Metabolic Management of Coronary Heart Disease: Adjunctive Treatment with Trimetazidine Decreases QT Dispersion in Patients with a First Acute Myocardial Infarction

Purpose. The metabolic management of ischemic heart disease represents a promising new therapeutic approach for acute coronary syndromes. Trimetazidine has been suggested to exert anti-ischemic properties on myocardium without affecting myocardial oxygen consumption or supply. The aim of this study was to investigate whether the administration of trimetazidine, as an adjunct to conventional treatment, decreases QT dispersion in patients with acute myocardial infarction (AMI). Methods and results. The study was prospective, randomized, double-blind and included 55 out of 86 consecutive patients aged 80 years, admitted with a first AMI. Excluded from the study subjects with atrial fibrillation or pacing-rhythm, bundle branch block, pericardial or valvular heart disease or cardiogenic shock. Also were excluded patients treated with inotropic and antiarrhythmic agents, except for beta blockers. Enrolled patients were randomized into 2 groups: Trimetazidine group (n = 29) and control group (n = 26). All patients were treated conventionally and, in addition, trimetazidine group patients were received trimetazidine 20 mg orally every 8 hours started after randomization and continued throughout hospitalization. The QT and QTc (corrected QT) dispersion were measured manually on 3 and 7 post-AMI days. The mean values of QT and QTc dispersion were significantly lower in trimetazidine group on both days, compared to control group: Day 3, QTD = 52 ± 24 ms vs 68 ± 30 ms (p = 0.034), QTcD = 52 ± 21 ms vs 75 ± 34 ms (p = 0.004). Day 7, QTD = 39 ± 17 ms vs 60 ± 20 ms (p < 0.0001), QTcD 40 ± 17 ms vs 62 ± 20 ms (p < 0.0001). Between days 3 and 7 the mean values of QT (p = 0.003) and QTc dispersion (p = 0.002) were decreased significantly only in trimetazidine group. An analysis with respect to the use of thrombolysis revealed that trimetazidine sub-groups had lower QT and QTc dispersion mean values on day 7, both in patients treated (p < 0.05) and non-treated (p = 0.001) with thrombolysis. Conclusions. It is concluded that trimetazidine decreases QT and QTc dispersion after acute myocardial infarction. Further investigation is needed to evaluate the mechanism and the clinical implications of this effect.     

Effects of Trimetazidine on Submaximal Exercise Test in Patients with Acute Myocardial Infarction

Background: It was demonstrated that the novel metabolic agent, trimetazidine, could lessen the incidence and severity of angina, whether used in monotherapy or combination. Although the animal studies demonstrated that trimetazidine reduces myocardial infarct size and improves recovery of mechanic function after ischemia, little is known on the potential benefits of trimetazidine in patients with acute myocardial infarction (AMI). The aim of this study was to evaluate the efficacy of trimetazidine on AMI by sub-maximal exercise test. Methods: A double-blind crossover trimetazidine versus placebo trial was carried out in 44 patients with AMI. Patients were randomly allotted into trimetazidine (23 patients) or placebo (21 patients) for 5 days and underwent an initial sub-maximal exercise test. Exercise tests according to the modified Bruce protocol were performed. Exercise end points included completion of stage II or 75% of maximum predicted heart rate whichever came first. An averaged 12-lead ECG was obtained at rest, every minute during exercise, at the onset of anginal symptoms, at the onset of 1-mm ST segment depression, at peak exercise and every 2-minute during recovery. After the initial exercise tests, study groups resumed the drugs in the opposite order for 4 to 5 days and underwent a second sub-maximal exercise test. Results: Exercise induced ST segment depression was noted in 17 patients (38.6%) receiving placebo. However, exercise induced ST-segment depression was observed in 8 patients (18.1%) taking TMZ. Positive exercise test results were significantly higher in placebo group than TMZ group (p = 0.018). Additionally, trimetazidine prolonged the time to 1-mm ST-segment depression (6.1 ± 0.5 vs 4.9 ± 0.4, p < 0.031) and exercise duration (7.2 ± 0.9 vs 5.8 ± 0.9, p < 0.025). Conclusion: Trimetazidine therapy improves the exercise capacity and reduces evidence of ischemia derived from sub-maximal post-infarction exercise testing.     

A randomized double-blind trial of intravenous trimetazidine as adjunctive therapy to primary angioplasty for acute myocardial infarction

