Cost benefit for assessment of intermediate coronary stenosis with fractional flow reserve in public and private sectors in australia.

BACKGROUND: Fractional Flow Reserve (FFR) is a proven technology for guiding percutaneous coronary intervention (PCI), but is not reimbursed despite the fact that it is frequently used to defer PCI. METHODS: Costs incurred with use of FFR were compared in both the public and private sectors with the costs that would have been incurred if the technology was not available using consecutive cases over a two year period in a public teaching hospital and its co-located private hospital. RESULTS: FFR was performed on 143 lesions in 120 patients. FFR was < 0.80 in 37 lesions in 34 patients and 25 underwent PCI while 11 had CABG. It was estimated that without FFR 78 lesions in 70 patients would have had PCI with 17 patients having CABG with 35 additional functional tests. Despite a cost of $A1200 per wire, FFR actually saved money. Mean savings in the public sector were $1200 per patient while in the private sector the savings were $5000 per patient. CONCLUSIONS: FFR use saves money for the Federal Government in the public sector and for the Private Health Funds in the private sector. These financial benefits are seen in addition to the improved outcomes seen with this technology.

Apical sparing in tako-tsubo cardiomyopathy.

BACKGROUND: Tako-tsubo cardiomyopathy (TTC) is an acute reversible cause of segmental myocardial dysfunction that is poorly understood. We have noted a variant of this condition where a tiny segment at the apex retains some contractile function. This paper delineates the frequency of this variant relative to the classical form and the clinical differences between patients suffering from the two forms. METHODS: All cases of TTC (n = 35) were identified from our infarct angiography database and separated on the basis of apical sparing (n = 14) or no apical sparing (n = 21). RESULTS: Compared with the classical form, those with apical sparing were significantly younger (63 +/- 12 vs 72 +/- 13 years) and were more likely premenopausal (5/14 vs 0/21) and had higher ejection fractions (35 +/- 6% vs 32 +/- 4%). There was a trend towards higher recurrence (4/21 vs 0/14). There were no differences in time or season of presentation, precipitant stressor, premorbid drug therapy, haemodynamics at catheterization or acute outcomes. CONCLUSION: The apical sparing variant of TTC is common, accounting for 40% of cases. While the patients are younger and more likely premenopausal, there are no other distinguishing features between the classical and the variant form.

A primary stenting strategy as an alternative to fibrinolytic therapy in acute myocardial infarction. An analysis of results in hospital and at 6 weeks and 6 months.

OBJECTIVE: To report the feasibility and results to 6 months of a primary stenting strategy in patients with acute myocardial infarction (AMI). DESIGN: Prospective, single-centre, observational study. SETTING: A tertiary referral teaching hospital (Royal North Shore Hospital, Sydney), July 1997 to November 1998. SUBJECTS: 102 (of 194) consecutive patients presenting to the emergency department with AMI who were eligible for fibrinolytic therapy, and for a primary stenting strategy. The first 50 patients were under 70 years of age, and had not had previous coronary artery bypass grafting (CABG). The following 52 patients included patients up to 80 years and with previous CABG. OUTCOME MEASURES: Major adverse cardiac and cerebrovascular events: death, reinfarction, cerebrovascular accident (CVA) and repeat target lesion revascularisation, in hospital, and at 6 weeks and 6 months. Minor in-hospital adverse events: bleeding requiring blood transfusion, vascular complications and new-onset heart failure. Time delays to treatment, and duration of hospital stay. RESULTS: Normal flow was established in the infarct-related artery in 97/102 patients (95%). Stenting, percutaneous transluminal coronary angioplasty (PTCA), CABG or medical therapy was performed in 74, 11, 9 and 8 patients, respectively. Minor in-hospital events, time delays and hospital stay were similar to those reported previously. At 6 weeks, major adverse cardiac and cerebrovascular events had occurred in 5% of patients (four repeat target lesion revascularisation and one reinfarction). By 6 months, repeat target lesion revascularisation had been performed in an additional 10% of patients. No deaths had occurred. CONCLUSIONS: A primary stenting strategy can be performed safely, without significant delays and with excellent short and intermediate term outcomes.

Biochemical markers of acute myocardial infarction: strategies for improving their clinical usefulness.

