[Application of enoxaparin simultaneously with fibrinolysis in patients with acute myocardial infarction with ST-elevation].

INTRODUCTION: Applied simultaneously with fibrinolytic therapy, low-molecular heparin enoxaparin is showing the potential of improving efficacy with rare adverse effects. Our objective was to investigate if enoxaparin with streptokinase (SK) in patients with acute myocardial infarction (AMI) had better effect than unfractioned heparin (UFH). MATERIAL AND METHODS: The patients with AMI with ST elevation where SK was applied, were divided into two groups: 1. In the study group (N=32, SK+E) both SK and enoxaparin were administered (E, 30 mg intravenously before SK, then after SK 80 mg subcutaneously every 12 hours for 3 days); 2. The patients of the control group were given continuous infusion of UFH 4 hours after SK (1000 i.j. per hour, 3 days). Two groups were similar regarding average age, previous coronary events and diabetes mellitus. RESULTS: The reperfusion, depending mostly on fibrinolytic therapy, was successful in both groups (71.9% vs. 65.8%). The recurrent ischemia was less frequent in the group where enoxaparin was used (18.8% vs. 40.6%, p=0.055), as well as heart failure (15.6% vs. 53.2%, p=0,095). There was no difference in adverse effects. CONCLUSIONS: Enoxaparin used simultaneously with streptokinase in patients with AMI with ST elevation was safe and effective. The recurrent ischemia, the parameter of "infarcted" coronary artery reoclusion, is less frequent in patients who had enoxaparin than unfractioned heparin with fibrinolytic therapy.

Haemodynamic and clinical effects of ularitide in decompensated heart failure.

AIMS: Ularitide is a synthetic form of urodilatin, a natriuretic peptide produced in the kidney with vasodilating, natriuretic, and diuretic effects, that offers promise for the management of decompensated heart failure (DHF). We assessed the efficacy and safety of ularitide in treating patients with DHF. METHODS AND RESULTS: In this Phase II randomized, double-blind, placebo-controlled trial, 221 DHF patients received either placebo (n=53) or ularitide at 7.5 ng/kg/min (n=60), 15 ng/kg/min (n=53), or 30 ng/kg/min (n=55) as a 24-h continuous infusion. At 6 h, ularitide demonstrated a significant decrease in pulmonary capillary wedge pressure (P=0.052, P=0.000004, P=0.000002, respectively) and improved dyspnoea score in the 7.5, 15, and 30 ng/kg/min ularitide group (P=0.0026, P=0.0026, P=0.0013, respectively). Ularitide reduced systemic vascular resistance and increased cardiac index for the 15 and 30 ng/kg/min groups (P=0.017, P=0.00002, respectively). Systolic blood pressure (BP) decreased dose dependency. Heart rate and serum creatinine were unchanged through day 3. Most frequently reported drug-related adverse events through day 3 in all ularitide groups were dose-dependent BP decrease and hypotension. CONCLUSION: Ularitide lowered cardiac filling pressures and improved dyspnoea without apparent early deleterious effects on renal function in DHF patients. These results suggest that ularitide may play a role in the management of DHF.

Effects of atropine and pirenzepine on heart rate turbulence.

BACKGROUND: It has been shown that mortality risk in patients after myocardial infarction could be estimated by heart rate turbulence (HRT), a short-term change in heart rate after ventricular premature beat (VPB), presumably caused by baroreceptor mechanism. We sought to determine whether pharmacological blockade with atropine, or augmentation of vagal tone with pirenzepine given in small doses would influence HRT. METHODS: In 30 patients with normal echocardiogram, and without signs or symptoms of coronary artery disease, after electrophysiologic examination or radiofrequency ablation for supraventricular arrhythmias was completed, turbulence onset (TO) and turbulence slope (TS) in basal state, after 1.3 mg IV pirenzepine and finally, after atropine in dose of 0.04 mg/kg of body weight were compared. RESULTS: As assessed by Friedman ANOVA test both pirenzepine and atropine caused a significant change in both TO (P < 0.01) and TS (P < 0.01). The mean basal TO of -3.6 +/- 2.9%, changed after pirenzepine to -5.99 +/- 5.6% (P < 0.01), and after atropine it changed to -3.3 +/- 18.1% (P < 0.01). The mean basal TS of 18.6 +/- 10.1 ms/R-R interval increased after pirenzepine to 26.8 +/- 19.9 ms/R-R interval (P < 0.05), and decreased after atropine to 1.2 +/- 0.8 ms/R-R interval (P < 0.01). Mean cycle length increased after pirenzepine from 706.8 +/- 106.8 to 830 +/- 151.9 ms (P < 0.01), and decreased after atropine to 454.2 +/- 58.1 ms (P < 0.01). CONCLUSION: A conclusion could be drawn that vagomymetic manipulation with intravenous pirenzepine increases HRT; vagal blockade with atropine decreases HRT. This finding suggests that a normal vagal innervation of heart is a prerequisite for the phenomenon of HRT.

