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Biomedical subjects

M Vrolix

Publications and source records attributed to M Vrolix.

At least 19 recordsLinked to original sources

A synthetic factor-Xa inhibitor (ORG31540/SR9017A) as an adjunct to fibrinolysis in acute myocardial infarction. The PENTALYSE study.

BACKGROUND: ORG31540/SR90107A, a synthetic pentasaccharide, is a selective inhibitor of factor-Xa. It was hypothesized that prolonged factor-Xa inhibition with pentasaccharide may be an effective and safe antithrombotic co-therapy in acute myocardial infarction. METHODS AND RESULTS: Patients (n=333) with evolving ST-segment elevation acute myocardial infarction were treated with aspirin and alteplase and randomized to unfractionated heparin, given intravenously during 48 to 72 h, or to a low, medium or high dose of pentasaccharide, administered daily for 5 to 7 days, intravenously on the first day, then subcutaneously. Coronary angiography was performed at 90 min and on days 5 to 7. Thrombolysis in Myocardial Infarction (TIMI) flow grade 3 rates at 90 min were similar in the four treatment groups. Among patients with TIMI 3 flow at 90 min and who did not undergo a coronary intervention (n=155), a trend towards less reocclusion of the infarct-related vessel on days 5 to 7 was observed with pentasaccharide: 0.9% vs 7.0% with unfractionated heparin (P=0.065). Also, fewer revascularizations during the 30-day follow-up period were performed in patients given pentasaccharide (39% vs 51% for unfractionated heparin;P=0.054). The primary safety end-point, the combined incidence of intracranial haemorrhage and need for blood transfusion, was identical with pentasaccharide and unfractionated heparin (7.1%). One non-fatal intracranial haemorrhage occurred in the 241 patients given pentasaccharide (0.4%). CONCLUSIONS: In this study, pentasaccharide given together with alteplase was safe and as effective as unfractionated heparin in restoring coronary artery patency. Prolonged administration of pentasaccharide was associated with a trend towards less reocclusion and fewer revascularizations. Selective factor-Xa-inhibition seems to be an attractive therapeutic concept in patients presenting with ST-segment elevation acute myocardial infarction.

Adult↗

A randomized placebo-controlled trial of fluvastatin for prevention of restenosis after successful coronary balloon angioplasty; final results of the fluvastatin angiographic restenosis (FLARE) trial.

BACKGROUND: The 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors competitively inhibit biosynthesis of mevalonate, a precursor of non-sterol compounds involved in cell proliferation. Experimental evidence suggests that fluvastatin may, independent of any lipid lowering action, exert a greater direct inhibitory effect on proliferating vascular myocytes than other statins. The FLARE (Fluvastatin Angioplasty Restenosis) Trial was conceived to evaluate the ability of fluvastatin 40 mg twice daily to reduce restenosis after successful coronary balloon angioplasty (PTCA). METHODS: Patients were randomized to either placebo or fluvastatin 40 mg twice daily beginning 2-4 weeks prior to planned PTCA and continuing after a successful PTCA (without the use of a stent), to follow-up angiography at 26+/-2 weeks. Clinical follow-up was completed at 40 weeks. The primary end-point was angiographic restenosis, measured by quantitative coronary angiography at a core laboratory, as the loss in minimal luminal diameter during follow-up. Clinical end-points were death, myocardial infarction, coronary artery bypass graft surgery or re-intervention, up to 40 weeks after PTCA. RESULTS: Of 1054 patients randomized, 526 were allocated to fluvastatin and 528 to placebo. Among these, 409 in the fluvastatin group and 427 in the placebo group were included in the intention-to-treat analysis, having undergone a successful PTCA after a minimum of 2 weeks of pre-treatment. At the time of PTCA, fluvastatin had reduced LDL cholesterol by 37% and this was maintained at 33% at 26 weeks. There was no difference in the primary end-point between the treatment groups (fluvastatin 0.23+/-0.49 mm vs placebo 0.23+/-0.52 mm, P=0.95) or in the angiographic restenosis rate (fluvastatin 28%, placebo 31%, chi-square P=0.42), or in the incidence of the composite clinical end-point at 40 weeks (22.4% vs 23.3%; logrank P=0.74). However, a significantly lower incidence of total death and myocardial infarction was observed in six patients (1.4%) in the fluvastatin group and 17 (4.0%) in the placebo group (log rank P=0.025). CONCLUSION: Treatment with fluvastatin 80 mg daily did not affect the process of restenosis and is therefore not indicated for this purpose. However, the observed reduction in mortality and myocardial infarction 40 weeks after PTCA in the fluvastatin treated group has not been previously reported with statin therapy. Accordingly, a priori investigation of this finding is indicated and a new clinical trial with this intention is already underway.

