Sirolimus and tacrolimus in clinical cardiac transplantation.
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Adult↗
Biomedical subjects
R F Sequeira
Publications and source records attributed to R F Sequeira.
Thrombosed chamber of cor-triatriatum mimicking left atrial tumor (case report).
Cor-triatriatum is an uncommon congenital cardiac anomaly. In this case report, transesophageal echocardiographic and operative findings in a 57-year-old female with cor-triatriatum are presented.
Cor Triatriatum↗
First report of an intravenous and oral glycoprotein IIb/IIIa inhibitor (RPR 109891) in patients with recent acute coronary syndromes: results of the TIMI 15A and 15B trials.
BACKGROUND: RPR 109891 is a modified tetrapeptide glycoprotein IIb/IIIa inhibitor available in intravenous and oral formulations. Two phase II dose-ranging studies were performed to investigate pharmacodynamics and safety in acute coronary syndromes. METHODS: The Thrombolysis In Myocardial Infarction (TIMI) 15A trial was a randomized, open-label, study of RPR 109891 administered intravenously for 24 to 96 hours in 91 patients. TIMI 15B was a randomized, double-blind comparison of intravenous RPR 109891 plus 4 weeks of oral RPR 109891 (n = 142) compared with placebo (n = 50). RESULTS: Intravenous RPR 109891 exhibited a dose-response inhibition of platelet aggregation; mean inhibition after a bolus ranged from 53% to 92%, and at steady state 49% to 98%. Oral RPR 109891 demonstrated less platelet inhibition (peaks, range 48% to 59%; troughs, range 18% to 39%). Mean glycoprotein IIb/IIIa receptor occupancy and platelet inhibition were highly correlated (r = 0.82, 95% confidence interval 0.74-0.88). There were trends for increased major hemorrhage (10% vs 6%, P =.57), thrombocytopenia <90,000 cells/mm(3) (13% vs 4%, P =.11), and profound thrombocytopenia <20, 000 (3.5% vs 0%, P =.33) with intravenous plus oral RPR 109891 compared with placebo. In 3 of 5 cases of profound thrombocytopenia, RPR 109891 had been interrupted because of bypass surgery, and a precipitous fall in platelet count occurred after the first postoperative oral dose. CONCLUSIONS: Intravenous RPR 109891 is a potent, predictable, dose-related platelet inhibitor. Oral RPR 109891 (</=600 mg/d) achieves moderate platelet inhibition. Interrupted glycoprotein IIb/IIIa blockade may be associated with a higher risk of profound thrombocytopenia and deserves closer examination in future studies.
Administration, Oral↗
Weight-adjusted dosing of TNK-tissue plasminogen activator and its relation to angiographic outcomes in the thrombolysis in myocardial infarction 10B trial. TIMI 10B Investigators.
