Late (five to eight years) clinical and angiographic assessment of patients undergoing successful percutaneous transluminal coronary angioplasty.
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Biomedical subjects
Publications and source records attributed to D O Williams.
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A young woman with Still's disease sustained a small myocardial infarction 12 weeks after the delivery of a healthy male infant. This pregnancy was complicated by late onset proteinuric hypertension. Coronary angiography nine days after infarction revealed intracoronary thrombus which had resolved by 3 months with antithrombotic therapy. The angiographic appearances at 3 months suggested that a local vasculitis may have been the precipitating cause.
We evaluated the loss of coronary collateral function in the absence of stimulation (disuse inhibition) by doubling the interval between successive left anterior descending coronary artery (LAD) occlusions in ponies in which collateral function initially had been enhanced by 2-min occlusions at 30-min intervals. Before collateralization, occlusion caused segment systolic shortening, velocity of shortening, and stroke work index in the LAD-dependent left ventricular apex to decrease, whereas heart rate and left ventricular end-diastolic pressure increased. After 476 +/- 102 occlusions, segment function recovered to preocclusion levels and hemodynamics were unchanged during occlusion. Occlusion did not elicit sustained functional deterioration until the occlusion interval was greater than or equal to 32 h. During the occlusion after the 128-h interval, segment systolic shortening, velocity of shortening, and stroke work index were reduced 69 +/- 8, 38 +/- 9, and 46 +/- 13%, respectively. Percent recovery of systolic shortening during successive occlusions declined exponentially (T1/e = 102.0 +/- 17.3 h). Thus, in ponies collateral function progressively declines when the occlusion interval is greater than or equal to 32 h, but complete inhibition does not occur even after 128 h without occlusion. This indicates that collateral function in ponies can be maintained by occlusions that are far less frequent than those needed for initial collateral development. The long time constant of collateral disuse inhibition suggests that equine collaterals are quite resistant to the effects of occlusion cessation and differ from canine collaterals in that respect.
Coronary collateral growth was stimulated in chronically instrumented conscious ponies by a previously validated intermittent coronary occlusion method. Changes in regional myocardial function (sonomicrometry) and reactive hyperemia (Doppler method) were used to monitor collateral growth and to program measurements of regional myocardial blood flow (microsphere method). A serial analysis of the transmural and lateral distributions of collateral blood flow was performed at the native and three superimposed levels of collateral growth. Results in nine animals undergoing an average of 553 +/- 188 brief coronary occlusions over 68 +/- 18 days demonstrated that as collateral conductance increased, the perfusion field within the ischemic region increased from the epicardium to the endocardium but not from the lateral edges to the center of the ischemic region. The findings are consistent with an analog model consisting of interarterial collaterals whose collective resistance is in series with arteriolar resistance of the recipient artery. No special protection of deeper myocardial layers by a subendocardial plexus or intramural collaterals was noted. Instead, the findings suggest that coronary extravascular compressive forces play a more important role than the transmural location of collaterals in determining the volume and spatial distribution of collateral blood flow during collateral growth in the pony.
BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) of the infarct-related artery was performed within 42 days of recombinant tissue-type plasminogen activator (rt-PA) administration in 1,414 of the 3,534 patients who participated in the Thrombolysis In Myocardial Infarction (TIMI) II study. Primary angiographic success was obtained in 88.7%, with bypass surgery within 24 hours in 3.3% and death within 24 hours in 0.7% of patients. By 1 year, 25.1% of the 1,414 patients had sustained one or more adverse outcomes including death (3.6%), reinfarction (8.4%), or the need for further revascularization (20%). METHODS AND RESULTS: Despite these generally favorable results, multivariate testing identified several anatomic and clinical subgroups as having an increased risk ratio (RR) for adverse outcome: Unsuccessful PTCA was more common in patients undergoing protocol-assigned PTCA within 2 hours of rt-PA administration (RR, 2.7; p less than 0.001) and in patients over age 70 years (RR, 1.7; p = 0.034). The need for further revascularization within 1 year was increased in the 30.4% of patients with multivessel disease (RR, 2.5; p less than 0.001), patients with prior angina (RR, 1.4; p less than 0.006), or those undergoing ischemia-driven PTCA within 15 hours of rt-PA administration (RR, 1.7; p = 0.022). The risk of death or recurrent infarction within 1 year was increased by the presence of multivessel disease (RR, 1.6; p = 0.007) or prior angina (RR, 1.5; p = 0.014). CONCLUSIONS: These observations do not necessarily apply to patients undergoing primary PTCA (or PTCA after other thrombolytic agents); however, they do offer a unique yardstick against which to evaluate the results of PTCA in myocardial infarction.
