Direct coronary stenting versus stenting with balloon pre-dilation: incidence of enzyme release and follow-up results of a multicentre, prospective, randomized study. The CK and Troponin I Estimation in direct STenting (CK TEST) trial.

AIM: The aim of this study was to assess the safety of direct coronary stenting, its influence on costs, duration of the procedure, radiation exposure, clinical outcome and the incidence of periprocedural myocardial damage as assessed by enzyme release determination. METHODS: We randomized 103 patients (109 lesions) to direct stent implant or stent implant following balloon predilatation. Patients with heavily calcified lesions, bifurcations, total occlusions, left main lesions and very tortuous vessels were excluded. Three samples of blood were drawn; before, 12 and 24 h after the procedure and total CK, CK MB mass and troponin I determination was carried out in a single centralized laboratory. RESULTS: Direct stenting was successful in 62/62 lesions (100%). No single loss or embolization of the stent occurred. All stents in the group with predilatation were effectively deployed. The immediate post procedure angiographic results were similar with both techniques. Contrast media consumption and procedural time were significantly lower in direct stenting (150+/-82 cc and 30+/-13 min) than in pre-dilated stenting (184+/-85 cc and 36+/-14 min) (P=0.04 and P=0.036 respectively) while fluoroscopy time was similar (9.1+/-12 vs 9.19+/-15 min, P=0.97). The incidence of enzyme release was similar in the groups with only three non Q MI all in the pre-dilated group (P=0.149). Any elevation of CK MB and troponin I occurred in 7% of direct stent vs 12% of pre-dilated group (P=0.66), isolated troponin I elevation in 21% of both groups. Major adverse cardiac events during hospitalization were 0 in direct and 3 in pre-dilated stenting (P=0.66), but there were no significant differences at follow-up at 1, 6 and 12 months between the 2 groups (target lesion revascularization at 12 months 11 vs 14% in the 2 groups respectively). CONCLUSION: Direct stenting is as safe as pre-dilated stenting in selected coronary lesions. Acute results and myocardial damage as assessed by enzyme release determination are similar, but procedural costs (as measured by resource consumption) and duration of the procedure are lower in direct stenting. Overall success rate and mid-term clinical outcome are similar with both techniques.

Subcutaneous enoxaparin following thrombolysis and intravenous unfractionated heparin in ST-elevation acute myocardial infarction: safety and efficacy of low vs full dose.

AIM: In ST-segment elevation myocardial infarction (STEMI) treated with fibrin-specific thrombolytic agents, early intravenous unfractionated heparin (UFH) is warranted. Low molecular weight heparin Enoxaparin currently represents an alternative to UFH, to be used until hospital discharge. Since optimal dosing of subcutaneous Enoxaparin is not standardized, we conducted an observational study to compare safety and efficacy of low (4,000 U once daily) vs full dose (100 U/kg twice daily) regimens. METHODS: All STEMI patients successfully treated with tenecteplase and intravenous UFH and referred to the Catheterization Laboratory between June 2002-November 2003 for predischarge coronary angiography, were evaluated. The primary end-point was the composite of hemorrhages and residual angina/reinfarction during Enoxaparin administration, whereas secondary end-points were occurrence of venous thromboembolism (VTE) during Enoxaparin administration, and infarct-related artery (IRA) patency rate at predischarge coronary angiography. RESULTS: Out of 123 patients, 57 (M/F 45/12, mean age 65.8+/-8.1 years) received low dose, and 66 (men/women 45/21, mean age 62.6+/-11.8 years) full dose subcutaneous Enoxaparin. The incidence of the composite primary end-point was comparable in both groups (19% vs 26%; P=NS). Also, null was the occurrence of VTE, whereas the IRA patency rate did not significantly differ in the 2 groups (84% vs 86% TIMI 3 and 11% vs 9% TIMI 2 flow grades; P=NS). CONCLUSIONS: In patients with STEMI undergoing successful recanalization with tenecteplase and intravenous UFH, low dose subcutaneous Enoxaparin appears preferable to full dose, in the light of comparable safety and clinical efficacy and superior easiness of use.

Dose and test for dipyridamole infusion and cardiac imaging early after uncomplicated acute myocardial infarction.