[Outcome and prognosis of surgical treatment in patients with severe aortic stenosis with respect to the duration and severity of associated aortic regurgitation]. / Ishod i prognoza hirurskog lecenja bolesnika sa teskom aortnom stenozom u odnosu na postojanje i tezinu pridruzene aortne regurgitacije.

INTRODUCTION: It is not clear whether associated aortic regurgitation (AR) should be regarded as a risk factor in patients undergoing surgery for severe aortic stenosis (AS). Some authors have suggested that morbidity and mortality are increased in these patients as compared to patients operated for pure AS, whereas others have found no difference of the outcome and prognosis between these groups. OBJECTIVE: This study made an attempt to compare the outcome and prognosis following the surgical intervention in patients with severe AS and associated AR and those operated for pure AS, as well as to determine predictive value of clinical, functional and echocardiographic data for the outcome of surgery. METHODS: Study population consisted of 122 consecutive patients operated at Dedinje Cardiovascular Institute during 1999 due to severe AS, defined as mean gradient over aortic valve >30 mmHg. The patients were divided into AS group (63 patients with AS without AR or with mild AR) and AS+AR group (59 patients with AS and moderate, severe or very severe AR). The patients were subjected to control clinical, functional and echocardiographic examinations 12 and 18 months following the surgery. RESULTS AND DISCUSSION: Preoperatively, the patients in AS group were older and had coronary artery disease more frequently, whereas patients in AS+AR group had higher left ventricular volumes and mass. Preoperative NYHA class, ejection fraction, mean gradient over aortic valve, type and size of the implanted mechanical prosthesis, and the incidence of associated coronary artery bypass surgery were similar between the groups. Similarly, the operative mortality was similar in AS and AS+AR groups (1.6% vs 8.5%, respectively, p=0.11). Twelve months postoperatively, there were no difference of average NYHA class and NYHA class III/IV between the groups. The patients in AS+AR group were unable to walk >300 meters on 6 minute walk test more frequently than those in AS group (64% vs. 36%, respectively; p=0.043). Eighteen months postoperatively, NYHA class III/IV was found more frequently in AS+AR than in AS group (26% vs. 8%, respectively; p=0.0343). In patients with associated AR, there was no difference of NYHA class with respect to the severity of AR (p=0.815). Multivariate analysis found the association of more than mild AR as an independent predictor of poor functional capacity, irrespective of its severity. CONCLUSION: Patients with severe AS and associated AR have poorer postoperative functional capacity as compared to patients operated for pure AS.

Effect of single doses of SLV306, an inhibitor of both neutral endopeptidase and endothelin-converting enzyme, on pulmonary pressures in congestive heart failure.

SLV306, a potent neutral endopeptidase (NEP) inhibitor with additional endothelin-converting enzyme (ECE)-inhibitory activity, in doses of 200, 400, and 800 mg reduced pulmonary and right atrial pressures, although there was not a clear dose response. Systemic blood pressure, heart rate, and cardiac output were unaffected. SLV306 increased plasma natriuretic peptides and big endothelin-1 levels in a dose-dependent manner, confirming NEP and ECE inhibition. The combined inhibition of NEP and ECE may be useful in heart failure by reducing right and left cardiac filling pressures.

[Endovascular procedures in the treatment of obstructive lesions of the brachiocephalic arteries]. / Endovaskularne procedure u tretmanu opstruktivnih promena brahiocefalnih arterija.

BACKGROUND: To assess the early effects, possible risks, and long term results of percutaneous transluminal angioplasty (PTA) of brachiocephalic trunk (BT) and subclavian arteries (SA). METHODS: During the period of 11 years, in 92 patients (57 males--62%, mean age 53.5 +/- 7.8 years) 93 PTA of SA/BT were performed; 70 (75%) lesions were stenosis, while 23 (25%) lesions were occlusions with mean diameter stenosis percent of 83.1 +/- 6.2%. Clinical indications were: vertebrobasilar insufficiency (n = 57), upper limb ischemia (n = 40), coronary steal syndrome (n = 4) and scheduled aorto-coronary bypass, using internal thoracic artery (ITA) (n = 4 asymptomatic patients). Mean lesion length was 22 +/- 8 mm. RESULTS: Eighty one (87%) out of 93 lesions were successfully dilated; all of 12 (13%) failures were due to unsuccessful recanalisation of occluded arteries. In 10 patients 10 stents were implanted (2 in BT and 8 in left SA). There were 6 (6.5%) procedural complications: 1 dissection, 1 thrombosis of the left SA, transient ischemic attack in 2 patients, and 2 cases of dislocation of atheromatous plaque from the right SA into the right common carotid artery. During the follow-up of 48 +/- 3 months, 16(20%) restenoses were treated by PTA (n = 7) or operatively (n = 9). Primary and secondary patency for all lesions treated during 11 years was 87% and 80%, respectively (stenosis: 97% and 89%; occlusions: 58% and 58%). CONCLUSION: PTA with or without stenting was relatively simple, efficient and safe procedure. It required short hospitalization with low treatment costs. If any of suboptimal results or chronic occlusions were present, the implantation of endovascular stents should have been considered.