Fixed doses of thrombolytic agents are generally administered to patients of varying body weights, and the dose-response relation may be confounded by the variability in patient weight. We hypothesized that higher doses of TNK-tissue plasminogen activator (tPA) per unit body weight would be related to improved flow at 90 minutes after thrombolytic administration. A total of 886 patients with acute myocardial infarction were randomized to receive either a single bolus of 30, 40, or 50 mg of TNK-tPA or front-loaded tPA in the Thrombolysis In Myocardial Infarction (TIMI) 10B trial. The dose of TNK-tPA administered was divided by the patient's weight to arrive at the TNK-tPA dose (mg) per unit body weight (kg), and patients were stratified into tertiles based on mg/kg of TNK-tPA: low dose, 0.2 to 0.39 mg/kg; mid-dose, 0.40 to 0.51 mg/kg; high dose, 0.52 to 1.24 mg/kg. Flow in the culprit and nonculprit arteries was analyzed using the TIMI flow grades and the corrected TIMI frame count (CTFC). The median CTFC in culprit arteries differed between the tertiles (3-way p = 0.007), with the CTFC being 7.2 frames faster in high-dose than in low-dose patients (43.1 +/- 30.1, median 31.2, n = 171 vs 54.6 +/- 34.8, median 38.4, n = 166, 2-way p = 0.002). Patients in the mid- and high-dose tertiles achieved patency more frequently (TIMI grade 2 or 3 flow) by 60 minutes (p = 0.02), and the 90-minute percent diameter stenosis was less severe in patients in the high- versus low-dose tertile (p = 0.03). In nonculprit arteries, the CTFC was faster in high- than in low-dose tertiles (29.6 +/- 13.4, median 26.9, n = 130 vs 34.7 +/- 16.3, median 32.8, n = 108, 3-way p = 0.03, 2-way p = 0.008). In patients who underwent percutaneous transluminal coronary angioplasty (PTCA), the CTFC in culprit arteries after PTCA was fastest in the high- and mid-dose tertiles than in those receiving low doses (2-way p = 0.05). Thus, higher doses per unit body weight of TNK-tPA result in not only faster culprit artery flow, but also faster nonculprit, global, and post-PTCA flow, which may reflect earlier opening, reduced stunning, or improved microvascular function. The greater effectiveness of thrombolysis must be weighed against any increase in risk.
Adult↗
Determinants of coronary blood flow after thrombolytic administration. TIMI Study Group. Thrombolysis in Myocardial Infarction.
OBJECTIVES: This study evaluated the determinants of coronary blood flow following thrombolytic administration in a large cohort of patients. BACKGROUND: Tighter residual stenoses following thrombolysis have been associated with slower coronary blood flow, but the independent contribution of other variables to delayed flow has not been fully explored. METHODS: The univariate and multivariate correlates of coronary blood flow at 90 min after thrombolytic administration were examined in a total of 2,195 patients from the Thrombolysis in Myocardial Infarction (TIMI) 4, 10A, 10B and 14 trials. The cineframes needed for dye to first reach distal landmarks (corrected TIMI frame count, CTFC) were counted as an index of coronary blood flow. RESULTS: The following were validated as univariate predictors of delayed 90-min flow in two cohorts of patients: a greater percent diameter stenosis (p < 0.0001 for both cohorts), a decreased minimum lumen diameter (p = 0.0003, p = 0.0008), a greater percent of the culprit artery distal to the stenosis (p = 0.03, p = 0.02) and the presence of any of the following: delayed achievement of patency (i.e., between 60 and 90 min) (p < 0.0001 for both cohorts), a culprit location in the left coronary circulation (left anterior descending or circumflex) (p = 0.02, p < 0.0001), pulsatile flow (i.e., reversal of flow in systole, a marker of heightened microvascular resistance, p = 0.0003, p < 0.0001) and thrombus (p = 0.002, p = 0.03). Despite a minimal 16.4% residual stenosis following stent placement, the mean post-stent CTFC (25.8 +/- 17.2, n = 181) remained significantly slower than normal (21.0 +/- 3.1, n = 78, p = 0.02), and likewise 34% of patients did not achieve a CTFC within normal limits (i.e., <28 frames, the upper limit of the 95th percent confidence interval previously reported for normal flow). Those patients who failed to achieve normal CTFCs following stent placement had a higher mortality than did those patients who achieved normal flow (6/62 or 9.7% vs. 1/118 or 0.8%, p = 0.003). CONCLUSIONS: Lumen geometry is not the sole determinant of coronary blood flow at 90 min following thrombolytic administration. Other variables such as the location of the culprit artery, the duration of patency, a pulsatile flow pattern and thrombus are also related to slower flow. Despite a minimal 16% residual stenosis, one-third of the patients treated with adjunctive stenting still have a persistent flow delay following thrombolysis, which carries a poor prognosis.
Angioplasty, Balloon, Coronary↗
Transdermal nitroglycerin patch therapy improves left ventricular function and prevents remodeling after acute myocardial infarction: results of a multicenter prospective randomized, double-blind, placebo-controlled trial.
