Francesco Giambanco

Comparison of Ivabradine Versus Metoprolol in Early Phases of Reperfused Anterior Myocardial Infarction With Impaired Left Ventricular Function: Preliminary Findings

BACKGROUNDnbeta-blockers in ST-segment elevation myocardial infarction (STEMI) are indicated for patients without a contraindication, particularly in patients with high heart rates (HR) or blood pressures. Epidemiological studies have shown that elevated HR represents a risk factor for cardiovascular morbidity. The study investigates the feasibility, tolerability, and the effects after 30 days of follow-up of ivabradine (IVA) versus metoprolol (METO) in early phases of anterior STEMI reperfused by percutaneous coronary intervention (PCI).nnnMETHODS AND RESULTSnPatients with a first anterior STEMI, Killip class I-II, an acceptable echocardiographic window, and admitted within 4hours of the onset of symptoms, with an ejection fraction <50%. METO or IVA, 12hours after PCI (double blind), were administered twice per day. Blood pressure (BP), heart rate (HR), electrocardiogram (ECG), and laboratory parameters were monitored during the study. At entry, day 10, day 30, and day 60, by echocardiography, the ESV, EDV, E/A ratio, E wave deceleration time, isovolumetric relaxation time were measured. A total of 155 (50 females, 105 males) patients were randomized in 2 groups: a group received METO (76 patients) 12hours after PCI and a group received IVA (79 patients) 12hours after PCI. The 2 groups were similar for clinical characteristics. No difference was evidenced in HR, systolic blood pressure, diastolic blood pressure, age (range, 39-73 years), sex, ejection fraction (EF), creatine kinase peak, between the 2 groups at entry. Both groups were similar for time to angiography and interventional procedures and number of vessels diseased. IVA group: the 79 patients showed 2 side effects and 5 readmissions: 4 for ischemic events and 1 for heart failure, and 1 sudden death; METO group: the 76 patients had 4 ischemic events, 2 side effects, and 1 patient died during re-acute MI (intrastent thrombosis) and 8 readmissions for heart failure signs. The systolic blood pressure and diastolic blood pressure showed a significant reduction in both groups, P < .0001, respectively), and significant lower values were observed in METO group, P=.0001). The HR was significantly reduced in both groups, P < .0001). IVA group showed a significant increase in EF, P=.0001, with concomitant reduction in ESV and EDV (P=.0001, and .048, respectively). The diastolic parameters were similar in both groups during study period.nnnCONCLUSIONSnOur results suggest that ivabradine may be administered early (12hours after PCI) to patients with successful PCI for anterior STEMI with an impaired left ventricular function and high HR and sinus rhythm. A larger sample of patients and further studies are required to evaluate the effects of ivabradine on clinical end points.

Is delayed facilitated percutaneous coronary intervention better than immediate in reperfused myocardial infarction? Six months follow up findings

AbstractBackground: There are several new strategies proposed to improve the outcome of patients with ST-elevation myocardial infarction (STEMI). One approach is the resurgent use of facilitated percutaneous coronary interventions (PCI). Until recently, deciding whether immediate PCI after combined treatment (facilitated PCI) is more appropriate than delayed PCI (short time) has not been investigated. The aim of this study, therefore, was to investigate the outcomes in patients initially successfully treated pharmacologically and immediate PCI < 2 hr, and in patients initially successfully treated with pharmacological therapy and with delayed PCI (12–72 h).n Methods: 451 reperfused STEMI patients, aged 18 to 75 years, class I–II Killip, with an acceptable echocardiographic window and admitted within 12 hs of the onset of symptoms were randomized into two groups. All patients had to have successful reperfusion, to receive the combination of a standard tirofiban infusion or abciximab plus half dose rtPA. Thereafter, patients were sub-grouped as follows:group 1 (immediate PCI) patients had PCI within 2 h; and group 2 (delayed PCI) patients in which PCI was performed after 12 hs and within 72 hs.n Results: The 225 reperfused (immediate-PCI) and 226 reperfused (delayed-PCI) patients (time from randomization to PCI 165 ± 37 min in immediate PCI versus 45.1 ± 20.2 h in delayed PCI group) showed similar results in ejection fraction, CK release and patency of the IRA. In addition, the delayed PCI group showed a significant reduction in ischemic events, restenosis and bleedings (P = 0.005, 0.01, 0.01 respectively) and significant reduced angiographic evidence of thrombus formation in the infarction-related artery (IRA) (p = 0.001).n Conclusion: Our data suggest the safety and possible use of delayed facilitated PCI in patients with STEMI, and that delayed PCI in patients treated with combined lytic and IIb/IIIa inhibitors appears to be as effective and possibly superior (reduced ischemic events and repeat PCI) as immediate PCI. The patients in this study were successfully reperfused, with TIMI-3 flow and our data may not apply to patients with TIMI 0–2 flow. This strategy could allow transferring the reperfused patients and performing PCI after hours < 72 hours and not immediately, thereby reducing the number of urgent PCI and costs, obtaining similar results, but mostly causing less discomfort to the patient. Our results had to be interpreted with caution, because current guidelines do not recommend the combined therapy, but suggest further studies.Abbreviated abstractThe study was aimed to investigate the outcomes in patients initially successfully treated pharmacologically and immediate PCI < 2 h, and in patients initially successfully treated with pharmacological therapy and delayed PCI (12–72 h). All patients had to have successful reperfusion, to receive the combination of a standard abciximab or tirofiban infusion plus half dose rtPA. Similar results were observed in both groups. Delayed PCI group showed a significant lower incidence in restenosis (0.01), minor bleedings (0.005), ischemic events (0.01) and a reduced angiographic evidence of thrombus formation in IRA (0.001). Our data suggest the safety and possible use of delayed facilitated PCI in patients with STEMI. Our results had to be interpreted with caution, because current guidelines do not recommend the combined therapy, but suggest further studies.