We investigated the early diagnostic utility, including incremental value, of the serum cardiac markers creatine kinase (CK), CK-MB (mass and activity measurements), cardiac troponin T, and myoglobin in the diagnosis of acute myocardial infarction (AMI) in patients presenting to a major teaching hospital with chest pain and non-diagnostic electrocardiographs (ECG). The reference diagnosis of acute myocardial infarction was made by a single, independent cardiologist using World Health Organization criteria. CK and CK-MB mass were the only significant predictors of AMI at presentation to the Emergency Department. Logistic regression analysis revealed that CK did not significantly predict (P = 0.23) myocardial infarction once CK-MB mass was in the model. Using test results on follow up, in addition to presentation CK-MB mass, change in CK-MB mass was the only other significant independent predictor of AMI. Likelihood ratios for various levels of the significant markers in the logistic regression are given. In conclusion, CK-MB mass measurement was the only useful serum cardiac marker for the diagnosis of AMI in patients presenting with chest pain with non-diagnostic ECGs.

A randomized comparison of intravenous heparin with oral aspirin and dipyridamole 24 hours after recombinant tissue-type plasminogen activator for acute myocardial infarction. National Heart Foundation of Australia Coronary Thrombolysis Group.

BACKGROUND: This study addressed the need for heparin administration to be continued for more than 24 hours after coronary thrombolysis with recombinant tissue-type plasminogen activator (rt-PA). METHODS AND RESULTS: A total of 241 patients with acute myocardial infarction were treated with 100 mg rt-PA and a bolus of 5,000 units i.v. heparin followed by 1,000 units/hr i.v. heparin for 24 hours. At 24 hours, 202 patients were randomized to continue intravenous heparin therapy (n = 99) in full dosage or to discontinue heparin therapy and begin an oral antiplatelet regimen of aspirin (300 mg/day) and dipyridamole (300 mg/day) (n = 103). On prospective recording, there were no differences in the pattern of chest pain, reinfarction, or bleeding complications. Coronary angiography on cardiac catheterization at 7-10 days showed no differences in patency of the infarct-related artery. The proportion of patients with total occlusion (TIMI grade 0-1) of the infarct-related artery was 18.9% in the heparin group and 19.8% in the aspirin and dipyridamole group. In the patients with an incompletely occluded infarct-related artery, the lumen was reduced by 69 +/- 2% of normal in the heparin group and 67 +/- 2% in the aspirin and dipyridamole group. Left ventricular function assessed on cardiac catheterization and radionuclide study at day 2 and at 1 month showed no differences between the two groups. Left ventricular ejection fraction on radionuclide ventriculography at 1 month was 52.4 +/- 1.2% in the heparin group and 51.9 +/- 1.2% in the aspirin and dipyridamole group. CONCLUSIONS: We conclude that heparin therapy can be discontinued 24 hours after rt-PA therapy and replaced with an oral antiplatelet regimen without any adverse effects on chest pain, reinfarction, coronary patency, or left ventricular function.

Determinants of recurrent ischaemia and revascularisation procedures after thrombolysis with recombinant tissue plasminogen activator in primary coronary occlusion.

This paper reports the immediate effects of thrombolysis and their subsequent influence on revascularisation procedures and clinical outcome over the subsequent twelve months. Coronary arteriography was performed at 21 days on 131 of 145 patients who received recombinant tissue plasminogen activator (n = 68) or placebo (n = 63) within 2.5 hours of symptom onset after primary coronary occlusion. Patency rates (TIMI grades 2 and 3) of the infarct-related artery were 81% with plasminogen activator and 63% with placebo (P = 0.02). Early (within 21 days) angiography for recurrent ischaemia was necessary in 31 (21%) patients (20 plasminogen activator, 11 placebo NS) and definite reinfarction occurred in 8 (5%) patients (4 plasminogen activator, 4 placebo). During one year follow-up without planned secondary intervention, coronary artery bypass grafting was more frequent in patients who had received thrombolytic therapy (23% plasminogen activator, 4% placebo P = 0.001); coronary angioplasty procedures were similar in both groups (12% plasminogen activator, 11% placebo NS). Mortality at 21 days was 5% (4 plasminogen activator, 4 placebo) and at one year was 7% (5 plasminogen activator, 5 placebo). Logistic regression analysis identified models comprising characteristics predictive of subsequent bypass grafting (plasminogen activator, multivessel disease, occluded infarct-related artery) and coronary angioplasty (non-q wave infarction, severe (91-99%) residual stenosis, left anterior descending infarct-related artery). Initial non-q wave infarction was the only predictor of early recurrent ischemia (odds ratio 4, P = 0.02) irrespective of residual stenosis severity.

