbB-2, and p53 as prognostic factors in ovarian carcinomas.

PURPOSE To determine the prognostic value of immunostaining of P-glycoprotein (P-gp), glutathione S-transferase (GST) pi, c-erbB-2, and p53 in patients with advanced-stage ovarian carcinoma. PATIENTS AND METHODS Immunostaining of P-gp, GST pi, c-erbB-2, and p53 was performed on 89 primary tumors and 38 residual tumors after chemotherapy (P-gp and GST pi) in patients with advanced ovarian carcinoma treated with platinum- and doxorubicin-containing chemotherapy. The results of immunostaining were related to clinicopathologic prognostic factors, response to chemotherapy, and progression-free survival (PFS) and overall survival. RESULTS P-gp and GST pi immunoreactivity were present in 13 (15%) and 79 cases (89%), respectively, and were not associated with any other prognostic factor or PFS or overall survival. C-erbB-2 immunoreactivity was present in 18 cases (20%) and was associated with undifferentiated histiotype (P < .05), but not with PFS or overall survival. p53 immunoreactivity was present in the nuclei of 31 cases (35%) and cytoplasm of nine cases (10%). Nuclear p53 staining was associated with grade III tumors, presence of more than 1-L ascites, and residual tumor after first laparotomy more than 2 cm. Nuclear p53 staining was associated with shorter PFS (relative risk [RR], 3.3; 95% confidence interval [CI], 2.0 to 5.6) and overall survival (RR, 2.6; 95% CI, 1.7 to 3.8). After adjustment for presence of more than 1-L ascites or age more than 50 years, nuclear p53 staining did not retain independent prognostic significance in stage III/IV tumors. The frequency of P-gp staining in residual tumors after chemotherapy (18 of 38 cases) was higher in comparison to untreated tumors (13 of 89 cases) (P < .001). No combination of prognostic parameters was able to predict response to chemotherapy adequately. CONCLUSION Nuclear immunoreactivity of p53 in ovarian carcinomas is associated with shorter PFS and overall survival and determinants of more aggressive tumor growth. The higher frequency of P-gp immunoreactivity in residual tumors after chemotherapy points to induction of P-gp in ovarian carcinomas by doxorubicin-containing combination chemotherapy. The determination of P-gp, GST pi, c-erbB-2, and p53 does not permit more adequate prediction of response to chemotherapy.

Phospholamban R14del mutation in patients diagnosed with dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy: evidence supporting the concept of arrhythmogenic cardiomyopathy

To investigate whether phospholamban gene (PLN) mutations underlie patients diagnosed with either arrhythmogenic right ventricular cardiomyopathy (ARVC) or idiopathic dilated cardiomyopathy (DCM).

The insulin-like growth factor system and sarcomas†

Sarcomas are a diverse group of malignant mesenchymal tumours arising from bone and soft tissues. The identification of critical cellular signalling pathways in sarcomas is an important issue for the development of new targeted therapies. This review highlights the experimental and clinical evidence supporting the role of the insulin‐like growth factor (IGF) signalling system in the cellular transformation and progression of several types of sarcoma, including rhabdomyosarcoma, synovial sarcoma, leiomyosarcoma, Ewings sarcoma and osteosarcoma. Preclinical data suggest that the IGF system could be a promising target for therapy in these sarcomas. Currently, therapies interrupting IGF signalling have been or are being developed. In recent phase 1 clinical studies with humanized monoclonal antibodies directed against IGF receptor type 1 (IGF‐1R), objective tumour responses were observed in several patients with Ewings sarcoma, encouraging further clinical testing in Ewings sarcoma and other sarcoma (sub)types. Moreover, the occasional occurrence of paraneoplastic hypoglycaemia as a result of the secretion of incompletely processed forms of pro‐IGF‐II by sarcomas is discussed. Copyright

Erythropoietin improves left ventricular function and coronary flow in an experimental model of ischemia-reperfusion injury†

Recent studies show that erythropoietin (EPO) plays a protective role in brain ischemia. In this condition, administration of EPO protects neurons from ischemic damage. Recently, it has been shown that in patients with chronic heart failure (CHF), EPO treatment improved cardiac function. In the present study we assessed the role of EPO and EPO‐receptor (EPO‐R) in the heart.

Incidence and clinical consequences of distal embolization on the coronary angiogram after percutaneous coronary intervention for ST-elevation myocardial infarction

AIMS We investigated the incidence and sequelae of angiographically visible distal embolization (AVDE) after primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction patients treated with aspirin, heparin, clopidogrel, and glycoprotein-IIb/IIIa inhibitors. METHODS AND RESULTS As part of TAPAS, AVDE was a predefined secondary endpoint. We compared angiographic and clinical characteristics, and outcomes of patients with and without AVDE after PCI. AVDE was present on 6.3% of 883 post-procedural angiograms. Angiographically visible distal embolization was associated with significantly worse outcomes, as expressed by lower myocardial blush grade, impaired ST-segment resolution, and higher enzyme levels (all P </= 0.001). Mortality 1 year after PCI was 4 of 56 (7.1%) in patients with AVDE and 43 of 827 (5.2%) in patients without AVDE (P= ns), re-infarction occurred in 5 of 56 (8.9%), and 25 of 827 (3.0%) patients (P = 0.018). The thrombus aspirate more often contained erythrocytes in patients with AVDE than in patients without AVDE (50.0% vs. 15.7%, P < 0.001), and the size of the aspirated thrombus was larger in patients with AVDE (P = 0.002). CONCLUSION In patients with triple anti-platelet therapy, the incidence of AVDE after PCI is low, compared with previous reports. Nevertheless, AVDE is associated with impaired myocardial reperfusion and poor outcome. Thrombus composition and size are related to AVDE after PCI.