BACKGROUND: The Thrombolysis in Myocardial Infarction (TIMI) Phase II Trial randomized 3,339 patients to either an invasive (INV, n = 1,681) or a conservative (CON, n = 1,658) strategy after intravenous recombinant tissue-type plasminogen activator (rt-PA) for acute myocardial infarction. METHODS AND RESULTS: The patients assigned to the INV strategy routinely underwent cardiac catheterization, and when anatomically appropriate, percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting 18-48 hours after infarction. CON patients had these procedures only in response to the occurrence of spontaneous or provoked ischemia. One-year follow-up data are available in 3,316 patients (99.3%). The primary trial end point, death and nonfatal reinfarction, occurred in 14.7% of INV patients and in 15.2% of CON patients (p = NS). When analyzed individually, there was no difference (p = NS) in death (INV, 6.9%; CON, 7.4%) or recurrent infarction (INV, 9.4%; CON, 9.8%) between the two groups. Anginal status at 1 year was also similar. Cardiac catheterization and PTCA were performed more often in INV (98.0% and 61.2%, respectively) compared with CON (45.2% and 20.5%, respectively) patients. At 1 year, the cumulative number of patients who underwent coronary bypass surgery (INV, 17.5%; CON, 17.3%) was similar in the two groups. CONCLUSIONS: The INV and CON strategies resulted in similar favorable outcomes at 1 year of follow-up. In particular, the rates of mortality and reinfarction were not different and were impressively low in both groups. One possible advantage of the INV strategy was detected in subgroup analyses. In patients with a history of myocardial infarction, the data are suggestive that 1-year mortality was lower in INV patients (10.3%) than in CON patients (17.0%) (p = 0.03).
The aim of this study was to assess whether the incidence of early occlusion following angioplasty was greater among patients with unstable angina and whether the coronary lesions prone to early occlusion could be predicted from their angiographic appearance. Seventy-seven patients who had had a first angioplasty of a native vessel for stable or unstable angina in one twelve month period were included. The angiographic appearances of the angioplastied lesions were classified as either Type 1, which were smooth and unlikely to have thrombus or intimal rupture, or Type 2, which were irregular due to thrombus or intimal rupture. The lesion classification was compared to the patients' clinical features, i.e. stable or unstable angina, and the outcome of the angioplasty. Type 2 lesions occurred in 25% of patients with stable angina but 49% of patients with unstable angina (p less than 0.05). Early sudden occlusion of the angioplastied vessel occurred in 24% of patients with unstable angina but in only 3% of patients with stable angina (p less than 0.05) and in 6% of Type 1 lesions compared with 24% of Type 2 lesions (p less than 0.05). Thus it is possible to identify the clinical characteristics and angiographic appearances of those patients undergoing angioplasty who are most likely to experience early vessel occlusion.
The safety and efficacy of a new regimen of intravenous recombinant tissue-type plasminogen activator (rt-PA) potentially suitable for either pre- or in-hospital administration were assessed in 60 patients with acute myocardial infarction in an open label coronary angiographic study. The regimen consisted of a 20-mg bolus dose followed 30 min later by a delayed infusion of 80 mg over 2 h. This regimen was designed to facilitate prehospital administration of rt-PA. Infarct-related artery patency (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3 flow) was observed in 40 of 53 patients at 60 min (75.5%, 95% confidence intervals [CI] 61% to 84%) and in 55 of 60 patients at 90 min (91.7%, 95% CI 80% to 95%) after the rt-PA bolus. By 90 min the majority of patients (55%) exhibited TIMI grade 3 flow; infarct artery patency at 120 min was 84.9%. During hospitalization definite recurrent ischemia occurred in nine patients (15%); nonfatal recurrent infarction was noted in one (1.7%). Four patients (6.7%) experienced major bleeding, including one with intracranial bleeding. There were seven deaths (11.7%). Mortality was significantly influenced by the occurrence of cardiogenic shock, which was present in five patients at the time of enrollment. Blood fibrinogen levels were obtained before and during rt-PA infusion. At baseline and 30 and 150 min after the bolus dose, the mean fibrinogen level (+/- SD) was 284.83 +/- 77.39, 237.96 +/- 76.92 and 192.04 +/- 57.82 mg/dl, respectively. Compared with the baseline value, there was a significant (p less than 0.05) decrease in fibrinogen at both 30 and 150 min.(ABSTRACT TRUNCATED AT 250 WORDS)
To ascertain whether predischarge arteriography is beneficial in patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA), heparin and aspirin, the outcome of 197 patients in the Thrombolysis in Myocardial Infarction (TIMI) IIA study assigned to conservative management and routine predischarge coronary arteriography (routine catheterization group) was compared with the outcome of 1,461 patients from the TIMI IIB study assigned to conservative management without routine coronary arteriography unless ischemia recurred spontaneously or on predischarge exercise testing (selective catheterization group). The two groups were similar with regard to important baseline variables. During the initial hospital stay, coronary arteriography was performed in 93.9% of the routine catheterization group and 34.7% of the selective catheterization group (p less than 0.001), but the frequency of coronary revascularization (angioplasty or coronary