Angioplasty, Balloon, Coronary↗

Randomized multicenter comparison of conventional anticoagulation versus antiplatelet therapy in unplanned and elective coronary stenting. The full anticoagulation versus aspirin and ticlopidine (fantastic) study.

BACKGROUND: Dual therapy with ticlopidine and aspirin has been shown to be as effective as or more effective than conventional anticoagulation in patients with an optimal result after implantation of intracoronary metallic stents. However, the safety and efficacy of antiplatelet therapy alone in an unselected population has not been evaluated. METHODS: Patients were randomized to conventional anticoagulation or to treatment with antiplatelet therapy alone. Indications for stenting were classified as elective (decided before the procedure) or unplanned (to salvage failed angioplasty or to optimize the results of balloon angioplasty). After stenting, patients received aspirin and either ticlopidine or conventional anticoagulation (heparin or oral anticoagulant). The primary end point was the occurrence of bleeding or peripheral vascular complications; secondary end points were cardiac events (death, infarction, or stent occlusion) and duration of hospitalization. RESULTS: In 13 centers, 236 patients were randomized to anticoagulation and 249 to antiplatelet therapy. Stenting was elective in 58% of patients and unplanned in 42%. Stent implantation was successfully achieved in 99% of patients. A primary end point occurred in 33 patients (13.5%) in the antiplatelet group and 48 patients (21%) in the anticoagulation group (odds ratio=0.6 [95% CI 0.36 to 0.98], P=0.03). Major cardiac-related events in electively stented patients were less common (odds ratio=0.23 [95% CI 0.05 to 0.91], P=0.01) in the antiplatelet group (3 of 123, 2.4%) than the anticoagulation group (11 of 111, 9.9%). Hospital stay was significantly shorter in the antiplatelet group (4.3+/-3.6 versus 6. 4+/-3.7 days, P=0.0001). CONCLUSIONS: Antiplatelet therapy after coronary stenting significantly reduced rates of bleeding and subacute stent occlusion compared with conventional anticoagulation.

Administration, Oral↗

Randomized coronary patency trial of double-bolus recombinant staphylokinase versus front-loaded alteplase in acute myocardial infarction.

One hundred two patients with evolving myocardial infarction of 6 hours' duration were given aspirin and intravenous heparin and randomly allocated to intravenous front-loaded, weight-adjusted rTPA administration over a 90-minute period (52 patients) or to two 15 mg doses of recombinant staphylokinase, 30 minutes apart (50 patients). Thrombolysis in Myocardial infarction (TIMI) perfusion grade 3 at 90 minutes was achieved in 68% (95% confidence interval, 55% to 81%) of patients treated with staphylokinase versus 57% (95% confidence interval, 43% to 72%) of patients treated with rTPA (p = not significant). Double-bolus staphylokinase was significantly more fibrin-specific than accelerated rTPA with residual fibrinogen at 90 minutes of 105% +/- 4.1% and 68% +/- 7.5%, respectively (p < 0.0001). Thirteen patients in each study group underwent angioplasty of the culprit coronary artery within the first 24 hours because of suboptimal recanalization (TIMI < 3). In the patients without prior coronary intervention, TIMI 3 at 24 hours was 100% after staphylokinase administration (n = 35) versus 79% after rTPA (n = 34) (p = 0.005). The distribution of inhospital events did not significantly differ between both groups. One patient receiving rTPA died in the hospital from ischemic stroke. Staphylokinase administration did not induce allergic reactions, but significant staphylokinase-neutralizing activity (> 5 micrograms/ml) and specific anti-staphylokinase IgG developed in 73% of patients after 2 weeks. Thus two 15 mg doses of staphylokinase induce early, complete, and sustained coronary artery patency at least as frequently as accelerated rTPA without associated fibrinogen degradation but with subsequent induction of circulating neutralizing antibodies.