BACKGROUND: Nitrates are widely used in the treatment of angina in patients with acute myocardial infarction (AMI). Short-term administration prevents left ventricular (LV) dilation and infarct expansion. However, little information is available regarding their long-term effects on LV remodeling in patients surviving Q-wave AMI. METHODS AND RESULTS: This was a randomized, double-blind, placebo-controlled trial designed to investigate the long-term (6-month) efficacy of intermittent transdermal nitroglycerin (NTG) patches on LV remodeling in 291 survivors of AMI. Patients meeting entry criteria had baseline gated radionuclide angiography (RNA) followed by randomization to placebo or active NTG patches delivering 0.4-, 0.8-, or 1.6-mg/h. RNA was repeated at 6 months and 6.5 days after withdrawal of double-blind medication. The primary study end point was the change in end-systolic volume index (ESVI). Both ESVI and end-diastolic volume index (EDVI) were significantly reduced with 0.4-mg/h NTG patches (-11.4 and -11.6 mL/m2, respectively, P<.03). This beneficial effect was observed primarily in patients with a baseline LV ejection fraction < or =40% (deltaESVI, -31 mL/m2; deltaEDVI, -33 mL/m2; both P<.05) and only at the 0.4-mg/h dose. After NTG patch withdrawal, ESVI significantly increased but did not reach pretreatment values. CONCLUSIONS: Transdermal NTG patches prevent LV dilation in patients surviving AMI. The beneficial effects are limited to patients with depressed LV function and only at the lowest (0.4-mg/h) dose. Continued administration is necessary to maintain efficacy. Whether these remodeling effects confer a clinical or survival advantage will need to be addressed in an adequately powered cardiac event trial.
Administration, Cutaneous↗
Prospective validation of a composite end point in thrombolytic trials of acute myocardial infarction (TIMI 4 and 5). Thrombosis In Myocardial Infarction.
Although the use of composite end points in clinical trials has increased in recent years, few data are available on the validity of such an approach. In the Thrombolysis In Myocardial Infarction (TIMI) 4 and 5 trials, we set out to validate prospectively the nonfatal components of the "unsatisfactory outcome" end point. This end point consisted of the in-hospital occurrence or observation of new-onset severe congestive heart failure/shock, left ventricular ejection fraction <40% (or <30% for patients with prior myocardial infarction), reinfarction, reocclusion by sestamibi perfusion imaging, TIMI flow grade <2 at 90 minutes or 18 to 36 hours, intracranial hemorrhage, major spontaneous hemorrhage, or anaphylaxis. Among 576 patients in TIMI 4 and 5 with 1-year follow-up, a nonfatal unsatisfactory outcome end point was reached in hospital in 45% of patients. Compared with patients without such an end point, patients with an end point had a relative risk of 1-year mortality of 2.5 (95% confidence interval 1.4 to 5.6, p = 0.001). For individual components, new-onset severe congestive heart failure/shock had a relative risk of 4.6 (p = 0.001), left ventricular ejection fraction <40% had a relative risk of 3.5 (p = 0.006), recurrent myocardial infarction had a relative risk of 2.2 (p = 0.047), and TIMI flow grade <2 at 90 minutes had a relative risk of 2.2 (p = 0.005). Our findings show that these nonfatal in-hospital end points and the composite end point are associated with an increased risk of 1-year mortality and as such are valid predictive survival markers for use in clinical trials.
Aged↗
Rescue angioplasty in the thrombolysis in myocardial infarction (TIMI) 4 trial.