artery bypass surgery) was similar in the two groups (24.4% versus 20.7%, p = NS). Coronary arteriograms showed a predominance of zero or one vessel disease (stenosis greater than or equal to 60%) in both groups (routine catheterization group 73.1%, selective catheterization group 61.3%). During the 1st year after infarction, rehospitalization for cardiac reasons and the interim performance of coronary arteriography were more common in the selective catheterization group (37.9% versus 27.6%, p = 0.007 and 28.6% versus 11.6%, p less than 0.001, respectively); however, the interim rates of death, nonfatal reinfarction and performance of coronary revascularization procedures were similar. At the end of 1 year, coronary arteriography had been performed one or more times in 98.9% of the routine catheterization group and 59.4% of the selective catheterization group (p less than 0.001), whereas death and nonfatal reinfarction had occurred in 10.2% versus 7.0% (p = 0.10) and 8.6% versus 9.0% (p = 0.87), respectively. Because the selective coronary arteriography policy exposes about 40% fewer patients to the small but finite risks and inconvenience of the procedure without compromising the 1 year survival or reinfarction rates, it seems to be an appropriate management strategy.
Studies were performed in the conscious pony instrumented with a Doppler flow probe and hydraulic occluder on the left anterior descending coronary artery (LAD), sonomicrometry crystals and intraventricular micromanometer in the left ventricle, and catheters in the left atrium and anterior interventricular vein. Two-minute LAD occlusions were performed every 30 min continuously or during working hours. Data on release of catabolites (potassium, hydrogen ions, and lactate) and norepinephrine from the initially dysfunctional region were obtained periodically during a regimen of 445 +/- 56 occlusions in six animals. Regional myocardial blood flow was measured (microsphere method) before and after an occlusion regimen in four animals. Marked release of catabolites and norepinephrine from the initially dysfunctional region was noted in association with early occlusions when myocardial segment function was severely reduced. With further occlusions, release of these substances decreased while segment function improved. Blood flow was markedly decreased in the initially dysfunctional region during an early occlusion but was at the control level during a later occlusion. Although the metabolic findings are consistent with protection due to "ischemic preconditioning" and no increase in collateral perfusion, the inverse relationship noted between catabolite release and segment function is best explained by flow-dependent mechanisms. These results, together with the myocardial blood flow data, serve to validate a previous assumption that protection against regional myocardial dysfunction under these conditions is due to increased collateral perfusion.
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To establish the magnitude of prehospital and hospital delays in initiating thrombolytic therapy for acute myocardial infarction, the time from telephone 911 emergency medical system (EMS) activation to treatment and its components were analyzed from eight separate ongoing trials. This included estimates of ambulance response time, prehospital evaluation and treatment time, and time from admission to the hospital to initiation of thrombolytic therapy. The average time from EMS activation to patient arrival at the hospital was prospectively determined to be 46.1 +/- 8.2 minutes in 3715 patients from eight centers. The time from admission to the hospital to initiation of thrombolytic therapy was retrospectively determined to be 83.8 +/- 55.0 minutes in a separate group of 730 patients from six centers. Both the prehospital and hospital time delays were much longer than those perceived by paramedics and emergency department directors. Shorter hospital time delays were observed in patients in whom a prehospital ECG was obtained as part of a protocol-driven prehospital diagnostic strategy and a diagnosis of acute infarction made before arrival at the hospital (36.3 +/- 11.3 minutes in 13 patients). These results show that the magnitude of time required to evaluate, transport, and initiate thrombolytic therapy will preclude initiation of treatment to most patients within the first hour of symptoms. Implementation of a protocol-driven prehospital diagnostic strategy may be associated with a reduction in time to thrombolytic therapy.
Myocardial bridging causing systolic occlusion of the left anterior descending coronary artery was identified in a 47-year-old man with angina. A fixed anterolateral wall defect was demonstrated on thallium imaging and he underwent successful division of the bridge resulting in abolition of his symptoms and disappearance of the thallium defect.
Given the many thrombolytic agents and the number of ways in which they can be combined with mechanical revascularization, the treatment of acute myocardial infarction has been the subject of active study and lively debate, which are likely to continue for some time. Several studies, including TIMI IIA (2,3,10,22), have suggested that immediate catheterization and angioplasty offer no clinical benefit and have a greater complication rate than a more delayed invasive strategy, but TIMI II (1) and SWIFT (16) trials have suggested that an even more conservative strategy of reserving catheterization and coronary angioplasty after thrombolytic therapy for patients with recurrent spontaneous or exercise-induced ischemia may be the most desirable approach for the majority of patients similar to those entered into these trials.