BACKGROUND: Despite high patency rates, primary angioplasty for myocardial infarction does not necessarily result in optimal myocardial reperfusion and limitation of infarct size. Experimentally, trimetazidine limits infarct size, decreases platelet aggregation, and reduces leukocyte influx into the infarct zone. To assess trimetazidine as adjunctive therapy to primary angioplasty for acute myocardial infarction a prospective, double-blind, placebo-controlled pilot trial was performed. METHODS: 94 patients with acute myocardial infarction were randomized to receive trimetazidine (40 mg bolus followed by 60 mg/day intravenously for 48 h) (n=44) or placebo (n=50), starting before recanalization of the infarct vessel by primary angioplasty. Patients underwent continuous ST-segment monitoring to assess return of ST-segment deviation to baseline and presence of ST-segment exacerbation at the time of vessel recanalization. Infarct size was measured enzymatically from serial myoglobin measurements. Left ventricular angiography was performed before treatment and repeated at day 14. RESULTS: Blinded ST segment analysis showed that despite higher initial ST deviation from baseline in the trimetazidine group (355 (32) vs. 278 (29) microV, P=0.07), there was an earlier and more marked return towards baseline within the first 6 h than in the placebo group (P=0.014) (change: 245 (30) vs. 156 (31) microV respectively, P=0.044). There was a trend towards less frequent exacerbation of ST deviation at the time of recanalization in the trimetazidine group (23.3 vs. 42.2%, P=0.11). There was no difference in left ventricular wall motion at day 14, or in enzymatic infarct size. There was no side effect from treatment. Clinical outcomes were similar between groups. CONCLUSION: Trimetazidine was safe and led to earlier resolution of ST-segment elevation in patients treated by primary angioplasty for acute myocardial infarction.     

Improved detection of acute myocardial infarction by magnetic resonance imaging using Gadolinium-DTPA

Summary To assess the value of the paramagnetic contrast agent Gadolinium (Gd)-DTPA in Magnetic Resonance Imaging (MRI) of acute myocardial infarction (AMI), we studied 20 patients with a first AMI by ECG-gated MRI before and after intravenous administration of 0.15mmol/kg Gd-DTPA. The MRI studies were performed after a mean of 98 hours (range 15–241) after the acute onset of AMI. Spin-echo measurements (TE 30 msec) were made using a Philips Gyroscan (0.5 Tesla). After performing the baseline MRI scans, the MRI procedure was repeated every 10 minutes for up to 40 minutes following injection of Gd-DTPA. In 18 (90%) patients contrast enhancement in the infarcted myocardial areas was observed after Gd-DTPA. In these patients intensity versus region curves, derived from 9 to 11 adjacent myocardial regions of interest, showed increased signal intensities in the infarcted areas after administration of Gd-DTPA. The precontrast signal intensity ratio between infarcted and normal myocardium was 1.14±0.15 (mean±SD); the postcontrast ratios at 10 minutes were 1.41±0.21 (P <0.05), at 20 minutes 1.61±0.19 (P <0.01), at 30 minutes 1.43±0.20 (P < 0.05), and at 40 minutes 1.33±0.20 (P=NS). It is concluded that MRI using the contrast agent Gd-DTPA significantly improves the visualization and detection of infarcted myocardial areas in patients with AMI and that optimal contrast enhancement is obtained 20 minutes after administration of Gd-DTPA.     

The effects of right ventricular involvement on heart rate variability and ventricular late potentials in acute inferior myocardial infarction

Depressed heart rate variability and presence of ventricular late potentials in acute myocardial infarction are associated with a poor prognosis. Although it is known that the abnormalities vary according to anterior or inferior location of acute myocardial infarction, the relationship with right ventricular acute myocardial infarction is not clear. The effects of right ventricular myocardial infarction on heart rate variability and ventricular late potentials are studied. The study was performed with a total of 46 patients (38 males; aged 56 +/-13 yr, range, 33 to 70 yr). Twenty-six patients had isolated inferior myocardial infarction while 20 patients had accompanying right ventricular involvement. For all patients, ambulatory Holter recordings between 24 and 48 hours following myocardial infarction, echocardiography in first 48 hours, and signal-averaged electrocardiography with submaximal exercise at average day 6 (range, 5 to 8 days) were performed. Heart rate variability and signal-averaged electrocardiography recordings were repeated after discharge (average, 39 days). During the first 24 to 48 hr, time domain parameters (SDNN1 and SD1) were significantly lower (SDNN1: 62 +/- 17 vs 100 +/- 20 ms, p = 0.001; SD: 37 +/- 10 vs 50 +/- 16 ms, p = 0.03) in patients with isolated inferior MI than in those with right ventricular involvement, whereas root-mean-square voltage (RMS-SD1) showed no significant difference in both groups (28 +/- 7 vs 35 +/- 8 ms). In post-discharge heart rate variability recordings, there were no significant differences (SDNN2: 86 +/- 13 vs 95 +/- 15 ms; SD2: 48 +/- 11 vs 57 +/- 13 ms; RMS-SD2: 32 +/- 14 vs 35 +/- 9 ms). In pre-discharge tests, the mean value of low-amplitude signals (LAS1) was higher (26 +/- 9 vs 33 +/- 11 ms, p = 0.03) in patients with isolated inferior myocardial infarction than in those with right ventricular involvement, while other signal-averaged electrocardiography parameters were not significantly different (filtered QRS: 102 +/- 5 vs 105 +/- 10 ms, RMS-40(1): 44 +/- 13 vs 26 +/- 10 microV; incidence of ventricular late potentials: 23% vs 30%, p = NS, respectively). In post-discharge tests, all of signal-averaged electrocardiography parameters were similar in both groups (filtered QRS2: 112 +/- 12 vs 114 +/- 8 ms, LAS2: 28 +/- 9 vs 32 +/- 13 ms, RMS-40(2): 36 +/- 10 vs 34 +/- 11 microV, and frequency of ventricular late potentials2: 23% vs 30%, p = NS). These data suggest that right ventricular involvement in an acute inferior myocardial infarction is associated with improved heart rate variability parameters but not ventricular late potentials in pre-discharge period. However, the influence of right ventricular involvement on heart rate variability parameters fades away in the post-discharge period.     