Rescue percutaneous transluminal coronary angioplasty (PTCA) has been used to establish reperfusion after failed thrombolysis, and the goal of this study was to examine the angiographic and clinical outcomes after rescue PTCA performed for an occluded artery 90 minutes after thrombolysis. Four hundred two patients with acute myocardial infarction were randomized to receive either anistreplase (APSAC), recombinant tissue plasminogen activator, or their combination in the Thrombolysis in Myocardial Infarction (TIMI) 4 trial. The angiographic and clinical outcomes of patients with a patent artery 90 minutes after thrombolysis were compared with those of patients with an occluded artery treated in a nonrandomized fashion with either rescue or no rescue PTCA. At 90 minutes, the number of frames required to opacify standard landmarks (corrected TIMI frame count) was significantly lower (i.e., flow was faster) after successful rescue PTCA (27 +/- 11) than that in patent arteries after successful thrombolysis (39 +/- 20, p < 0.001), and the incidence of TIMI grade 3 flow was correspondingly higher after successful rescue PTCA (87% vs 65%, p = 0.002). In-hospital adverse outcomes (death, recurrent acute myocardial infarction, severe congestive heart failure, cardiogenic shock or an ejection fraction <40%) occurred in 29% of successful rescue PTCAs and in 83% of failed rescue PTCAs (p = 0.01). Among all patients in whom rescue PTCA was performed (successes and failures combined), 35% of patients experienced an adverse outcome, which was the same as the 35% incidence observed in patients not undergoing rescue PTCA (p = NS) and tended to be higher than the 23% incidence observed in patients with patent arteries (p = 0.07). Although successful rescue PTCA for an occluded artery at 90 minutes results in restoration of flow that is superior to that of successful thrombolysis, the incidence of adverse events for the strategy of rescue PTCA as a whole was the same as that of undertaking no PTCA.
Age Factors↗
TNK-tissue plasminogen activator in acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) 10A dose-ranging trial.
BACKGROUND: TNK-tissue plasminogen activator (TNK-TPA) is a genetically engineered variant of TPA, which in experimental models has a slower plasma clearance and greater fibrin specificity and is 80-fold more resistant to plasminogen activator inhibitor-1 than alteplase TPA. METHODS AND RESULTS: The thrombolysis in Myocardial Infarction (TIMI) 10A trial was a Phase 1, dose-ranging pilot trial designed to evaluate the pharmacokinetics, safety, and efficacy of TNK-TPA in patients with acute myocardial infarction. One hundred thirteen patients with acute ST-segment elevation myocardial infarction presenting within 12 hours and without contraindications to thrombolysis were enrolled and treated with a single bolus of TNK-TPA over 5 to 10 seconds with doses ranging from 5 to 50 mg. TNK-TPA demonstrated a plasma clearance of 151 +/- 55 mL/min and a half-life of 17 +/- 7 minutes. Comparable values for wild-type TPA are 572 +/- 132 mL/min and 3.5 +/- 1.4 minutes, respectively. Systemic fibrinogen and plasminogen levels fell by only 3% and 13%, respectively, at 1 hour after TNK-TPA administration. TIMI grade 3 flow at 90 minutes was achieved in 57% to 64% of patients at the 30- to 50-mg doses. Seven patients (6.2%) experienced a major hemorrhage, which occurred at a vascular access site in six patients. CONCLUSIONS: TNK-TPA has a prolonged half-life so it can be administered as a single bolus. TNK-TPA appears to be very fibrin specific, and the initial patency and safety profiles are encouraging. Further study of this new thrombolytic agent is ongoing.
Adult↗
ST segment tracking for rapid determination of patency of the infarct-related artery in acute myocardial infarction.