Female↗

Three-dimensional correction for spillover and recovery of myocardial PET images.

UNLABELLED: PET permits the quantification of myocardial blood flow, but is hampered by the limited spatial resolution of PET images. METHODS: We evaluated two methods for the correction of resolution effects in PET perfusion 13NH3-ammonia images. In one model, the spillover and recovery coefficients are estimated in the kinetic modeling analysis. The new, second model uses an explicit delineation of the left ventricular wall and a convolution model for the system point spread function to compute the regional values of the spillover and recovery coefficients. RESULTS: The new method is validated with phantom measurements. The two methods are evaluated on animal experiments using 13NH3-ammonia. Both two- and three- compartment models were used to compute absolute flow values. Excellent linear correlations with microsphere data were obtained. The slope of the regression line was lower for corrections based on kinetic modeling as compared to convolution-based correction. In animal experiments, recovery coefficients of 59% for the myocardial wall and 86% for the blood pool were obtained. Spillover from the blood pool into the myocardial was was 14%. CONCLUSION: The new correction method strongly suppresses spillover and recovery effects due to limited resolution.

Algorithms↗

A randomized trial of recombinant staphylokinase versus alteplase for coronary artery patency in acute myocardial infarction. The STAR Trial Group.

BACKGROUND: Recombinant staphylokinase (STAR) was shown recently to offer promise for coronary arterial thrombolysis in patients with evolving myocardial infarction. The present multicenter randomized open trial was designed to assess the thrombolytic efficacy, safety, and fibrin specificity of STAR relative to accelerated alteplase (recombinant tissue-type plasminogen activator [RTPA]). METHODS AND RESULTS: One hundred patients with evolving myocardial infarction of < 6 hours' duration and with ST-segment elevation were allocated to accelerated and weight-adjusted RTPA over 90 minutes (52 patients) or to STAR (the first 25 patients to 10 mg and the next 23 patients to 20 mg given intravenously over 30 minutes). All patients received aspirin and intravenous heparin. The main end points were coronary artery patency and plasma fibrinogen levels at 90 minutes. Thrombolysis in Myocardial Infarction (TIMI) perfusion grade 3 at 90 minutes was achieved in 62% of STAR patients versus 58% of RTPA patients (risk ratio, 1.1; 95% CI, 0.76 to 1.5). With 10 mg STAR, TIMI grade 3 patency was 50% (risk ratio, 0.86; 95% CI, 0.54 to 1.4 versus RTPA); with 20 mg STAR, it was 74% (risk ratio, 1.3; 95% CI, 0.90 to 1.8 versus RTPA). Residual fibrinogen levels at 90 minutes were 118 +/- 47% (mean +/- SD) of baseline with STAR and 68 +/- 42% with RTPA (P < .0005). STAR therapy was not associated with an excess mortality or electric, hemorrhagic, mechanical, or allergic complications. However, patients developed antibody-mediated STAR-neutralizing activity from the second week after STAR treatment. As an addendum to the randomized study, 5 patients were given 40 mg STAR over 30 minutes, resulting in TIMI perfusion grade 3 at 90 minutes in 4 patients without fibrinogen breakdown (residual levels at 90 minutes of 105 +/- 8% of baseline). CONCLUSIONS: STAR appears to be at least as effective for early coronary recanalization as and significantly more fibrin-specific than accelerated RTPA in patients with evolving myocardial infarction.

Angioplasty, Balloon, Coronary↗

Metabolism of nitrogen-13 labelled ammonia in different conditions in dogs, human volunteers and transplant patients.

To investigate the rate of metabolism of nitrogen-13 labelled ammonia (13NH3) in different conditions, we have determined the relative amount of unchanged 13NH3 in the blood of dogs, volunteers and transplant patients at different times following injection. In dogs, the determinations were made under basal conditions, during adenosine administration and after coronary occlusion. The results show that adenosine administration increases the metabolic rate whereas coronary occlusion does not affect 13NH3 metabolism. For both human volunteers and transplant patients the metabolic rate of 13NH3 was assessed under basal conditions and during adenosine administration. 13NH3 metabolism proceeds faster in transplant patients than in volunteers under both conditions. Adenosine administration causes a faster 13NH3 turnover in volunteers but not in transplant patients. Application of individual metabolite correction resulted in a 16% decrease in the calculated blood flow compared to uncorrected values. A smaller difference (5%) was observed between correction with mean metabolite values and individually acquired metabolite values.

