Giorgio Maringhini

Six-Month Echocardiographic Study in Patients With Submassive Pulmonary Embolism and Right Ventricle Dysfunction: Comparison of Thrombolysis With Heparin

Introduction:The aim of this study was to assess the effect of thrombolysis versus heparin treatment on echocardiographic parameters and clinical outcome, during hospitalization and within the first 180 days after admission, in patients with first episode of submassive pulmonary embolism (SPE) and right ventricle dysfunction (RVD). Methods:Consecutive patients (age, 18–75 years) with a first episode of SPE, symptoms onset since no more than 6 hours, normal blood pressure (>100 mm Hg), echocardiographic evidence of RVD and positive lung spiral computed tomography were double-blind randomized: 1 group received 100 mg of alteplase (10-mg bolus, followed by a 90-mg intravenous infusion over a period of 2 hours), while the other group received matching placebo. In addition to alteplase or placebo, both groups received an unfractionated heparin treatment. Echocardiogram was performed at admission, at 24, 48 and 72 hours, at discharge and at 3 and at 6 months after randomization. Results:Seventy-two patients were included into the study; 37 were assigned to thrombolysis and 35 to placebo. Both groups were well matched with regard to features and clinical presentation. Thrombolysis group showed a significant early improvement of RV function compared with heparin group, and this improvement was observed also during the follow-up (180 days). The same group also showed significant reduction in clinical events during the hospitalization and follow-up. Conclusions:Our data suggest that, in hemodynamically stable patients with SPE, thrombolysis shows an earliest reduction of RVD and a more favorable trend in clinical outcome, so, it could merit consideration in SPE.

Short-Term Effects of Hypertonic Saline Solution in Acute Heart Failure and Long-Term Effects of a Moderate Sodium Restriction in Patients With Compensated Heart Failure With New York Heart Association Class III (Class C) (SMAC-HF Study)

Introduction:Hypertonic saline solution (HSS) and a moderate Na restriction plus high furosemide dose showed beneficial effects in compensated heart failure (HF), in short and long terms. The study was aimed to verify the effects of this combination on hospitalization time, readmissions and mortality in patients in New York Heart Association (NYHA) class III. Method:Chronic ischemic or nonischemic cardiomyopathy uncompensated patients with HF in NYHA III functional class with ejection fraction <40%, serum creatinine <2.5 mg/dL, blood urea nitrogen <60 mg/dL and reduced urinary volume were single-blind randomized in 2 groups: the first group received a 30-minute intravenous infusion of furosemide (250 mg) plus HSS (150 mL) twice daily and a moderate Na restriction (120 mmol); the second group received furosemide intravenous bolus (250 mg) twice a day, without HSS and a low Na diet (80 mmol); both groups received a fluid intake of 1000 mL/d. After discharge, the HSS group continued with 120 mmol Na/d; the second group continued with 80 mmol Na/d. Results:A total of 1771 patients (881 HSS group and 890 without HSS group) met inclusion criteria: the first group (881 patients), compared with the second (890 patients), showed an increase in diuresis and serum Na levels, a reduction in hospitalization time (3.5 + 1 versus 5.5 + 1 days, P < 0.0001) and, during follow-up (57 + 15 months), a lower rate in readmissions (18.5% versus 34.2%, P < 0.0001) and mortality (12.9% versus 23.8%, P < 0.0001); the second group also showed a significant increase in blood urea nitrogen and serum creatinine. Conclusion:This study suggests that in-hospital HSS administration, combined with moderate Na restriction, reduces hospitalization time and that a moderate sodium diet restriction determines long-term benefit in patients with NYHA class III HF.

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

BACKGROUND beta-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). METHODS AND RESULTS Patients 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. CONCLUSIONS Our 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.

Effects of trimetazidine administration before thrombolysis in patients with anterior myocardial infarction: short-term and long-term results.

