Accuracy of echocardiographic assessment of pulmonary hypertension severity and right ventricular dysfunction in patients with chronic thromboembolic pulmonary hypertension.

AIM: Chronic thromboembolic pulmonary hypertension (CTEPH) results from chronic thrombotic occlusion of the pulmonary arterial circulation and may be potentially cured by pulmonary thromboendarterectomy. Echocardiography is the most practical modality for the assessment of right ventricular function and right heart pressures before and after surgery. However, there is scant data on how these estimates compare with the "gold standards" of invasive right heart catheterization and CT and MR scanning. METHODS: The records of 100 consecutive patients with CTEPH who subsequently underwent pulmonary thromboendarterectomy at our institution were studied. Right atrial (RA) and right ventricular (RV) systolic pressure estimated at preoperative echocardiography were compared with measurements at preoperative cardiac catheterization. In addition, preoperative echocardiographic estimates of RV systolic function by visual assessment and by calculation of RV index of myocardial performance were compared with preoperative measurements of RV ejection fraction (EF) by computed tomography (CT) or magnetic resonance (MR) scanning. RESULTS: Although estimates of RA and PA systolic pressures by echocardiography correlated significantly with those at cardiac catheterization (p<0.0001) in patients with CTEPH, Bland-Altman analysis demonstrated significant variation in these measurements compared with cardiac catheterization. Cohen's Kappa analysis demonstrated that agreement between echo and cath derived values was slight (κ=0.1). RVEF assessed by CT or MR scanning correlated with echocardiographic visual assessment of RV systolic function (P<0.0001), and with RIMP (P=0.001), but actual measurements of right ventricular ejection fraction at a given assessment of right ventricular function by RIMP or visual assessment varied widely CONCLUSION: Caution is warranted in over-reliance on echo derived measurements of right heart hemodynamics and function in the setting of pulmonary hypertension, and where the clinical scenario calls the data into question, a low threshold should be maintained for proceeding to more advanced and invasive modalities of evaluation.

TNK-tPA for acute myocardial infarction: the clinical experience.

Thrombolytic therapy has become the mainstay of treatment for acute transmural myocardial infarction. Present fibrinolytic regimens have a number of shortcomings, including the failure to induce early and sustained reperfusion in as many as 40-50% of the patients, and to prevent reocclusion in another 10-20% of the patients. The efforts for improving thrombolysis are focused on the development of new agents (fibrinolytics, anticoagulants, and antiplatelet agents). TNK-tPA is a triple combination mutant of wild-type tissue plasminogen activator that exhibits a longer plasma half-life, an enhanced fibrin-specificity, and an increased resistance to the plasminogen activator inhibitor-1. This paper summarizes the results of clinical trials with TNK-tPA in acute myocardial infarction.

Comparison of a synthetic antithrombin III-binding pentasaccharide and standard heparin as an adjunct to coronary thrombolysis.

The effects on alteplase-induced thrombolysis of the synthetic ATIII-binding pentasaccharide SR90107A/ORG 31540 (synthetic pentasaccharide, SP) and of standard heparin (SH) were compared in a copper coil model of coronary artery thrombosis in 6 groups of 10 dogs. After 1 h of occlusion, all animals received intravenously alteplase and aspirin, and were randomly assigned to a 2 h infusion of either saline, or one of two doses of SH (100 IU/kg bolus plus 50 IU/kg/h infusion, or 200 IU/kg bolus plus 100 IU/kg/h infusion), or one of three doses of SP (100 nmol/kg bolus plus 50 nmol/kg/h infusion, 200 nmol/kg bolus plus 100 nmol/kg/h infusion, or 400 nmol/kg bolus plus 200 nmol/kg/h infusion). Coronary angiography was performed every 10 min for 4 h. Appropriate doses of SP and SH enhanced alteplase-induced thrombolysis to a similar extent. In contrast, SP was devoid of any anti-IIa activity or aPTT prolongation.

Is there a change in myocardial nonlinearity during the cardiac cycle?