Short-term and long-term benefits of coronary angioplasty in unstable angina pectoris.

Primary coronary angioplasty was attempted in 288 patients (206 men and 82 women) who presented with stable (50%) or unstable (50%) angina pectoris. The success rates of angioplasty and the subsequent revascularization requirements in these two angina categories were compared during a one year prospective follow-up. The site and distribution of coronary artery stenoses did not differ between the categories. Three hundred and five dilatations were attempted (149 in 144 patients with unstable angina and 156 in 144 patients with stable angina). Of these procedures, 265 (87%) were technically successful--133 (89%) in 128 patients with unstable angina and 132 (85%) in 120 patients with stable angina. Lower success rates were achieved in 29 attempted dilatations of vessels with chronic total occlusion (19 successful [66%], P = 0.002) and in 19 patients who presented with unstable angina after recent (within two weeks) infarction (10 patients with successful angioplasty, [53%], P less than 0.0001). Subsequent revascularization requirements after an initially successful angioplasty in 57 patients were greater in unstable (36 patients) than in stable angina (21 patients; P = 0.05) and reflected the greater frequency of repeat angioplasty in patients with unstable angina (22 patients) compared with those with stable angina (10 patients; P = 0.04) among patients with recurrent symptoms. At one year, 245 patients (85%)-121 treated for unstable angina and 124 treated for stable angina--experienced no angina during normal daily activities. We conclude that a primary angioplasty success rate of 89% can be achieved in patients with unstable angina pectoris but this rate is significantly lower in patients presenting after recent infarction. Repeat angioplasty for recurrent symptoms after a successful primary procedure is required more frequently in patients presenting with unstable angina.

Late (one month) reversible ischaemia after primary coronary occlusion treated with recombinant tissue plasminogen activator (rTPA).

The incidence of reversible ischaemia was assessed four weeks after primary coronary occlusion in 36 patients who had not required earlier revascularisation after randomisation to receive rTPA (n = 19) or placebo (n = 17). Coronary arteriography was performed at three weeks and thallium scintigraphy with dynamic stress testing at four weeks. Patients were followed for one year without planned intervention in the absence of symptoms. Managing physicians remained blinded to thrombolytic therapy. Patency rate of the infarct related artery at three weeks was greater after rTPA (rTPA 16, placebo 9; p = 0.04). Reversible perfusion defects within infarct related artery territory occurred with similar frequency in both treatment groups (rTPA 7, placebo 8). Multivessel disease was frequent (rTPA 11, placebo 12) but associated with a low incidence of reversible perfusion defects outside infarct related artery territory (rTPA 3, placebo 2). Thallium scintigraphy identified six of seven patients requiring subsequent revascularisation (sensitivity 86%, specificity 59%, negative predictive value 94%). Dynamic stress testing was positive for reversible ischaemia in 28% (rTPA 6, placebo 4) and identified two patients requiring revascularisation (sensitivity 29%, specificity 72%, negative predictive value 81%). The greater patency rate achieved with rTPA at three weeks after primary coronary occlusion was not associated with a significantly greater incidence of reversible perfusion defects at four weeks in patients who had not required prior revascularisation. The absence of reversible perfusion defects at four weeks was associated with a low incidence of revascularisation procedures during one year follow-up.

Comparison of the immediate and long-term effects of captopril and isosorbide dinitrate as adjunctive treatment in mild heart failure.

1. The efficacy of captopril and isosorbide dinitrate (ISDN) as adjunctive therapy to digoxin and diuretics in mild heart failure was compared in a double-blind study. 2. Twenty-one patients were randomly allocated to captopril (twice or three times daily) or ISDN. Eighteen patients completed a protocol of placebo run-in, dose titration and maintenance treatment for 3 months. 3. Symptom-limited exercise tolerance, ejection fraction and radionuclide indices of diastolic function estimated by gated blood pool scan did not change with either treatment. 4. Captopril improved functional class (Canadian Cardiovascular Society) and reduced requirements for increased diuretic dosage at both 1 and 3 months of maintenance treatment. Patients treated with ISDN required increased diuretic and did not improve their functional class. Differences between the treatments were significant only for diuretic dosage requirements. 5. We conclude that adjunctive therapy of mild heart failure with captopril administered twice daily provides a diuretic-sparing effect and may improve functional class during 3 months of maintenance treatment.