Adenosine↗

In vivo comparison between two tip pressure transducer systems.

Experimental findings are presented of an in vivo comparison between a Sentron catheter and another tip transducer manometer: a Millar microtip catheter. Both catheters have been used simultaneously in the left ventricle of dogs. Pressure variations were elicited by drug infusion. Pressure values and derivatives obtained from both systems were compared. A cross correlation between episodes of the two pressures was computed. Results from this study showed good correlation between left ventricular systolic pressure measured with both manometers (R = 0.992, p < 0.0001), end-diastolic pressure (R = 0.809, p < 0.0001) and between first derivatives: positive derivative (R = 0.993, p < 0.0001) and negative (R = 0.634, p < 0.0001). The mean cross correlation between both pressure signals was 0.61 +/- 0.04. In the frequency domain no statistical difference was found between the location of the maxima of the peaks. It is concluded that a Sentron manometer can be a valid alternative, at a reasonable price, to a cheaper, though less accurate fluid filled catheter and a more expensive 'golden standard' microtip catheter.

Angiotensin-Converting Enzyme Inhibitors↗

Prevention of restenosis after coronary balloon angioplasty: rationale and design of the Fluvastatin Angioplasty Restenosis (FLARE) Trial. The FLARE Study Group.

Prevention of restenosis after successful percutaneous transluminal coronary balloon angioplasty (PTCA) continues to present the greatest therapeutic challenge in interventional cardiology. Experimental and pathological studies describe restenosis as no more than the biologic healing response to arterial injury. Studies of serial quantitative coronary angiography have demonstrated that this biologic process may be measured as the loss in minimal luminal diameter (MLD) from post-PTCA to follow-up angiography and that it is essentially ubiquitous and normally distributed. Thus, quantitative coronary angiography has become the gold standard for evaluation of the angiographic outcome of clinical trials of new agents and devices aimed at prevention of restenosis. The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors inhibit biosynthesis of mevalonate, a precursor of non-sterol compounds involved in cell proliferation, and thus may control the neointimal response, which forms the kernel of restenosis. Experimental evidence suggests that fluvastatin may exert a greater direct inhibitory effect on proliferating vascular myocytes than other HMG-CoA reductase inhibitors, independent of any lipid-lowering action. The Fluvastatin Angioplasty Restenosis (FLARE) Trial was conceived, in collaboration between the Thoraxcenter, Erasmus University, Rotterdam, The Netherlands, and Sandoz Pharma, to evaluate the ability of fluvastatin 40 mg twice daily to reduce restenosis after successful single-lesion PTCA. Treatment of suitable patients begins 2 weeks before PTCA and continues after successful PTCA (residual diameter stenosis < 50%, without major cardiac complications) to follow-up angiography at 26 +/- 2 weeks. Restenosis is measured by quantitative coronary angiography at a core laboratory as the loss in MLD from post-PTCA to follow-up angiography. It is calculated (90% power, alpha = 0.05) that 730 evaluable patients will be needed to test the hypothesis that fluvastatin will reduce the expected post-PTCA loss in MLD by 40%. Serial lipid analysis will be carried out at a central laboratory. Trial evaluation is focused on the primary endpoint (change in MLD) but includes primary clinical endpoints (death, myocardial infarction, or the need for coronary artery bypass graft surgery or reintervention up to 40 weeks after PTCA) as well as secondary and tertiary clinical, angiographic, and laboratory endpoints. According to this methodologic approach, the effect of fluvastatin in luminal renarrowing and clinical events after successful PTCA as well as possible associations of lipid parameters with restenosis can be comprehensively investigated.

Angioplasty, Balloon, Coronary↗

Usefulness of the Wiktor stent for treatment of threatened or acute closure complicating coronary angioplasty. The European Wiktor Stent Study Group.