Combination of indomethacin and statin compared with indomethacin and placebo in patients with a first episode of acute pericarditis: preliminary findings.

The aim of the present study was to evaluate the safety and efficacy of the combination of indomethacin and statin compared with indomethacin plus placebo in patients with a first episode of pericarditis. A total of 55 consecutive patients with acute pericarditis were randomized in a double-blind manner into two groups: group 1 (statin group) was treated with 150 mg of indomethacin plus 10 mg of rosuvastatin, and group 2 (placebo group) was treated with 150 mg of indomethacin plus placebo. Both groups received treatment up to the normalization of inflammation markers and for the following week. Clinical and laboratory assessments [white cell count, ESR (erythrocyte sedimentation rate) and CRP (C-reactive protein), troponin I, creatine kinase and brain natriuretic peptide plasma levels], ECG and echocardiogram were performed at baseline and daily up to discharge. All of the patients were followed as outpatients for 3 months to evaluate any recurrence of pericarditis. The two groups were similar in age, sex and laboratory parameters [group 1 (the statin group), n=28 patients; gender, 18 male and ten female; and age, 29.5+/-5.7 years; group 2 (placebo group), n=27 patients; gender, 16 male/11 female; and age, 29.2+/-4.8 years]. The statin group, when compared with the placebo group, had a significantly faster reduction in CRP values (5.0+/-1.0 compared with 6.0+/-2.0 days respectively; P=0.022), ST segment normalization (3.5+/-1.0 compared with 4.5+/-1.0 days respectively; P=0.001), pericardial effusion (4.5+/-1.0 compared with 5.5+/-1.0 days respectively; P=0.001) and ESR (5.0+/-1 compared with 6.0+/-2 days respectively; P=0.022). Our results show that the combination of statin and indomethacin treatment in patients with acute pericarditis is feasible, with a significant reduction in inflammatory markers and a favourable trend in hospitalization time (5.5+/-2.0 compared with 6.5+/-2.0 days respectively; P=0.069). However, these preliminary findings require further studies in a larger sample of patients.

Effects of Administration of Glycoprotein IIb/IIIa Receptor Antagonists in Patients with Failed Thrombolysis

AimTo evaluate the effectiveness of glycoprotein (GP) IIb/IIIa receptor antagonists in patients with acute myocardial infarction (AMI) who have undergone unsuccessful thrombolysis.DesignRandomised, prospective, single-blind trial.Patients and Participants84 patients (62 males, 22 females, aged 40 to 80 years) in whom thrombolysis had failed out of a total of 225 consecutive patients admitted to hospital with suspected AMI.MethodsIn suitable patients, thrombolysis with ‘accelerated’ recombinant tissue-type plasminogen activator (rtPA) was initiated. Patients in whom thrombolysis was unsuccessful were randomised within 4 hours of onset of symptoms into two groups. Unsuccessful thrombolysis was defined as failure to show any sign of reperfusion after administration of the first 65mg of rtPA, or as recurrence of pain and ST-segment elevation within 30 to 60 minutes of the end of full thrombolysis (100mg of rtPA). The 42 patients in group 1 (GPIIb/IIIa) stopped thrombolysis (if still being administered) and received treatment with an intravenous bolus plus infusion of GPIIb/IIIa antagonists (abciximab or tirofiban or eptifibatide) plus heparin according to the Thrombolysis in Myocardial Infarction (TIMI)-14 schedule and aspirin. The 42 patients in group 2 (placebo) received the full dose of rtPA, even if there was no sign of reperfusion, and placebo together with standard heparin and aspirin. Patients without signs of reperfusion were immediately referred for rescue revascularisation.ResultsIn group 1 (GPIIb/IIIa), 22 patients received rtPA 65mg and 20 patients received rtPA 100mg. 39 patients showed rapid reperfusion (4 ± 3 min) on treatment with GPIIb/IIIa antagonists, and only one required rescue percutaneous transluminal coronary angioplasty (PTCA). Coronarography after 12 to 72 hours demonstrated patency of the infarct-related artery in the 39 patients who showed rapid reperfusion. In group 2 (placebo), no patients showed reperfusion and all received rescue PTCA. Three patients in the GPIIb/IIIa group and two in the placebo group experienced bleeding-related adverse effects. Patients receiving GPIIb/IIIa antagonists showed a nonsignificantly reduced requirement for stent treatment and a reduction of angina at 30 days after treatment compared with the placebo group.ConclusionThese preliminary data suggest the possibility of using GPIIb/IIIa receptor antagonists in patients with failed thrombolysis after AMI, with an acceptable increase in bleeding risk. We consider the demonstration of the safety of this combination as the most important result of this study.