OBJECTIVES: This study was designed to test the hypothesis that monitoring the ST segment on a single electrocardiographic (ECG) lead reflecting activity in the infarct zone provides sensitive and specific recognition of reperfusion within 60 min of initiation of therapy in acute myocardial infarction. BACKGROUND: Infarct-related arteries that fail to recanalize early may benefit from immediate rescue angioplasty. Hence, detection of reperfusion has important practical clinical implications. METHODS: Of 41 patients with acute myocardial infarction who had ambulatory ECG (Holter) monitors placed, 38 had adequate ST segment monitoring for 3 h; 35 of the 38 were treated with thrombolytic agents and 3 with primary angioplasty. All patients underwent early coronary angiography and were classified into two groups: Group P (22 patients) had angiographic patency (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3 flow), the Group O (16 patients) had persistent occlusion (TIMI grade 0 or 1 flow) of the infarct-related vessel at 60 min from initiation of therapy. The initial ST segment level was defined as the first ST segment level recorded; the peak ST segment level was defined as the highest ST segment level measured during the 1st 60 min. To assess the optimal ST segment recovery criteria for reperfusion, the presence or absence of a > or = 75%, > or = 50% and > or = 25% decrement from initial and peak ST segment levels, sampled and analyzed at 2.5-, 5-, 10-, 15-and 20-min intervals, was correlated with patency of the infarct-related artery at 60 min. RESULTS: ST segment recovery of > or = 50% reduction from peak ST segment levels with sampling rates at < or = 10-min intervals provided the optimal criterion for recognizing coronary artery patency at 60 min (sensitivity 96%, 95% confidence interval [CI] 77% to 99%; specificity 94%, 95% CI 69% to 99%, p < 0.0001). The subgroup of 13 patients in Group P with TIMI grade 3 reperfusion flow all met this criterion (sensitivity 100%, 95% CI 75% to 100%). The use of the initial ST segment level as the baseline for determining the presence of a > or = 50% reduction in ST segment levels within 60 min was less sensitive. Prediction of coronary reperfusion within 60 min of therapy on the basis of a > or = 75% decrement from peak ST segment levels was less sensitive, and the use of a > or = 25% decrement was less specific. CONCLUSIONS: ST segment monitoring of a single lead reflecting the infarct zone provides a reliable method for assessing reperfusion within 60 min of acute myocardial infarction. Optimal criteria for ECG reperfusion include a > or = 50% decrease from peak ST segment levels, with ST segment measurements recorded continuously or at least every 10 min.
Anistreplase↗
Comparison of digitized ECGs simultaneously recorded with CR and V leads.
Evidence is presented that electrocardiograms recorded with bipolar chest-right arm (CR) leads are diagnostically similar to electrocardiograms recorded with unipolar V leads. Electrocardiograms were simultaneously recorded with CR and V leads on six chest sites in 45 cardiac patients and submitted, unmarked, for evaluation, by four cardiologists. In spite of relatively small differences in the amplitudes of P, Q, R, S, and T waveforms, the diagnosis based on tracings recorded with CR leads was similar to the diagnosis based on tracings recorded with V leads in nearly 90% of patients. Because CR leads are set up with only two electrodes, one on the right arm and one on the chest, their use in cardiac emergencies saves time and simplifies the recording technique. This investigation is part of a project aimed at developing a portable electrocardiograph for use outside the hospital or clinic.
Electrocardiography↗
Comparison of front-loaded recombinant tissue-type plasminogen activator, anistreplase and combination thrombolytic therapy for acute myocardial infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) 4 trial.