The purpose of this study was to determine the results of the first Wiktor stent implantations in bailout conditions. From December 1990 to July 1991, in a total of 10 centers, 69 patients presenting with threatened or total closure after balloon angioplasty each received the Wiktor stent in 1 coronary artery. In these 69 coronary arteries, a total of 72 stent deliveries were attempted and 69 were successful (delivery success rate 95%). Delivery failure was treated conservatively in 2 patients and surgically in 1 patient. Emergency surgery was also performed in 2 patients, who after successful stent delivery showed progressive distal extension of the dissection. In addition, 5 patients underwent elective surgery to avoid the possibility of stent thrombosis because the myocardial area at risk was considered too large. Postprocedural blood transfusion was performed in 6% of the patients, whereas stent thrombosis occurred in 10 of 59 patients (17%), resulting in 2 deaths. Finally, 65% of the patients had a successful stent implantation without major periprocedural complications. At 6-month follow-up, only 9% of the patients experienced recurrent angina, whereas a > 50% arterial diameter narrowing was observed in 27% of the patients. Thus, the radiopaque Wiktor stent can be accurately and conveniently implanted in dissected coronary arterial segments. However, as for similar bailout devices, the number of thrombotic and bleeding events remains high.

Adult↗

The brachial approach for intracoronary stent implantation.

Aggressive anticoagulation after intracoronary stent implantation leads to an increased incidence of femoral hematomas and vascular complications. Out of 74 Medtronic Wiktor stent implantations, six were performed via right brachial artery cut-down. All six attempts were successful without stent closure, bleeding or vascular complications. We feel that intracoronary Wiktor stent implantation via the brachial approach is feasible. The open artery repair and uninterrupted anticoagulation may be an interesting advantage.

Brachial Artery↗

Angiotensin-converting enzyme inhibition with fosinopril sodium in the prevention of restenosis after coronary angioplasty.

BACKGROUND: Several angiotensin-converting enzyme inhibitors have antiproliferative effects in a rat model after carotid artery balloon injury. METHODS AND RESULTS: We conducted a randomized, double-blind, placebo-controlled trial to assess the effect of fosinopril, a novel angiotensin-converting enzyme inhibitor, in restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA). Patients received fosinopril or matched placebo 10 mg at least 18 hours before PTCA, 20 mg at least 4 hours before PTCA, and 40 mg daily for 6 months. In addition, all patients received aspirin. Coronary angiograms before PTCA and immediately after PTCA as well as at 6-month follow-up were quantitatively analyzed. A total of 509 patients were recruited. The final per-protocol population consisted of 153 fosinopril-treated and 151 placebo-treated patients. Restenosis rates according to the National Heart, Lung, and Blood Institute criterion 4 (loss of > or = 50% of the initial gain [primary end point]) were 45.7% and 40.7% in the fosinopril and control groups, respectively (not significant). The respective mean differences in minimal coronary luminal diameter between post-PTCA and follow-up angiograms were -0.59 +/- 0.71 mm and -0.51 +/- 0.67 mm (not significant). Clinical events during the 6-month follow-up period, analyzed on an on-treatment basis, were ranked according to the most serious event. The respective numbers in the fosinopril and the control groups were for death, 0 and 0; myocardial infarction, 0 and 0; coronary artery bypass graft surgery, 1 and 3; repeat PTCA, 35 and 35; recurrent signs of ischemia necessitating early repeat coronary angiography and managed medically, 6 and 7; and none of the above, 111 and 106. All these differences were significant. CONCLUSIONS: Administration of fosinopril in a dose of 40 mg daily during 6 months after PTCA does not prevent restenosis and has no effect on overall clinical outcome.

Angioplasty, Balloon, Coronary↗

Intra- and interobserver variability of a fast on-line quantitative coronary angiographic system.

To evaluate intra- and interobserver variability of an on-line quantitative coronary angiographic system, 2 independent observers measured 166 primary lesions excluding total occlusions before and after coronary angioplasty. Each observer repeated his measurement 3 times at 14 days interval. The average percent diameter stenosis results obtained by observer 1 and 2 were almost identical, before (62.2% +/- 12.0% and 62.6% +/- 11.4%, NS) and after (27.1% +/- 12.0% and 26.9% +/- 11.3%, NS) angioplasty. Variability was expressed as 95% limits of agreement (mean difference +/- 2 x SD). The intra-observer variability of observer 1 ranged from -6.6% to 6.6% before angioplasty and from -9.6% to 9.6% after angioplasty. The corresponding limits of observer 2 were -8.0% to 7.5% and -8.3% to 8.5%, respectively. The interobserver variability ranged from -10.4% to 9.6% before versus -12.5% to 13.1% after angioplasty. This variability was not influenced by vessel size. The widening of the limits observed after angioplasty was largely due to an increased variability in the measurements of the absolute minimal luminal diameter but not of the reference segment. We conclude that the intra- and interobserver variability of measurements obtained with an on-line quantitative angiographic system used for guiding coronary interventions is acceptable and without systematic bias in any direction for a wide range of primary coronary stenoses. However, the variability increases when images are acquired immediately after angioplasty.