To assess the value and timing of percutaneous transluminal coronary angioplasty (PTCA) after thrombolytic therapy for acute myocardial infarction (AMI), 586 patients in the Thrombolysis in Myocardial Infarction Study Phase II-A were randomized among three treatment strategies, one using immediate coronary arteriography followed by PTCA if appropriate (immediate invasive strategy group, n = 195), a second that deferred angiography and PTCA for 18-48 hours (delayed invasive strategy group, n = 194), and a third, more conservative, approach in which PTCA was used only if ischemia occurred spontaneously or at the time of predischarge exercise testing (conservative strategy group, n = 197). Predischarge contrast left ventricular ejection fraction, the primary study end point, was similar among the patients in all three treatment groups and averaged 49.3%. The finding of a patent infarct-related artery at the time of predischarge arteriography was equally common among the patients in the three groups (mean, 83.7%); however, the mean residual infarct artery stenosis was greater in the patients in the conservative strategy group (67.2%) as compared with the patients in the immediate invasive (50.6%) and the delayed invasive strategy groups (47.8%) (p less than 0.001). Immediate invasive strategy led to a higher rate of coronary artery bypass graft surgery (CABG) after PTCA (7.7%) than did delayed invasive and conservative strategies (2.1% and 2.5%, respectively; p less than 0.01). Furthermore, among patients not undergoing CABG during the first 21 days, blood transfusion of more than 1 unit was used in 13.8% of the patients in the immediate invasive strategy group, 3.1% of the patients in the delayed invasive strategy group, and 2.0% of the patients in the conservative strategy group (p less than 0.001). At 1-year follow-up, the three treatment groups had similar cumulative rates of mortality (8.7%, pooled over all groups), fatal and nonfatal reinfarction (8.5%), combined death and reinfarction (14.5%), and CABG (17.2%), although the cumulative performance rate of PTCA remained higher in the invasive groups (immediate invasive strategy group, 75.8%; delayed invasive strategy group, 64.3%; and conservative strategy group, 23.9%; p less than 0.001). Thus, because conservative strategy achieves equally good short- and long-term outcome with less morbidity and a lower use of PTCA, it seems to be the preferred initial management strategy.
Because thrombus formation may contribute to coronary obstruction in patients with unstable angina pectoris, we performed a pilot investigation to determine whether thrombolytic therapy can relieve coronary narrowing in this acute ischemic syndrome. Sixty-seven patients with rest angina and angiographic evidence of coronary stenosis were randomly assigned to receive either low-dose intravenous recombinant tissue-type plasminogen activator (rt-PA) (0.75 mg/kg over 1 hour), high-dose intravenous rt-PA (0.75 mg/kg over 1 hour; total dose, 100 mg over 6 hours), or intravenous placebo followed by repeat coronary angiography at 24-48 hours to assess change in the severity of coronary narrowing. Each patient also received oral aspirin and intravenous heparin. Mean values of coronary stenosis severity (percent of diameter reduction) declined to a similar extent in each group: placebo, 75 +/- 14% to 72 +/- 14% (p = 0.07); low-dose rt-PA, 75 +/- 16% to 71 +/- 18% (p = 0.03), and high-dose rt-PA, 82 +/- 11% to 77 +/- 17% (p = 0.18), with only the low-dose rt-PA group achieving statistical significance. Resolution of intracoronary filling defects, increase in antegrade flow grade, or both also occurred equally among the three groups. There was considerable variation in individual patient response. Between 29% and 50% of patients within each group demonstrated a decrease in stenosis severity, whereas 50% to 57% noted either improvement in antegrade flow or resolution of intracoronary thrombus. There was no difference in incidence of major bleeding events among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Superior vena cava syndrome due to transvenous pacing leads is a rare event. We describe four cases. One occurred among 3,100 primary pacemaker insertions performed at our institution. In the other three cases the primary insertion had been performed elsewhere. Over 30 cases have been reported previously. Local infection, which preceded the development of superior vena cava syndrome in each of our four cases, and the presence of a severed retained lead, as in three of our cases, are important predisposing factors. There is no strong evidence that multiple lead insertion, if each lead remains intact, significantly increases the risk. The pathology at the site of obstruction includes thrombosis and in some cases fibrotic narrowing. Venous angiography is useful to show the site of obstruction, the extent of collateral circulation and to assess the response to treatment. Treatment should include removal of any infected pacemaker apparatus, anticoagulation and, if symptoms are of recent onset, thrombolytic therapy. Most patients improve but in those who do not angioplasty or surgical relief of the obstruction may be helpful.