Reperfusion may prevent or reduce the development and extent of necrosis, but may also lead to an increase in reperfusion damage. Experimental studies performed in various animal models of myocardial ischemia have demonstrated the anti-ischemic properties of trimetazidine (TMZ) and have suggested that TMZ has antioxidant properties, without any direct hemodynamic effects. Our study was aimed at investigating the effects of TMZ before thrombolysis in acute anterior myocardial infarction and included 81 patients, hospitalized within 4 hours of the onset of symptoms. Patients were randomly (double-blind) subdivided in two groups The first group (40 patients, Group A, TMZ-pretreatment), received 40 mg TMZ orally about 15 minute before thrombolysis and, subsequently, 20 mg every 8 hours. The second group (41 patients, Group B) received placebo before thrombolysis. Ventricular arrhythmias (VA) due to reperfusion were evaluated in the first 2 hours. VA occurred in 15 of patients in group A, versus 29 in group B, p < 0.05. Creatine kinase (CK) normalization time was achieved after 55.7 ± 12.5 hours in group A, versus 61.2 ± 12.1 hour in group B, p = 0.048. CK peak was 1772 ± 890 in group A vs 2285 ± 910 UI/1 in group B, (p = 0.012). In the follow-up (range 6–22 months), there were 4 deaths, two patients in each group. After 180 days from treatment, the TMZ group showed a smaller end systolic volume than the placebo group (echocardiographic data), 46.2 ± 12 and 52.8 ± 13 ml/m2, respectively, p = 0.037. Our data suggest that TMZ probably reduces reperfusion damage and/or infarct size in patients with anterior AMI subjected to thrombolysis and affects the post-AMI remodeling. Our data must be interpreted with caution because of the selection of patients. These findings require further extensive trials.

Early captopril treatment reduces plasma endothelin concentrations in the acute and subacute phases of myocardial infarction: A pilot study

It has been reported that endothelin-1 (ET-1) increases in acute myocardial infarction (AMI). Experimental studies showed that captopril administration reduces ET-1 secretion. In addition, it was reported that the increased ET-1 levels are a negative prognostic index. The study sought to verify whether captopril can reduce plasma ET levels in the acute and subacute phases of reperfused anterior AMI. Forty-five patients, hospitalized for suspected anterior AMI within 4 h from the onset of symptoms, suitable for thrombolysis (first episode), Killip class I-2, were randomized (double blind) into two groups: group A (23; seven women/16 men) received captopril (as first dose) 2-4 h after starting thrombolysis (the dose was then increased up to 25 mg every 8 h). Group B (22; five women/17 men) received placebo after thrombolysis. All the patients met the reperfusion criteria. The two groups were similar with regard to age, sex, CK peak, ejection fraction, end-systolic volume and risk factors. Plasma ET levels were measured at entry, and 2, 12, 24, 48, and 72 h after starting thrombolysis. Mean concentrations of ET +/- SD: Group A basal, 1.50 +/- 0.67; at 2h, 2.31 +/- 1.24; 12 h, 1.84 +/- 1.45; 24 h, 1.30 +/- 0.72; 48 h, o.95 +/- 0.50; 72 h, 0.60 +/- 0.15 fmol/ml; p < 0.001. Group B basal, 1.58 +/- 0.83; at 2 h, 2.38 +/- 1.35; 12 h, 2.33 +/- 1.71; 24 h, 1.80 +/- 1.41; 48h, 1.46 +/- 0.88; 72 h, 0.93 +/- 0.44 fmol/ml; p < 0.001. Difference between the two groups was significant at the beginning of the test (between 2 and 12 h, p[=]0.002). After that, the values of the plasma endothelin decreased in parallel, p < 0.001. Our data suggest that captopril affects plasma ET levels in the acute and subacute phases of AMI. Moreover, these results provide additional evidence for a beneficial effect of early captopril treatment.

Thrombolysis for massive pulmonary embolism in pregnancy: a case report.