To evaluate the relation of the dose of intravenous dipyridamole on results of thallium and echocardiographic testing, the results of standard- (0.56 mg/kg/4 minutes) versus high- (0.84 mg/kg/10 minutes) dose dipyridamole were obtained 9 +/- 3 days after uncomplicated acute myocardial infarction in 57 patients. New wall motion abnormalities were compared with redistribution of thallium imaging and results of discharge coronary angiography. The sensitivity of thallium in predicting the presence of multivessel coronary artery disease was significantly (p < 0.01) higher (85%) than echocardiography (53%) and was unaffected by the dose. However the sensitivity of echocardiography was better with the higher dose (53 vs 14%). Minor adverse effects occurred in 34 patients (59%) after receiving the high dose and only in 4 patients (7%) after the standard dose (p < 0.001). Thus, thallium-201 scintigraphy during standard-dose dipyridamole infusion is more effective than high-dose dipyridamole echocardiographic testing in safely identifying patients who could benefit from early invasive evaluation and therapy.

The magnitude of the benefit from preCCU thrombolysis in acute myocardial infarction: a long term follow up.

OBJECTIVE: Our aim was to determine the relationship among the time saved by administration of thrombolytic therapy in prehospital versus hospital setting and long term mortality; number, duration of hospitalizations and their causes. BACKGROUND: There is much theoretic, experimental and trial evidence to indicate that in acute myocardial infarction the earlier the thrombolytic therapy is given, the greater its efficacy. However, the clinical importance of this gain time in long term is still uncertain. SUBJECTS: 280 patients with suspected acute myocardial infarction in perspective, controlled study with two parallel groups of consecutive patients without contraindication for thrombolysis, who were seen by general emergency physicians before hospitalization (Gr.1) or later in hospital by the attending cardiologist (Gr.2). The main outcomes measured was mortality rate at 5 years, causes, number and duration of new hospitalizations. RESULTS: The median pain to needle time was 90' (25 degrees percentile:67'; 75 degrees percentile:165') in Gr.1 vs 165' in Gr.2 (25 degrees percentile:110'; 75 degrees percentile:225'). The median time difference was 75' (P<0.001). The 35th day total mortality rate was 7.5% and 10.6% (p:n.s.) in Gr.1 vs Gr.2 respectively, 8.6% (Gr.1) vs 19.7% (Gr.2) (P<0.015) at 1 year, and 19.2% (Gr.1) vs 47.2% (Gr.2) (P<0.015) at 5 years. The percentage of patients with a number of new hospitalizations greater than 1 during 5 years was not significantly different in Gr.1 vs Gr.2 (44.1% vs 48.35, p:n.s.). The total duration of hospitalization was 479 days in Gr.1 vs 1431 days in Gr.2 (P<0.001). The 75 Gr.1 patients alive at the end of 5 years follow up had a mean hospital stay of 3.86+/-5.92 days vs 8.05+/-16.60 days (P<0.036) of the 94 Gr.2 patients alive after 5 years. The total and mean stay for recurrence of acute MI was significantly different in Gr.1 vs Gr.2 (90 vs 425 days: P<0.001; and 13+/-6.2 days vs 25+/-5.4: P<0.003 respectively). Cardiac failure led to the 1.16% in Gr.1 vs 9.43% of new admission (P<0.028) for a total of 57 vs 243 days in Gr.1 and Gr.2 respectively (P<0.001). Cumulative mortality rate for any cause at 5 years was 19.2% and 47.2% in prehospital and in hospital treated patients (P<0.015), obtaining diverging survival curves. CONCLUSIONS: The magnitude of the benefit from earlier thrombolysis is such that giving thrombolytic treatment earlier is the main problem to reduce the time from onset of symptoms to reperfusion, to salvage myocardial muscle and obtain diverging survival curves.

Effects of coronary artery revascularization and perioperative myocardial infarction on left ventricular wall motion.

The effects of coronary artery revascularization and perioperative myocardial infarction on left ventricular wall motion are still controversial. In this study perioperative myocardial infarction was quantitatively estimated with the cumulative activity of the CK-MB isoenzyme in the perioperative period in a group of 77 consecutive patients undergoing coronary artery bypass surgery. After the operation (on average 9 +/- 1.8 months) all the patients were submitted to left ventricular and coronary angiography. Overall the global left ventricular ejection fraction was unchanged after the operation. The subgroup of patients with all patent grafts showed an improvement of both regional wall motion (P less than 0.05) and ejection fraction (from 58 +/- 13 to 64 +/- 13%, P less than 0.005); the number of angiographically abnormal left ventricular segments decreased from 28.5 to 16.6% (P less than 0.001). The cumulative activity of CK-MB enzyme was significantly correlated with the pre- and postoperative changes of ejection fraction (r = -0.51, P less than 0.01). Thus coronary artery bypass surgery can improve regional wall motion, but the likely benefit is observed in the absence of a perioperative myocardial ischemic damage.

