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.

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.

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.

[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.

One-year outcome in multivessel coronary disease patients undergoing coronary stenting.

The purpose of this study was to assess 1-year clinical outcome of patients with multivessel coronary artery disease (CAD) who underwent coronary stenting and were prospectively enrolled in the Registro Impianto Stent Endocoronarico (RISE). Of 939 consecutive patients included in the registry, 377 patients with angiographic evidence of multivessel CAD had a 1-year clinical follow-up. All patients underwent PTCA and single or multiple stenting in at least one vessel. Angiographic optimization was usually performed by using high-pressure balloon dilation. After the procedure, continuation of aspirin (at least 250 mg/day) was recommended, whereas the use of anticoagulation or ticlopidine was determined by the physician in charge of the patient in the various centers. Major adverse cardiac events were defined as death, Q-wave or non-Q-wave myocardial infarction and target vessel revascularization. Mean age of patients (311 men, 66 women) was 60 +/- 10 years. Globally, there were 596 stents implanted (72% Palmaz-Schatz stents) in 434 vessels. In about 75% of the procedures, an inflation pressure > 12 atm was used. Angiographic success rate was 98.5%. After stenting, 77% of patients received antiplatelet treatment with ticlopidine and aspirin. During hospitalization, there were 34 major adverse cardiac events in 24 patients. At 1-year follow-up, 309 patients were alive and event-free; cumulative incidence of death, myocardial infarction, and repeat revascularization were 2.9%, 4.7%, and 10.8%, respectively. By Cox regression analysis, multiple stents implantation (HR 1.72, 95% CI 1-2.97), left anterior descending artery revascularization (HR 1.86, 95% CI 1.01-3.42), use of inflation pressure > 12 atm (HR 0.93, 95% CI 0.89-0.97), ticlopidine therapy (HR 0.41, 95% CI 0.23-0.74), and stent length (HR 1.03, 95% CI 1.01-1.05) were associated with 1-year major cardiac events. In patients with multivessel CAD undergoing stent implantation in at least one vessel, 1-year follow-up is favorable and the need for repeat revascularization procedures, based on clinical data, is lower than previously reported for conventional PTCA. Cathet. Cardiovasc. Intervent. 48:343-349, 1999.

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.

Predictors of major in-hospital ischemic complications and length of hospital stay after coronary stenting.

Although recent data show that coronary stenting reduces procedural complications and late restenosis, major concern has been expressed about the greater hospital cost associated with the use of this device as compared to conventional coronary angioplasty. Since length of hospital stay after surgical procedures is a major determinant of resource use, the identification of variables associated with an excessively long hospital stay after intracoronary stent placement may have important practical consequences. The purpose of this study was to assess factors responsible for the occurrence of in-hospital complications and prolonged hospital stay after coronary stenting in 939 consecutive patients enrolled in the Registro Impianto Stent Endocoronarico (RISE Study Group). Consecutive patients undergoing coronary stent implantation at 16 medical centers in Italy were prospectively enrolled in the Registry. Clinical data, qualitative and quantitative angiographic findings were obtained from data collected in case report forms at each investigator site. Major ischemic complications were considered death, Q-wave myocardial infarction, emergency bypass surgery and emergency repeat angioplasty. The study group consisted of 939 patients (781 men, 158 women with a mean age of 59 years) in whom 1392 stents were implanted in 1006 lesions and expanded at a maximal inflation pressure of 14.7 +/- 3 atmospheres. The great majority of patients (92%) received only antiplatelet drugs after coronary stenting. During hospitalization, there were 45 major ischemic complications in 39 patients (4.2%): 13 events were related to acute or subacute thrombosis (1.4%). On multivariate logistic regression analysis, the following factors were predictive of in-hospital complications: increasing age (OR 2.19, 95% CI 1.18-4.07), unplanned stenting (OR 3.46, 95% CI 1.65-7.23) and maximal inflation pressure (OR 0.83, 95% CI 0.75-0.93). Mean hospital stay after stent implantation was 4.1 +/- 4.4 days and was related, by multivariate regression analysis, to female sex (p = 0.0001), prior bypass surgery (p = 0.03), non-elective stenting (p = 0.0001), use of anticoagulation (p = 0.0001) and development of major ischemic complications (p = 0.0001). This Registry shows that in an unselected population of patients undergoing coronary stenting, major ischemic complications occur at a relatively low rate (4.2%) and thrombotic events can be kept at 1.4%, despite the omission of anticoagulation in the great majority of patients. Length of hospital stay was affected by the occurrence of major ischemic complications, unplanned stenting, use of anticoagulation, female sex and prior bypass surgery. Accumulating experience, further reduction in complications and complete omission of anticoagulation may decrease length of hospital stay, thus reducing the use of resources after coronary stenting.