Mortality from pulmonary embolism (PE) in pregnancy might be related to challenges in targeting the right population for prevention. Such targeting could help ensure that the correct diagnosis is suspected and adequately investigated, and allow the initiation of the timely and best possible treatment of this disease. In the literature to date only 18 case reports of thrombolysis in pregnant women with PE have been reported, and showed beneficial effects for both mother and fetus in terms of mortality and complications with acceptable bleeding risks. We present here the case of a pregnant patient with massive PE who underwent successful thrombolysis. A 26-year-old pregnant (at 24 weeks) woman was admitted 4 h after onset of sudden acute dyspnea and chest pain. An immediate electrocardiogram showed a typical S1-Q3-T3 pattern. The echocardiogram showed a distended right ventricle with free-wall hypokinesia and displacement of the interventricular septum toward the left ventricle. Thrombolysis with recombinant tissue plasminogen activator (alteplase 10 mg bolus, then 90 mg over 2 h) was administered. Pelvic examination and ultrasound showed regular fetal heart beat, and regular placental and liquid presence. No problems developed for the mother or fetus in the subsequent days or at discharge. In conclusion, in pregnant patients with life-threatening massive PE, thrombolytic therapy can be administered, and the use of echocardiographic, laboratory, and clinical data can be useful tools to achieve a rapid diagnosis and make a therapeutic decision, but additional studies need to be performed to further define its use.

Sensitivity, specificity and predictive value of the echocardiography and troponin-T test combination in patients with non-ST elevation acute coronary syndromes

Introduction: Patients with a negative troponin (TnT) result showed 1.4% mortality during a mean follow-up of 9–10 weeks. Mortality was greater in patients with an evidence of ischemic ECG changes and a negative TnT test (1.6–4.4%). Few studies have examined the efficacy of echocardiography (2DE) in patients with chest pain. The purpose of the present study was to determine the clinical utility, sensitivity and specificity of the combination of TnT levels and 2DE in patients presenting with chest pain, ST-depression, T-wave negative and no diagnostic ECG. Methods: 280 consecutive patients with chest pain and presence of ST depression, T-wave inversion, and non-diagnostic ECG, acceptable 2DE window, evidence or no evidence of alterations of the segmentary motion, and evidence and no evidence of injury, as assessed by TnT and normal value of CK-CK MB, were enrolled. 2DE, blood CK, and TnT levels were controlled at entry and subsequent samples were obtained every 4 h for the first 12 h and then every 12 h. All patients performed angiography within 12–72 from admission. PTCA or CABG were performed according to angiographic findings and left ventricular function. Results: The 280 patients (98 F/M 182), mean age 59.7 ± 11.9 years, who met the entry criteria, were divided as follows: group 1: ST-segment depression (192 patients); group 2: T-wave inversion (36 patients); and group 3: non-diagnostic ECG (52 patients). The combination of positive TnT and wall motion alterations showed a higher sensitivity, specificity and predictive values in comparison with alone TnT or 2DE. Patients, with the concordance between TnT and 2DE, were at higher risk. Patients with negative combination in all groups (94), showed a low incidence of coronary stenosis (10.6%), as well as negative 2DE alone (102 patients) (12.7%), while patients with negative TnT (128) showed higher incidence of coronary stenosis (39%), p < 0.0001. Conclusion: Our results suggest that the combination of negative TnT test and negative 2DE in patients presenting to EDs with chest pain either with ECG changes or without ECG changes is a useful tool to identify those who can be discharged safely. We think that our data are important because by the combination we can identify the high risk (when positive) patients, reduce incidence of the false negative, but mostly it allows us to identify true negative patients to discharge safely.