Immediate versus delayed facilitated percutaneous coronary intervention : A pilot study

The study was aimed to investigate the outcomes in patients initially successfully treated pharmacologically and immediate PCI <2 hours, and in patients initially successfully treated with pharmacological therapy and delayed PCI (12-72 hours). All patients had to have successful reperfusion, to receive the combination of a standard abciximab infusion plus half dose rtPA. Similar results were observed in both groups. Delayed PCI group showed a favorable trend in restenosis and bleedings (ns) and a significant reduced angiographic evidence of thrombus formation in IRA. Our very preliminary data suggest the safety and possible use of delayed facilitated PCI in patients with STEMI. The studied patients have successful reperfusion and TIMI-3 flow and our data may not apply to patients with TIMI 0-2 flow.

Relationship between ACE-DD polymorphism and diastolic performance in healthy subjects

Background—The ACE-D allele has been associated with cardiovascular disease. The study evaluates the relationship between the ACE-ID genotypes and diastolic function in healthy subjects after 6 years of follow-up. Methods—Two hundred and seventy-five healthy volunteers aged 25–55 years had normal physical examination, 12-lead ECG, acceptable echocardiographic windows and echocardiogram at entry. Venous blood was drawn for DNA analysis. Results—Two hundred and forty-two subjects completed 6 years of follow-up. Three genetically distinct groups were obtained: ACE-DD group (n=71, 26F/45M, mean age 48±7 years); ACE-ID (n=115, 39F/76M, mean age 40±7 years); and ACE-II (n=56, 20F/36M, mean age 47±6 years). Significant differences in E/A ratio were found between ACE-DD and ACE-ID, and ACE II (p=0.028, <0.0001, 0.0001), respectively. After 6 years, echocardiography showed a significant reduction of E/A ratio in the ACE-DD group, p=0.0001. Conclusion—The data suggest that ACE-DD is associated with deteriorating myocardial diastolic properties.

Comparison of Ticlopidine and Aspirin versus Clopidogrel and Aspirin after Percutaneous Coronary Interventions in High-Risk Patients

Background: Studies have shown that ticlopidine and clopidogrel in association with aspirin reduce the short- and long-term incidence of major adverse coronary events in patients undergoing stent implantation. Furthermore, clopidogrel seems to show a better side-effect profile than ticlopidine, and recent evidence supports its efficacy in long-term prevention in high-risk patients. Methods: From May 2002 to December 2003, 428 consecutive patients with 1st coronary event underwent a percutaneous coronary intervention (PCI) for non-ST elevation myocardial infarction. All patients received a glycoprotein IIb/IIIa inhibitor and were randomized in double-blind fashion to ticlopidine (500 mg/day) + aspirin or clopidogrel (75 mg/day) + aspirin before PCI. After 48– 72 h, PCI with stent implantation was performed and the treatment was continued for 6 months. Two groups were obtained. The clopidogrel group contained 214 patients (146 M/68 F), mean age 61.3 ± 11.8 years, and the ticlopidine group contained 214 patients (150 M/64 F), mean age 60.7 ± 10.5 years. A protocol that included clinical follow-up at 1, 3 and 6 months was used. Results: Both groups were comparable in baseline characteristics. We observed 14 cases of non-cardiac side effects in the clopidogrel group in the first 30 days after discharge. The ticlopidine group showed 20 non-cardiac side effects (not significant). None of the patients died during the follow-up. Both groups were similar in number of diseased vessels and number of stents. During follow-up (180 days), 48 patients from the clopidogrel group and 44 from the ticlopidine group showed reocclusion in vessels treated with percutaneous transluminal coronary angioplasty (p value not significant). In addition, we observed that reocclusion was mostly evidenced in the first 90 days (44 from the clopidogrel and 40 from the ticlopidine group). In the remaining time (90 days), we observed only 4 cases of reocclusion from the clopidogrel and 4 cases from the ticlopidine group. Conclusion: Our data suggest that ticlopidine or clopidogrel associated with aspirin determine similar effects.