Coronary restenosis after optimal (stent-like) initial angiographic results obtained by traditional balloon angioplasty.

BACKGROUND AND OBJECTIVE: Elective native coronary artery stenting has shown its efficacy in lowering restenosis rates (RR) usually occurring after balloon angioplasty (PTCA). However ability of conventional PTCA to consistently provide low RR, through the achievement of large acute stent-like angiographic results, has not been investigated. This study was conducted to: (1) assess ability of optimal initial dilatation (OID), defined by residual lumen narrowing < or = 20%, significantly reduce current high RR following traditional PTCA; (2) evaluate the efficacy of OID obtainable by conventional PTCA in influencing adverse effects of single variables predisposing to restenosis. METHODS: Of consecutive 601 patients who underwent PTCA, 569 (94.6%), 483 men and 86 women, aged 38-76 years, had a successful procedure on 645/678 lesions (95.1%). After a plaque fracture was obtained by the first inflation, step-increases in pressure of 1 atm and 60 second-inflation-times were applied, until a large lumen (the nearest to normal) and smooth contours were seen, or any wall damage detected by using step-by-step angiographic tests. Acute optimal results (group A) were 450 (69.7%) and sub-optimal results (group B) were 203 (30.3%). After a mean time of 9 +/- 1.8 months, 543 patients (95.4%) had angiographic restudy on 611 (94.7%) successfully treated lesions. RESULTS: Restenosis (> 50% stenosis at restudy) occurred in 27.1% of patients and in 24.5% of lesions. RR was 18.8% in group A and 37.8% in group B (p < 0.0001). Significant lower RR were observed in group A in comparison with group B, for single variables examined, except for length > 10 mm. By multivariate analysis of all treated lesions, sub-optimal initial dilatation, unstable angina, lesion length > 10 mm and eccentricity emerged as major determinants of restenosis. Following OID only length > 10 mm was highly predictive of this event and, in the absence of this adverse variable, RR was only 13.6%. CONCLUSION: Counterbalancing adverse effects of many variables predisposing to restenosis, OID obtained by traditional PTCA seem to significantly reduce the risk of recurrence, particularly in lesions no longer than 10 mm.

Steroid-eluting electrodes prevent chronic pacing threshold rise in the atrial chamber after oral propafenone administration.

The aim of the study was to evaluate chronic atrial pacing threshold increase after oral propafenone therapy. Fifty patients affected by advanced AV block and sick sinus syndrome were studied at least 6 months after pacemaker implantation, before and after oral propafenone therapy (450-900 mg/day based on body weight). The patients were subdivided into three groups as to the type of electrode implanted, all three unipolar: group I (20 patients) Medtronic CapSure 4003, group II (13 patients) Medtronic Target Tip 4011, group III (17 patients) Medtronic 4057 screw-in leads. In all cases, Medtronic unipolar pacemakers were implanted with the same noninvasive autothreshold measurement method. Propafenone and 5-OH-propafenone blood levels were measured 3-5 hours after drug administration. The packing autothreshold was measured at 0.8, 1.6, and 2.5 V by reducing the pulse width. After propafenone, groups II and III showed a statistically significant threshold rise (P ranging from < 0.01 to 0.05), whereas no significant difference was found in group I. Propafenone and 5-OH-propafenone blood vessels did not show any significant difference among the three groups. Strength-duration curves were drawn for the three groups before and after propafenone: at baseline the curves shifted to the left with the steep part above the knee, clearly favoring CapSure over the other two groups. After propafenone, the curves shifted to the right, with the flat par progressively more evident in groups II and III. In the atrial chamber, steroid-eluting leads prevented threshold increase after propafenone therapy, in contrast with a significant threshold rise with conventional porous and screw-in leads.

[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.

[Presence of patent foramen ovale in different heart diseases: incidence in 211 consecutive patients studied by transesophageal echocardiography]. / Presenza di forame ovale pervio in diverse cardiopatie: incidenza in 211 pazienti consecutivi studiati con eco transesofageo.

BACKGROUND: Contrast echocardiography during the decompression phase of the Valsalva manoeuvre in course of transesophageal echo study is the ideal method to identify patent foramen ovale. METHODS: In order to evaluate the incidence of patent foramen ovale in patients with different cardiac diseases we performed contrast injection in 211 consecutive pts submitted to TEE (Transesophageal Echocardiography) in our laboratory between march 1991 and march 1993. RESULTS: Fiftythree of 211 pts (25%) presented a patent foramen ovale. The incidence in the different cardiac diseases was as follows: 0% in rheumatic mitral disease, 23% in aortic valve disease, 17% in mitral and/or aortic valve prosthesis, 29% in congenital heart disease other than interatrial septal defect, 44% in mitral valve prolapse and 92% in atrial septal aneurysm. CONCLUSIONS: This study indicates that patent foramen ovale is a common finding in different cardiac pathologies and frequent in mitral valve prolapse and even more in atrial septal aneurysm. In case of peripheral embolism of likely cardiac origin, the patency of the foramen ovale must be recognized, especially when these two latter cardiac anomalies are identified.