Sympathetic (alpha-beta) or calcium channel blockade for hypertensive myocardial infarction? A haemodynamic comparison of labetalol and nifedipine.

The haemodynamic impact of alpha- and beta-adrenoceptor blockade (labetalol) was compared with that of slow-calcium channel blockade (nifedipine) in 32 patients with sustained elevation of systemic arterial pressure (systolic blood pressure greater than 160; diastolic blood pressure greater than 95 mmHg) following a recent myocardial infarction (6-22 h). Patients with normal (pulmonary artery occluded pressure; (PAOP less than 18 mmHg; n = 16) or impaired (PAOP greater than 18 mmHg; n = 16) left ventricular function were randomized to labetalol (1 mg/kg i.v. 15 min) or nifedipine (20 mg sublingually) and haemodynamic profile was measured over 2 h. Both drugs equally reduced mean systemic arterial pressure (P less than 0.01 versus pretreatment control), and presumably left ventricular afterload; however, the heart rate (P less than 0.01) and cardiac index (P less than 0.01) increased after nifedipine, contrasting with reductions in both variables following labetalol (P less than 0.01). The elevated left ventricular filling pressure was reduced by both labetalol (P less than 0.05) and nifedipine (P less than 0.01) but the reduction was greater following nifedipine (-2 mmHg versus -5 mmHg, P less than 0.05). Thus both compounds were equally effective hypotensive agents. Labetalol consistently reduced cardiac stroke work and double product, important determinants of myocardial oxygen requirements; however, nifedipine afforded some improvement in cardiac performance in patients with left ventricular dysfunction.

A clinical model for predicting survival following acute myocardial infarction in patients without cardiogenic shock: a multivariate (Cox) analysis.

A multivariate predictive model for early (six-month) survival based on Cox's proportional-hazards regression model was developed using data collected prospectively from 317 consecutive patients admitted with acute myocardial infarction to a coronary care unit (CCU). Of these, 63 (19.8%) died within the follow-up period. Patients with cardiogenic shock were excluded from the study. Variables associated with survival were sought from clinical, historical, electrocardiographic and radiographic variables recorded at the time of admission. On multivariate analysis, a stepwise selection procedure identified four variables which described the probability of survival for the six-month follow-up. These were: age, upper lung crepitations, marginal and also definite radiographic cardiomegaly on an anteroposterior radiograph. With this combination of clinical variables alone, using a survival probability partition value of 80%, the model had a sensitivity of 67% and a specificity of 75%. However, the model's predictive accuracy for death was 40%, compared to a predictive accuracy for survival of 90%. This clinical model is most useful for early discrimination of those patients at low risk of death within six months of CCU admission. Other predictive tests for premature death would need to exceed these discriminatory criteria to justify their cost and risks.

Haemodynamic dose-response effects of a transdermal nitrate delivery system in acute myocardial infarction with and without left heart failure.

The haemodynamic effects of a transdermal nitroglycerin delivery system (NTG-TTS) were investigated in 67 patients with a recent myocardial infarction. The study objectives were to define the dose-response effects of NTG-TTS and to examine the influence of baseline haemodynamic status on subsequent response. Therefore, patients with normal cardiac function [pulmonary artery occluded pressure (PAOP) less than 18 mm Hg, n = 40] and those with acute heart failure (PAOP greater than 18 mm Hg, n = 27) were studied after one of three regimens (TTS-10, TTS-20, or TTS-40) with the intention of securing 10 evaluable patients in each group. In patients with acute heart failure, all three doses reduced the left ventricular filling pressure with a modest decrease in systemic arterial pressure; cardiac index and heart rate were unaltered. The systemic vascular resistance was significantly reduced from 120 min. In patients with normal left ventricular function, there were small but significant reductions in systemic arterial pressure and vascular resistance with limited increases in heart rate; the cardiac stroke work index was reduced. These results are compatible with actions of NTG-TTS mainly on capacitance vessels; PAOP fell with limited impact on systemic arterial pressure and vascular resistance index. This mode of nitrate delivery resulted in a low incidence of hypotension and side-effects; comparison with other delivery methods in myocardial infarction seems indicated.