Advantages of immediate two-dimensional echocardiography in patients with acute cardiac ischemic events

UNLABELLED We hypothesized that the assessment of kinetic alterations on two dimensional echocardiogram (2DE) would provide greater diagnostic information than clinical symptoms and ECG changes only. The study was aimed to determine sensitivity of 2DE in patients with cardiac ischemic events and to improve the indications to thrombolysis. Three-hundred ninety-one patients (87 F; 304 M) hospitalized for suspected acute myocardial infarction (AMI), first episode, within 4 h from the onset of symptoms, suitable for thrombolysis Killip class I-II and with unstable angina (UA), were admitted in the study. Patients had to show ECG changes and alterations of segmentary motion on 2DE performed at entry, or 2DE alterations without ECG changes. The 2DE variables analyzed included right ventricular function and left ventricular systolic function. Thrombolysis was performed when 2DE and ECG changes were evidenced at the same time and when 2DE alterations without ECG changes were observed. Patients with UA treated with heparin alone were also studied. The presence of segmentary motion alterations was mandatory. RESULTS Inferior AMIs, 87 patients (60 +/- 13 years), anterior AMI, 169 patients (61 +/- 11 years); UA group subjected to thrombolysis, 87 patients (62 +/- 12 years); UA group treated with heparin, 48 patients (62 +/- 12 years). We noted only one patient false negative, and five patients false positive. Alterations of right ventricular function were observed in 24, 14 and nine patients with inferior, anterior AMI and UA, respectively. Normal ECG at entry was observed in seven, two and seven patients with inferior, anterior AMI and UA, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The combination ace-inhibitors plus canreonate in patients with anterior myocardial infarction : safety and tolerability study

BACKGROUND There is recent evidence that aldosterone (ALDO) exerts pro-fibrotic effects, acting via the mineral-corticoid receptors in cardiovascular tissues and partial aldosterone escape during ACE-inhibition treatment occurs. METHODS A double blind randomised study was performed to evaluate the feasibility, and tolerability of the administration of the 25 mg/day of canreonate plus captopril versus captopril alone in patients with anterior AMI unsuitable for thrombolysis and/or not receiving thrombolytic treatment, and unreperfused after thrombolysis. Fifty five patients hospitalised for anterior AMI,with a serum creatinine concentration <2.0 mg/dl and a serum K concentration <5.0 mmol per liter were randomised in 2 groups: Group A included 27 patients who received captopril and 25 mg i.v. of canreonate (1 mg/h for the 1st 72 h and then orally 25 mg/day. Group B (28 patients) received captopril and placebo. Ten days after admission they underwent echocardiography to determine end systolic volume (ESV), ejection fraction (EF), End diastolic diameter EDD, E/A ratio, E deceleration time (dec. time) and isovolumetric relaxation time (IVRT), E and A peak velocities. RESULTS All patients did not show patency of the infarct related artery (7-10 days after AMI) and the 2 groups were similar in regard to age, sex, diabetes, smoking habits, hypertension, CK enzymatic peak, adjuvant therapy, EF, ESV, and incidence of CABG/PTCA. One patient only showed increase of serum K>5.5 mmol/dl and creatinine >2.0 mg per liter after 10 days of treatment (group A). The mitral E/A ratio was higher in group A than group B (0.85+/-0.18 and 0.75+/-0.14) respectively, P=0.024. Creatinine, blood urea and serum K did not show significant differences between groups. No side effects were observed during the study period. The incidence of vessel diseases was similar in both groups. CONCLUSIONS Our data suggest that the combination of captopril plus canreonate in feasible in early treatment of AMI patients.

Thrombolysis plus heparin versus heparin alone in the acute phases of unstable angina: preliminary findings

Abstract Several studies have shown conflicting effects of thrombolysis in patients with unstable angina. In these trials the time between presentation with chest pain and randomization was long (12 hours to 3 days). This study compared thrombolysis and heparin with heparin-alone treatment in patients in the acute phase of unstable angina. One hundred fifty-three consecutive patients hospitalized with chest pain at rest (first episode) lasting >5 minutes but P = 0.013). Data suggest that thrombolysis plus heparin produces faster clinical stabilization than heparin alone in patients treated during the acute phase of unstable angina.