The distortion of a sound wave during propagation results in progressive transfer of the energy from fundamental to higher harmonics, and is dependent on the nonlinearity of the medium. We studied if relative changes in acoustical nonlinearity occur in healthy myocardium during the cardiac cycle. Radiofrequency data were acquired from transthoracic echocardiography (2.5 and 3.5 MHz), parasternal long axis view, from five dogs and nine healthy volunteers. Integrated backscatter was calculated after filtering for fundamental (FIB) and second harmonic frequencies (SHIB), from a region in the posterior myocardial wall. The results suggest that there is little difference between the SHIB and FIB, although there were large variations between individuals. The maximal changes in nonlinearity, as estimated by SHIB/FIB ratio, mostly occurred during systole. SHIB presented similar cyclic variation with FIB (p = NS). Further studies are necessary to separate the role of myocardial nonlinearity, attenuation, propagating distance, or acoustical properties of the blood. The results are important in further tissue characterization studies employing second harmonic data.

Infarct size, myocardial hemorrhage, and recovery of function after mechanical versus pharmacological reperfusion: effects of lytic state and occlusion time.

BACKGROUND: Whether myocardial reperfusion obtained with thrombolysis or primary angioplasty is associated with a similar recovery of function and with the same risk of hemorrhagic infarction is unknown. We evaluated the effects of mechanical and pharmacological reperfusion (with or without a plasma lytic state) on infarct size, myocardial hemorrhage, and left ventricular (LV) function in a canine model. METHODS AND RESULTS: Six groups of six dogs were subjected to balloon occlusion of the left anterior descending coronary artery (LAD) followed by 2 hours of reperfusion. The study had a two-by-three factorial design with two occlusion periods (90 and 240 minutes) and three different reperfusion strategies (placebo, 0.4 mg/kg recombinant tissue plasminogen activator, and 40 microg/kg recombinant staphylokinase). In a seventh control group, LAD occlusion was maintained without reperfusion. All dogs received aspirin and heparin. A systemic lytic state was present in staphylokinase-treated dogs. Planimetry of LV slices showed larger infarcts (percent of area at risk) and more hemorrhage (percent of IA) after 240 minutes of occlusion than after 90 minutes of occlusion (54+/-17% versus 37+/-18% and 52+/-27% versus 29+/-27%, respectively; P<.01 for both comparisons), with no significant difference among treatments. Hemorrhage was not observed in the control group without reperfusion. LV angiography showed no differences in global and regional LV function between mechanical and pharmacological reperfusion. CONCLUSIONS: In this experimental model, hemorrhagic infarctions of similar extent were observed after both pharmacological and mechanical reperfusion. The extent of hemorrhage was increased by the delay in reperfusion but not by the presence of a lytic state.

Noninvasive measurements of infarct size after thrombolysis with a necrosis-avid MRI contrast agent.

BACKGROUND: Gadophrin-2 is a new MRI contrast agent with high affinity for necrotic myocardium. The aim of the study was to evaluate whether noninvasive measurements of infarct size after thrombolysis are possible with gadophrin-2-enhanced MRI. METHODS AND RESULTS: Coronary artery thrombosis was induced in 3 groups of dogs by the copper-coil technique. Thrombolytic therapy together with aspirin and heparin was initiated after 90 minutes of occlusion. One day (group A), 2 days (group B), or 6 days (group C) after infarction, gadophrin-2 was injected intravenously (50 micromol. kg-1). In vivo T1-weighted segmented turbo-FLASH, in vivo T2-weighted segmented half-Fourier turbo spin echo (HASTE), and T1- and T2-weighted spin-echo MRI of the excised heart were performed 24 hours after gadophrin-2 injection. Regions of strong enhancement were observed on T1-weighted images. Planimetry of short-axis MR images and of corresponding triphenyltetrazolium chloride (TTC)-stained left ventricular (LV) slices showed a close correlation between the enhanced areas and TTC-negative areas for both in vivo (r2=0.98, P<0.0001; mean difference, 0.9+/-2.0% [SD] of the LV volume [LVV]) and postmortem (r2=0.99, P<0.0001; mean difference, 0.9+/-1.4% of LVV) measurements. T2-weighted images overestimated the infarct size by 8.1+/-5.4% of LVV. The mean infarct size was 10.8+/-11.6% of LVV (group A), 22.4+/-11.7% (group B), and 5.1+/-9.3% (group C). CONCLUSIONS: In this animal model, in vivo gadophrin-2-enhanced MRI could precisely determine infarct size after thrombolytic therapy. This technique may be very useful for the noninvasive evaluation of infarct size after reperfusion for AMI.