Physical characteristics and clinical evaluation of a new disposable fibreoptic transducer-tipped catheter system.

A new disposable fibreoptic transducer-tipped catheter manometer system was evaluated to assess its accuracy, stability of accuracy under prolonged simulated intra-arterial conditions, and dynamic characteristics. Maximum errors observed in the measurement of static pressure using a sample of five catheters (with one display unit) were 2 mmHg at 0 mmHg reference pressure, 2 at 20 mmHg, 4 at 40 mmHg, 4 at 100 mmHg and 9 at 200 mmHg. An immersion artifact caused a shift in baseline of up to 2 mmHg. Exposure of the transducer to 24 hours of simulated intra-arterial conditions (pulsatile pressure at 40 degrees C) resulted in errors of up to 7 mmHg for pressures up to 100 mmHg, and 11 mmHg for 200 mmHg, which were largely attributable to a drift in baseline pressure (up 6 mmHg by 24 hours). Consistent overestimation by the system suggested inappropriate gain setting within the display unit which, however, is not user-adjustable. The system exhibited uniform frequency response up to 33 Hz.

First-line treatment of left ventricular failure complicating acute myocardial infarction: a randomised evaluation of immediate effects of diuretic, venodilator, arteriodilator, and positive inotropic drugs on left ventricular function.

A prospective randomised trial compared the immediate haemodynamic effects of intravenous diuretic (frusemide), venodilator (isosorbide dinitrate), arteriolar dilator (hydralazine), and positive inotropic stimulation (prenalterol) as first-line therapy for acute left ventricular (LV) failure following myocardial infarction. Forty-eight patients with transmural myocardial infarction and a pulmonary artery occluded pressure (PAOP) of greater than 20 mm Hg were studied within 18 h of admission to a coronary care unit. Both frusemide (-4 mm Hg; p less than 0.01) and isosorbide dinitrate (-6 mm Hg; p less than 0.01) reduced LV filling pressure without change in cardiac index and heart rate. Although both hydralazine and prenalterol increased cardiac index (p less than 0.01), the reduction in LV filling pressure (-2 mm Hg; p less than 0.05) was less than with frusemide and isosorbide dinitrate, and was associated with an increased heart rate (+8 and +13 beats min-1; p less than 0.01). These data suggest that in acute heart failure following myocardial infarction the four treatment modalities could be ranked in descending order of potential benefit as follows: venodilatation (isosorbide dinitrate)--decrease of LV pressure/work; diuretic therapy (frusemide)--decrease of LV pressure/work offset by a transient pressor effect; arteriolar dilatation (hydralazine)--decrease of LV pressure/work and of PAOP, but offset by tachycardia; and positive inotropic therapy (beta 1-agonist prenalterol)--tachycardia and augmented LV afterload. Combination of the former and latter agents, because of their differing modes of action, should offer haemodynamic advantages over monotherapy and deserves further evaluation.

Nifedipine following acute myocardial infarction--dependence of response on baseline haemodynamic status.

The haemodynamic effects of nifedipine (20 mg sublingually) were studied in 40 patients with acute myocardial infarction within 18 h of the onset of symptoms. To determine the influence of preload and afterload on the haemodynamic response to nifedipine, patients were prospectively stratified equally into four groups of 10 patients based on systemic blood pressure level (less than or greater than 160/100 mm Hg) and level of left ventricular filling pressure [pulmonary artery-occluded pressure (PAOP) less than or greater than 18 mm Hg]. In all groups, nifedipine reduced systemic arterial pressure (p less than 0.01) and vascular resistance index (p less than 0.01); heart rate (p less than 0.01) and cardiac index (p less than 0.01) were increased. PAOP was reduced by nifedipine only in those hypertensive patients in whom it was initially raised; in these patients cardiac stroke volume index also increased (p less than 0.01). In hypertensive patients with normal PAOP the cardiac stroke work index was reduced. In patients with normal systemic and pulmonary arterial pressures, nifedipine had no beneficial effects on cardiac function. These data suggested that haemodynamic criteria may allow selection of patients for nifedipine therapy following myocardial infarction; clear advantages were evident only in hypertensive patients in both the presence and the absence of left ventricular failure.