Trapidil (triazolopyrimidine), a platelet-derived growth factor antagonist, reduces restenosis after percutaneous transluminal coronary angioplasty. Results of the randomized, double-blind STARC study. Studio Trapidil versus Aspirin nella Restenosi Coronarica.

BACKGROUND: Trapidil is an antiplatelet drug with specific platelet-derived growth factor antagonism and antiproliferative effects in the rat and rabbit models after balloon angioplasty. METHODS AND RESULTS: The Studio Trapidil versus Aspirin nella Restenosi Coronarica (STARC) is a multicentric, randomized, double-blind trial to assess the effects of trapidil in angiographic restenosis prevention after percutaneous transluminal coronary angioplasty (PTCA). Patients received either trapidil 100 mg TID or aspirin at the same dosage at least 3 days before angioplasty and for 6 months thereafter. Coronary angiograms before PTCA, after PTCA, and at 6-month follow-up were quantitatively analyzed with manual calipers. Of the initial 384 patients recruited, 254 were evaluable for restenosis analysis (128 trapidil, 126 aspirin). Restenosis, defined as a loss of initial percent gain after PTCA of at least 50% (primary end point), occurred in 24.2% of the trapidil group and 39.7% of the aspirin group (P < .01). A similar result was obtained when restenosis per vessel was considered (trapidil, 23.3%; aspirin, 36.9%; P = .018). Clinical events at follow-up were similar in the two groups except that recurrent angina was significantly more frequent in the aspirin group, 43.7% versus 25.8% in the trapidil group (P < .01). Trapidil was well tolerated: only 6 patients had to discontinue the drug because of side effects, which was not different from the aspirin group. CONCLUSIONS: Trapidil reduces restenosis after PTCA at the dosage of 100 mg TID and favorably influences the clinical outcome thereafter.

The trapidil restenosis trial (STARC study): background, methods and clinical characteristics of the patient population.

Restenosis remains the principal drawback of percutaneous transluminal coronary angioplasty (PTCA) since 30-35% of patients still experience it 6 months after the intervention. Several studies have clearly demonstrated that restenosis is a complex multifactorial process that involves smooth muscle cell (SMC) migration and proliferation in the intimal layer of the coronary artery. Among others, the platelet-derived growth factor (PDGF) seems to play an important role in this process. That is why researches have been made in finding and developing new agents able to inhibit PDGF. Trapidil (triazolopyrimidine) (T), is a potent PDGF inhibitor that has been efficacious in preventing restenosis after balloon angioplasty in the experimental animal and after PTCA in a limited clinical trial. The Trapidil Restenosis Trial (STARC study) is a double blind randomized trial of T 100 mg t.i.d. vs. Aspirin (ASA) 100 mg t.i.d. 360 patients have been enrolled from April 1990 until May 1992, excluding recent myocardial infarctions, thrombolysis, restenotic and venous graft lesions and 302 have terminated follow-up. This paper describes the clinical background, the protocol and baseline data of the patient population including data regarding initial stenosis and type of vessel treated.

[The prevention of nitrate tolerance in angina patients treated with transdermal nitroglycerin: a comparison of 2 therapeutic regimens (therapeutic outlook versus dosage reduction)]. / Prevenzione della tolerance ai nitrati in pazienti anginosi trattati con nitroglicerina per via transdermica: confronto di due schemi terapeutici (finestra terapeutica verso riduzione di dosaggio).

We studied the long-term antianginal and anti-ischemic effects of two dosage regimens designed to prevent tolerance to transdermal nitroglycerin (TNTG): (1) 10 mg TNTG applied for 16 h with a 'nitrate-free' interval of 8 h; (2) 10 mg TNTG applied for 16 h followed by a 'nitrate-low' interval of 5 mg applied for 8 h. 129 patients completing a 3-month study period were evaluated by repeated exercise tests. Both regimens significantly increased maximum exercise duration at 3 months, from 699.1 +/- 23.4 to 833 +/- 21.9 s and from 686.1 +/- 20 to 789.6 +/- 22.6 s, respectively, reduced the number of patients with 1 mm S-T segment depression and increased the time duration to 1 mm S-T segment depression. Marked reductions in anginal attacks was observed in both groups: from 6.5 to 0.15 attacks per week and from 6.0 to 0.15 attacks per week, respectively. No statistically significant differences were found between the groups, and both regimens were well tolerated. In conclusion, our results demonstrate sustained antianginal efficacy, without tolerance, of either 'nitrate-free' of 'nitrate-low' interval therapy with transdermal nitroglycerin.

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.