OBJECTIVES: The aim of our study was to determine a superior thrombolytic regimen from three: anistreplase (APSAC), front-loaded recombinant tissue-type plasminogen activator (rt-PA) or combination thrombolytic therapy. BACKGROUND: Although thrombolytic therapy has been shown to reduce mortality and morbidity after acute myocardial infarction, it has not been clear whether more aggressive thrombolytic-antithrombotic regimens could improve the outcome achieved with standard regimens. METHODS: To address this issue, 382 patients with acute myocardial infarction were randomized to receive in a double-blind fashion (along with intravenous heparin and aspirin) APSAC, front-loaded rt-PA or a combination of both agents. The primary end point "unsatisfactory outcome" was a composite clinical end point assessed through hospital discharge. RESULTS: Patency of the infarct-related artery (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3 flow) at 60 min after the start of thrombolysis was significantly higher in rt-PA-treated patients (77.8% vs. 59.5% for APSAC-treated patients and 59.3% for combination-treated patients [rt-PA vs. APSAC, p = 0.02; rt-PA vs. combination, p = 0.03]). At 90 min, the incidence of both infarct-related artery patency and TIMI grade 3 flow was significantly higher in rt-PA-treated patients (60.2% had TIMI grade 3 flow vs. 42.9% and 44.8% of APSAC- and combination-treated patients, respectively [rt-PA vs. APSAC, p < 0.01; rt-PA vs. combination, p = 0.02]). The incidence of unsatisfactory outcome was 41.3% for rt-PA compared with 49% for APSAC and 53.6% for the combination (rt-PA vs. APSAC, p = 0.19; rt-PA vs. combination, p = 0.06). The mortality rate at 6 weeks was lowest in the rt-PA-treated patients (2.2% vs. 8.8% for APSAC and 7.2% for combination thrombolytic therapy [rt-PA vs. APSAC, p = 0.02; rt-PA vs. combination, p = 0.06]). CONCLUSIONS: Front-loaded rt-PA achieved significantly higher rates of early reperfusion and was associated with trends toward better overall clinical benefit and survival than those achieved with a standard thrombolytic agent or combination thrombolytic therapy. These findings support the concept that more rapid reperfusion of the infarct-related artery is associated with improved clinical outcome.
Aged↗
Acute right ventricular infarction mimicking extensive anterolateral wall injury.
A patient presented with an acute right ventricular infarction characterized by an electrocardiographic current of injury in both the inferior (2,3,aVF) and anterior precordial leads (V1-V6). Cardiac catheterization demonstrated normal left ventricular wall motion, a codominant circulation, and severe disease of the right coronary artery. We propose that this coronary anatomy explains the injury currents on the electrocardiogram. This case illustrates a rare presentation of right ventricular myocardial infarction mimicking an extensive anterolateral wall injury.
Coronary Angiography↗
Acute ventricular septal rupture. Angiographic-morphologic features and clinical assessment.
Twenty patients with acute ventricular septal rupture underwent cardiac catheterization. Prior to catheterization, 17 patients were in Killip class 3-4. Mean cardiac index and cardiac output were 2.03 +/- 0.81 L/min/m2 and 3.55 +/- 1.33 L/min, respectively. Based on a recent pathologic description of septal rupture, we encountered by angiography and during surgery, two morphologic types of rupture: simple type which appears as a direct through-and-through communication between the ventricles, and complex type which presents hemorrhagic tracts in the septum with the opening into the ventricles at different levels. Considering the management of patients with septal rupture and the clinical outcome in our series, it is suggested that there is a need to minimize invasive angiographic procedures prior to early surgical correction of the ruptured septum.
Acute Disease↗
Detection of thrombosed aortic Björk-Shiley valve by two-dimensional echocardiography.
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Aortic Valve↗
Detection of posterior mediastinal lymphoma by pulsed Doppler echocardiography.
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Echocardiography↗
Prophylactic use of lidocaine to prevent advanced ventricular arrhythmias during pulmonary artery catheterization. Prospective double-blind study.
To determine whether prophylactic lidocaine could decrease the incidence of advanced ventricular arrhythmias, 62 patients undergoing 67 pulmonary artery catheterizations were given lidocaine or placebo before and during catheterization. Advanced ventricular arrhythmias occurred in 42 of the 67 catheterizations (63 percent). In 18 of 31 patients receiving lidocaine (58 percent) arrhythmias developed, whereas 24 of 36 patients who received placebo (67 percent) had evidence of arrhythmias. These differences were not significant. However, patients with catheterization times of less than 20 minutes who were treated with lidocaine had less ectopy (25 percent) than patients treated with placebo (68 percent) (p less than 0.05). Two patients has sustained ventricular tachycardia and both were receiving placebo. No complications of lidocaine prophylaxis were noted. Prophylactic lidocaine appears to decrease the incidence of mechanically induced arrhythmias in critically ill patients undergoing catheterization that is not prolonged.
Adult↗
Transcutaneous aortovelography as a measure of central blood flow [proceedings].
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Blood Flow Velocity↗