Angioplasty, Balloon, Coronary↗

Echocardiographic detection of acute myocardial ischemia during percutaneous transluminal coronary angioplasty.

The usefulness of echocardiography and Doppler for the detection of acute myocardial ischemia was evaluated during right coronary artery occlusion in 20 patients. The echocardiographic findings were compared with the occurrence of chest pain, and to electrocardiographic and hemodynamic changes obtained during percutaneous transluminal coronary angioplasty. Our results confirm that, even in the case of small segmental myocardial ischemia, two-dimensional echocardiography is superior to all other measured parameters. In contrast, Doppler examination of transmitral flow is not sensitive enough for the detection of such small segmental myocardial ischemia induced by right coronary artery occlusion.

Adult↗

Immediate and follow-up results of the conservative coronary angioplasty strategy for unstable angina pectoris.

To assess the results of a conservative coronary angioplasty strategy in unstable angina pectoris, the records of 1,421 consecutive patients without previous myocardial infarction undergoing a first percutaneous transluminal coronary angioplasty (PTCA) between 1986 and 1990 were reviewed. Of these patients, 631 had unstable and 790 had stable angina pectoris. Only after an intense effort to medically control symptoms, the unstable patients underwent PTCA at an average of 15.4 days (range 1 to 76) after hospital admission. Primary clinical success was achieved in 91.7% of patients with unstable and in 94.4% of those with stable angina pectoris (p = not significant). In-hospital mortality rates were 0.3 and 0.1%, respectively (p = not significant). Nonfatal in-hospital event rates for acute myocardial infarction, cerebrovascular accident and coronary bypass surgery were only slightly higher in patients with unstable angina pectoris; however, the difference from the stable group was significant when all events were combined (9 vs 5.9%; p less than 0.04). During 6-month follow-up, no significant difference in adverse events was found between the groups. The respective rates for the unstable and stable groups were 0.4 and 0.2% for death, 5.5 and 5.1% for major nonfatal events, and 17.7 and 20.1% for repeat PTCA. These results suggest that use of a conservative PTCA strategy in the treatment of patients with unstable angina pectoris results in favorable and similar immediate and 6-month outcomes compared with those in patients with stable angina pectoris.

Angina Pectoris↗

Isolated single coronary artery: a review of 50,000 consecutive coronary angiographies.

Single coronary artery is a rare congenital anomaly of the coronary arteries where only one coronary artery arises from the aortic trunk by a single coronary ostium, supplying the entire heart. A database consisting of the angiographic reports of 50,000 consecutive coronary angiographies performed in adult patients in the University Hospital of Leuven between March 1973 and August 1991 was searched for the diagnosis of single coronary artery. All films concerned were reviewed and classified according to their anatomical type. Thirty-three cases of single coronary artery were retrieved, yielding an incidence of 0.066%. Patient characteristics and clinical data are described, with a discussion on the pathological importance of this finding.

Adult↗

Reperfusion intervention in acute myocardial infarction.

Over the past year, the results of large-scale trials have better defined the risk to benefit ratios of thrombolytic therapy in specific subgroups of patients. However, important issues such as prevention of early reocclusion, prehospital administration of thrombolytics, adjunctive treatment with beta-blockers or angiotensin-converting enzyme inhibitors and early noninvasive detection of reperfusion remained unsolved. Encouraging data have been reported in selected patients for the more aggressive approach of direct angioplasty without thrombolysis. However, the results from large, randomized trials, comparing direct angioplasty with conventional thrombolysis, are still lacking. A postthrombolysis strategy of watchful waiting has been corroborated by new findings.

Angioplasty, Balloon, Coronary↗