Noninvasive prediction of restenosis after coronary angioplasty: a head to head comparison among exercise ECG, dipyridamole and exercise thallium scintigraphy.

Restenosis remains the main limitation of percutaneous transluminal coronary angioplasty (PTCA). Since it seems likely that restenosis not severe enough to induce ischemia may be better detected with pharmacological testing than with exercise, we investigated whether dipyridamole thallium scintigraphy is better than exercise-electrocardiogram and exercise-thallium in predicting restenosis after PTCA. Noninvasive tests and re-angiography were performed in 61 consecutive patients, 5-6 months after successful single vessel PTCA. Detection of vessel stenosis greater than or equal to 50% was used as angiographic criteria for restenosis. Exercise-induced angina, ST segment depression greater than or equal to 1 mm at exercise-electrocardiogram and reversible perfusion defects in the area supplied by the dilated vessel, during either dipyridamole and exercise-thallium, were considered noninvasive abnormal responses. The overall restenosis rate was 41% (25/61). Angina was the most specific (97%) of all criteria for restenosis, but also one of the least sensitive (40%), slightly better than exercise-ECG (24%). Exercise-thallium had lower sensitivity (72% vs 88%, p less than 0.05) and negative predictive value (82% vs 91%, p less than 0.05) than dipyridamole-thallium. In patients positive at both exercise-thallium and dipyridamole-thallium testing, mean stenosis at follow-up was more severe (73 +/- 23%) than in patients with positive dipyridamole-thallium and negative exercise-thallium (55 +/- 26%) results, but the difference did not reach statistically significant levels. For these reasons, dipyridamole-thallium seems to be an acceptable alternative to exercise thallium to follow patients after initially successful PTCA.

Nifedipine compared with verapamil in unstable angina pectoris.

A randomized trial was performed in 22 patients with unstable angina to compare the efficacy of oral verapamil with nifedipine in reducing symptomatic ischaemic episodes. The trial consisted of a 48 h control period, a 96 h treatment period with nifedipine (20 mg every 6 h) or verapamil (120 mg every 6 h), and a follow-up period. Patients who had a minimum of four symptomatic ischaemic episodes during the control period were entered into the trial. Asymptomatic ischaemic episodes were evaluated by Holter monitoring. Coronary angiography was performed at the end of the treatment period. Both nifedipine and verapamil significantly reduced the mean number of daily symptomatic ischaemic episodes (p less than 0.01) and the total number of ischaemic episodes (p less than 0.03). This study confirmed the high degree of efficacy of both nifedipine and verapamil in reducing the number of ischaemic episodes during short-term treatment of unstable angina. Nevertheless, a significant number of myocardial infarctions occurred in these patients, and some required subsequent coronary bypass graft operations.

Enoxaparin for the treatment of acute myocardial infarction with persistent ST-segment elevation.

Enoxaparin (E) is a low-molecular-weight heparin which has been proven more effective than unfractionated heparin (UFH) for the treatment of non-ST-segment elevation acute coronary syndromes. Limited and inconclusive on the other hand, are the data on the use of E in acute myocardial infarction with persistent ST-segment elevation (STEAMI). Therefore, we performed a review of the literature in order to evaluate the level of evidence relative to the efficacy and safety of E in such a clinical setting. The effect of E in STEAMI has been evaluated in 7 clinical studies, including a total of about 9500 patients. Compared to placebo, E resulted more effective on the incidence of the combined end-point of death, re-infarction and recurrent angina in the study by Glick et al. and on the patency of the infarct-related artery in the AMI-SK study. Compared to UFH, E resulted more effective on the incidence of the combined end-point of death, reinfarction and unstable angina in the study by Baird et al. and of in-hospital re-infarction and refractory ischemia rates in both ASSENT-3 and ASSENT-3 PLUS, while the effect on the patency of the infarct-related artery, which was evaluated in HART-II and ENTIRE-TIMI 23, resulted non univocal. Overall, bleeding complications were more frequent than with placebo and comparable to UFH, with the exception of ASSENT-3 PLUS where pre-hospital administration of E was associated with a doubled incidence of intracranial bleeding (although only in patients older than 75 years). In conclusion, the administration of E, in association with aspirin and thrombolytics, already appears a possible therapeutic option for the treatment of STEAMI, due to its good efficacy and safety profile, along with its easiness of use. However, prior to have its use recommended, the current B level of evidence of a superior efficacy and safety compared to UFH needs to be reinforced. Further-more, some open issues relative to the use of E in particular settings (aged patients, in association with glycoprotein IIb/IIIa inhibitors and during percutaneous coronary revascularization) need to be clarified.