Safety and tolerability of abciximab in patients with acute miocardial infarction and failed thrombolysis

AIMnThe aim of this study was to evaluate glycoprotein IIb/IIIa receptor inhibitor effectiveness in AMI patients with unsuccessful thrombolysis.nnnMETHODSnEighty-four patients hospitalised within 4 h of symptom onset were randomised (single blind) into two groups. Regardless of the group, placebo or GP IIb/IIIa inhibitors were administered to patients who did not present with reperfusion signs 30 min after starting thrombolysis and 30-60 min after the end of full thrombolysis in patients with pain recurrence and ST-segment elevation. Reperfusion was assessed by the creatine kinase peak occurring within 12 h, by the observation of rapid ST-segment reduction (50-70% within 1 h) in 12-lead ECG continuous monitoring, by the rapid regression of pain and by the development of early ventricular arrhythmias. Group 1 (GP IIb/IIIa) (42 patients) received treatment with GP IIb/IIIa inhibitors i.v., heparin according to TIMI-14 trial and aspirin during failed thrombolysis or after 30-60 min effective thrombolysis because of pain recurrence and ST segment elevation. Group 2 (placebo) (42 patients) received a full dose of rtpA (100 mg) and placebo either during failed thrombolysis or after 30-60 min effective thrombolysis because of pain recurrence and ST segment elevation and standard heparin treatment and aspirin.nnnRESULTSnThirty-nine group 1 (GP IIb/IIIa) patients showed rapid reperfusion (6 +/- 4 min) after abciximab treatment; 22 patients received rtpA 65 mg and 20 patients received rtpA 100 mg and subsequent GP IIb/IIIa inhibitor treatment. Coronarography, performed after 3-12 h, showed patency of infarct related artery (IRA) in 39 patients whose clinical picture was suggestive of rapid reperfusion during administration of a bolus of GP IIb/IIIa inhibitors. No group 2 (placebo) patients showed reperfusion and they were submitted to rescue PTCA.nnnSIDE EFFECTSnFour cases in the GP IIb/IIIa group and two cases in placebo group (major bleeding). Patients receiving GIIb/IIIa inhibitors showed a reduced incidence of stent treatment (ns) and a significant reduction of events (angina) within 30 days of treatment.nnnCONCLUSIONnOur data suggest the possibility of using IIb/IIIa glycoprotein receptor inhibitors in patients with AMI and failed thrombolysis. The increased risk of bleeding was acceptable. The most important results were the safety of this combination.

Characteristics of coronary microcirculatory function in patients with Takotsubo syndrome

BackgroundnTakotsubo syndrome (TS) is a recently described cardiac syndrome whose pathogenesis is still unclear. We investigated the characteristics of coronary microcirculatory function in patients with TS through the analysis of the TIMI frame count (TFC) compared to normal subjects and with to subjects with microvascular angina (MA).nnnMethodsnWe enrolled 71 TS patients (F:M =69:2, mean age of 65.27±9.53 years), 70 controls (F:M =34:36, mean age of 56.63±13.5 years) and 71 patients with MA, (F:M =69:2, mean age of 65.9±9.2 years). The assessment of the microcirculation was carried out through the TFC.nnnResultsnmicrocirculation was significantly altered in patients with TS compared with healthy controls [left anterior descending coronary artery (LAD) 25.16±6.91 vs. 17.30±3.76, P<0.001; circumflex artery (CX) 25.48±6.10 vs. 17.05±4.60, P<0.001; right coronary artery (RCA) 26.43±8.95 vs. 15.74±4.27, P<0.001, average TFC in TS 25.70±5.34 vs. 16,70±3.26, P<0.001). A TFC >20 frames was able to discriminate TS patients from controls with a specificity of 88.57% and sensitivity of 85.92% (AUC 0.927, P<0.0001). Microvascular dysfunction was diffuse in TS as well as in MA and slightly more severe in this last (mean TFC in MA 28.25±9.3 vs. 25.7±5.34 in TS, P<0.046).nnnConclusionsnCoronary microcirculation in TS patients is diffuse and milder compared to MA patients. Cut-off values >20 frames discriminate between patients with normal microcirculation and patients with TS.