Haemodynamic dose-response effects of intravenous indoramin in acute heart failure complicating myocardial infarction.

The haemodynamic dose-response effects of intravenous indoramin were evaluated in 12 patients with acute heart failure (pulmonary artery occluded pressure of greater than 20 mm Hg) complicating a recent myocardial infarction. Following a 1-h control period with confirmed stable haemodynamics, the effects of three intravenous bolus doses of indoramin (0.125, 0.125, and 0.25 mg/kg at 15-min intervals) were determined in the 10- to 15-min period following each intravenous injection. Plasma drug concentrations rose with the administered dose and were in the previously established therapeutic range. Ten patients tolerated all three doses of the drug; two patients were withdrawn following the second dose owing to clinically evident hypotension (systolic blood pressure of less than 100 mm Hg). Indoramin resulted in progressive falls in systolic, diastolic, and mean systemic arterial pressures (p less than 0.01) without change in cardiac index. There was a dose-related reduction in the heart rate (0.5 mg/kg; -7 beats/min; p less than 0.01). The left ventricular filling pressure showed a significant and quadratic reduction over the dose range (0.5 mg/kg, -5 mm Hg; p less than 0.01). The systemic vascular resistance index was reduced (-333 dynes X s X cm-5 X m2; p less than 0.001) and the stroke volume index increased (+3 ml/m2; p less than 0.05) following the maximum cumulative dosage. These data established the therapeutic safety of indoramin (0.125-0.5 mg/kg) in acute heart failure following myocardial infarction. An improvement in cardiac performance in these patients was compatible with circulatory actions on both cardiac preload and afterload.

Haemodynamic advantages of a combined inotropic/venodilator regimen over inotropic monotherapy in acute heart failure.

The haemodynamic influence of positive inotropic therapy with dobutamine, both alone and when combined with isosorbide dinitrate, was evaluated in 10 consecutive patients admitted to Coronary Care with acute left ventricular failure (pulmonary artery occluded pressure greater than 20 mm Hg) complicating myocardial infarction. Dobutamine increased systemic arterial blood pressure and heart rate without reduction in the left heart filling pressure; cardiac index (+0.9 L/min/m2; p less than 0.01) was substantially increased. Thus, consequent on these effects, dobutamine could increase myocardial oxygen requirements. The addition of intravenous isosorbide dinitrate reduced systemic arterial pressure and left heart filling pressure; the augmented cardiac index following therapy with dobutamine alone was maintained. Combined dobutamine/nitrate therapy, therefore, appeared haemodynamically superior to dobutamine monotherapy, in that it improved cardiac stroke volume at a normalised left ventricular filling pressure. These data suggest that combined dobutamine/nitrate therapy may prove useful as an adjunct to the treatment of normotensive heart failure complicating acute myocardial infarction.

The effects on left ventricular performance of verapamil and metoprolol singly and together in exercise-induced angina pectoris.

Concurrent therapy with the calcium channel blocker, verapamil, and the beta-blocking group of compounds is usually felt to be clinically contraindicated due to the former's potent dromotropic and negative inotropic actions. The basis of this assumption was examined in a rest and exercise hemodynamic study of the effects of verapamil and the cardioselective beta-blocking drug, metoprolol, in 22 patients with stable angina pectoris and angiographically confirmed coronary artery disease. In a randomized study, 11 patients were assessed following intravenous verapamil (16 mg) alone, 11 following intravenous metoprolol (10 mg) alone, and all 22 were assessed on combination therapy. The plasma levels achieved at the time of each hemodynamic assessment were in the therapeutic range. At rest, verapamil alone significantly lowered systemic arterial pressure and vascular resistance; metoprolol alone lowered heart rate and increased systemic vascular resistance without change in systemic arterial pressure. Combination therapy reduced systemic arterial pressure and heart rate without change in cardiac output and systemic vascular resistance. During upright bicycle exercise, the changes were directionally similar. Depression of cardiac function (i.e., reduced cardiac output at increased pulmonary artery occluded pressure) occurred following metoprolol but not following verapamil; the addition of verapamil did not accentuate the depression of function induced by metoprolol. These results suggested that in patients with stable coronary artery disease, without manifest conduction system abnormality, the cardiac depressant actions of verapamil were countered by its vasodilator properties.(ABSTRACT TRUNCATED AT 250 WORDS)