[Angiographic aspects of unstable angina]. / Aspetti angiografici dell'angina instabile.

One-hundred and ninety-four patients with unstable angina pectoris (91 "in crescendo" angina and 103 new onset angina) underwent coronary angiography. The angiographic data from both groups were compared in order to discover whether angiographic aspects were related to the various clinical symptoms of coronary artery disease. Patients with recent onset angina had a significant increase (p less than 0.0001) of mono-vessel disease, whereas multi-vessel disease was prevalent in patients with "in crescendo" angina pectoris. Higher prevalence of coronary collaterals was observed in patients with "in crescendo" angina (p less than 0.005). No significant difference was observed in ejection fraction of the two groups. A further analysis was performed in 100 patients with unstable angina pectoris but without prior myocardial infarction (42 "in crescendo" angina and 58 recent onset angina). Also in these patients were found the same results; with the exception of ejection fraction which was more slight in patients with "in crescendo" angina (p less than 0.01). These data confirm that patients with unstable angina are an heterogeneous group in which comparison is unreliable and that the severity of clinical symptoms is not related to the degree of angiographic coronary lesions.

[Transesophageal echocardiography and risk factors for embolism]. / Ecocardiografia transesofagea e indicatori di rischio embolico.

Echocardiography is the main diagnostic tool for thromboembolic risk evaluation in patients with atrial fibrillation (AF). Transthoracic echocardiography (TTE) has low sensitivity and specificity in thrombus detection, especially in left atrium appendage; on the other hand the transesophageal approach (TEE) provides information about thrombi located anywhere. In recent years, large trials on thromboembolic risk in AF have given strong value to echocardiographic risk factors such as left atrial enlargement and left ventricular dysfunction, well detected by TTE. Transesophaged echocardiography can be considered the best technique to study factors even more closely correlated to thromboembolic risk, such as spontaneous echocontrast or left atrium appendage abnormalities both anatomical (enlargement and malformations) or functional (low peak velocity). Preliminary data from new trials, like SPAF III and FASTER, confirm this fact. On the other hand, TEE permits the study of thoracic aorta and atheromasic lesions, which can be considered additional direct (ulcerated plaques) or generic thrombotic risks.

[Cost of diagnostic and therapeutic hemodynamic procedures: comparison with DRG reimbursement]. / Costo delle procedure emodinamiche diagnostiche e terapeutiche: confronto con il rimborso secondo DRG.

BACKGROUND: The cumulative costs of diagnostic and interventional procedures in the catheterization laboratory in public hospitals are still largely unknown, notwithstanding the present stress upon the cost-effectiveness issues in medicine. METHODS: From January through April 2000 we have evaluated procedures in the catheterization laboratory of the Ravenna USL. Costs taken into consideration were the following: the mean cost of materials for each type of examination and of medications used for each patient, personnel costs, machinery mortgages' costs, ambulance transportation's costs, and general hospital expenditures. DRGs and reimbursements have been calculated on the basis of clinical indications and modalities of procedures. RESULTS: During the evaluation period 268 patients have been studied. The procedures taken into consideration included: 135 coronary angiographies, 36 right and left catheterizations plus coronary angiography, 87 coronary angiographies plus percutaneous coronary intervention (PCI), 10 PCI. The total cost of diagnostic catheterization was Itl 1,226,000 (Euro 632) whereas that of each PCI (including stent implantation in 80% of cases) associated in 87 cases with coronary angiography was Itl 5,956,000 (Euro 3044). Patients with an acute coronary syndrome or heart failure were mostly studied during their first hospital stay; those with stable disease (stable angina, previous myocardial infarction, valvular heart disease or cardiomyopathy without heart failure) were studied during ordinary hospital admission or in the context of a day-hospital. DRGs and corresponding reimbursements for the different clinical situations were the following: unstable angina DRG 124 valued at Itl 6,180,000; stable angina DRG 125 valued at Itl 3,900,000; acute or recent myocardial infarction with or without complications DRG 121 or 122 valued at ItI 8,290,000 or Itl 5,900,000; heart failure in valvular heart disease or cardiomyopathy DRG 124 valued at Itl 6,180,000; valvular heart disease or cardiomyopathy DRG 125 valued at Itl 3,900,000. The DRG for a PCI is no. 112 valued at Itl 10,235,000. CONCLUSIONS: The costs of diagnostic and interventional hemodynamic procedures were acceptable and proportional to the DRG-related reimbursements. Appropriately indicated procedures and their quick execution during the first hospital stay lead to global economic savings for the health care system and are also clinically advantageous for the individual patient.

[The correlation between the type of positivity of the tilt test and a simultaneous electroencephalogram: the preliminary results]. / Correlazione tra tipo di positività del tilt test ed elettroencefalogramma simultaneo: risultati preliminari.

BACKGROUND: Today the first-choice examination to study neurally-mediated syncope is the tilt test. There are still many aspects to be clarified on the pathophysiology of neurally-mediated syncope, and much uncertainty remains on the therapeutic procedure to adopt. Recent research has investigated the role of neurohumoral agents, thus shifting interest to the pathogenetic role of the central nervous system, over and above that of the already widely studied vegetative nervous system. This is why we decided to carry out the tilt test with simultaneous electroencephalogram (EEG) recordings, with the aim of documenting any possible correlation between test positivity, according to Sutton's classification, and the EEG results. METHODS: We studied 15 patients (8 males, 7 females, age range 18-74 years) with a history of repeated syncopal and presyncopal episodes who had formerly undergone numerous clinical and instrumental examinations, including EEG, with negative results. The tilt test was carried out with continuous measurement of blood pressure (Ohmeda Finapres System) and simultaneous EEG recording. RESULTS: Ten patients (66%) were positive, 6 had experienced syncope episodes (4 type 2A and 2 type 1) and 4 presyncope (1 type 2A and 3 type 1). In all the syncope positive patients the EEG showed modifications in comparison with basal EEG, whereas only 50% of the presyncope positive patients showed slight alterations. There was no EEG alteration for tilt negative patients. The EEG result was markedly different in patients with tilt-induced type 2A syncope in comparison with those with type 1. Type 2A showed the following: 1) slowdown and reduced amplitude of electrical activity during the prodromes; 2) during the syncope, first pseudorhythmic then polymorphic delta activity were followed by total disappearance of activity ("flat" EEG); 3) then, in inverse sequence, reappearance of polymorphic then pseudorhythmic delta activity (average duration of syncope 37 s); 4) lastly, slowdown and reduced amplitude of electrical activity similar to that preceding the syncope. Whereas type 1 revealed: 1) no alteration of electrical activity during the prodromes; 2) during the syncope, first theta then polymorphic delta activity (average duration of syncope 16 s); 3) subsequent normal EEG. CONCLUSIONS: These observations indicate a correlation between the type of tilt test positivity and the EEG results, the latter being markedly more serious in type 2A than in type 1. EEG behavior, different in the two types also during the prodromes and the post-syncopal phase, would suggest a cerebral circle vasoconstriction mechanism in type 2A but not in type 1 mixed with a prevalent vasodepressive component. Should these preliminary results be confirmed by further data there will be evident clinical, prognostic and therapeutic implications. In the light of the considerably different involvement of the central nervous system, we believe it will be necessary to redefine the various types of neurally-mediated syncope in terms of seriousness. Simultaneous EEG could be proposed routinely in tilt test execution and become a determining factor in the choice of a therapeutic option.

Bosentan fosters microvascular de-remodelling in systemic sclerosis.

Bosentan, a dual endothelin receptor antagonist, may reduce blood pressure by blocking the vasoconstrictor effect of endothelin-1. In systemic sclerosis (SSc) nailfold videocapillaroscopy (NVC); allows diagnostic and follow-up of microvascular damage. Distinct NVC patterns have been identified for the evaluation of severity of SSc microvascular damage. The objective of this study is to evaluate the modification of the microvasculature under Bosentan therapy in SSc patients with pulmonary arterial hypertension (PAH). Nine patients with PAH related to SSc in New York Heart Association classes III-IV were treated with Bosentan 125 mg twice a day. NVC optical probe videocapillaroscopy equipped with 100× and 200× contact lenses and connected to image analyse software was performed before and after 12 months of Bosentan therapy to evaluate the modification of microvasculature. Nine PAH SSc patients treated with Iloprost were used as controls. Before Bosentan therapy, seven patients showed at NVC severe loss of capillaries with large avascular areas and vascular architectural disorganisation which are typically "late" SSc pattern. After 12 months of Bosentan, NVC pattern changed in seven patients from "late" into "active" SSc pattern. The disappearance of avascular areas and capillary haemorrhages was the most striking result. Two patients had an "active" SSc pattern, not modified by Bosentan treatment. These data show that Bosentan may improve NVC pattern in SSC and the presence of new capillaries suggests that it may favour angiogenesis. Bosentan may improve and stabilise the microvasculature in long-term treatment modulating the structural modifications detected by NVC.