Prognostic significance of late ventricular potentials after acute myocardial infarction

The prognostic significance of late ventricular potentials recordedfrom the body surface using high-gain amplification and signalaveraging was assessed prospectively in 160 patients (mean age56±8.3 years) after recent acute myocardial infarction(median day of study 25.5). Late potentials were recorded in 81 out of 160 patients (50.6%);a duration of less than 20 ms was observed in 33 patients (20.6%),whereas late potentials of 20 ms duration or more were presentin 48 patients (30%). The mean duration of late potentials was27 ± 16.5 ms. There was no significant correlation withthe frequency and type of spontaneous ventricular arrhythmiasduring 10–24 h Holter monitoring. The follow-up period was 7.5±3.2 months (mean ±s.D.;maximum 15.8 months). In 136 patients (85%) the course afterdischarge was uneventful. Sudden cardiac death occurred in sevenpatients (4.4%) after 3.7± 3.4 months (range 0.7–8.3months). Sustained ventricular tachycardia was documented infour cases 2.9± 1.3 months after myocardial infarction,all having late potentials. The overall incidence of ventriculartachycardia in patients with late potentials of 20 ms durationand more was four out of 48 patients (8.3%) increasing to 16.6%(three out of 18 patients) if only patients with late potentialsgreater than 40 ms were considered. Sudden cardiac death occurredin three of 79 patients (3.8%) without late potentials. In patientswith late potentials less than 40 ms duration, the incidenceof sudden death was 3.2% (two out of 63 patients), but it increasedto 11.1% (two out of 18 patients) with late potentials of 40ms duration or more. Ventricular tachycardia or sudden deathoccurred in 21.7% of patients with late potentials and anteriorwall infarction compared to 5.4% in patients with late potentialsand inferior wall infarction (P<0.05). Only one of 79 patients(1.3%) without late potentials died non-suddenly from a cardiaccause (reinfarction) compared to three of 81 patients (3.7%)with late potentials irrespective of duration. Thus, this prospective multicentre pilot study suggests thataveraging might be a promising non- invasive technique for theidentification of patients prone to ventricular tachycardiaor possibly even sudden death after recent acute myocardialinfarction.     

Association Between Parasympathetic Activity and Late Potentials at Low Noise Level

Background: Late potentials (LP) in the signal-averaged ECG represent activation of myocardial areas with slow conduction and predicts re-entrant malignant ventricular arrhythmias in coronary artery disease. Low heart rate variability, which reflects low vagal and concomitantly elevated sympathetic activation also predicts ventricular arrhythmia. This autonomic profile is associated with the presence of LP (detected at noise level 0.4 μ;V) early after myocardial infarction. In contrast, sympathetic stimulation and diminution of vagal tone influence LP parameters (detected at noise level 0.2 μ;V) in the opposite direction in healthy subjects. The aim of this study was to estimate the possible association between measures of cardiac autonomic function and LP (detected at 0.4 and 0.2 μ;V) in patients with chronic coronary artery disease. Methods: ECGs of 174 consecutive patients with angiographically documented coronary artery disease and without myocardial infarction during the last 3 months were signal-averaged to noise level 0.2 and 0.4 μ;V. LP were considered to be present if any two of the following criteria were present: signal-averaged QRS duration > 120 ms, root-mean-square voltage of the terminal 40 ms of the averaged QRS complex < 25 μ;V, and late potential duration > 40 ms. Heart rate variability was measured at rest in 5-minute ECG recordings as: the standard deviation (SD) of all RR intervals, SD corrected for RR (SD/mean RR), and the power of high frequency (HF) component (0.15–0.40 Hz). Results: One hundred seven (61%) of the patients had LP at noise level 0.2 μ;V. LPs were more frequently observed in patients with slow heart rate, high heart rate variability, and high levels of vagal activity (mean RR >; 1000 ms, SD >; 60 ms, and HF >; 100 ms²) than in patients with higher heart rate, low heart rate variability and attenuated vagal activity: 73% vs 54% (P = 0.02), 71% vs 53% (P = 0.02), 72% vs 51% (P = 0.005) for mean RR, SD, and HF power, respectively. Adjustment for possible confounding from mean RR level, gender, previous acute myocardial infarction, treatment with betablocker, and left ventricular ejection fraction did not significantly alter these associations. At noise level 0.4 μ;V 26% (45/174) had LP and the diagnosis of LP was not significantly associated with heart rate variability. Conclusions: At low noise level (0.2 μ;V) higher parasympathetic activity is associated with the diagnosis of LP. The predictive power of presence of LP diagnosed at low noise level for development of sudden cardiac death may be reduced by this association. In order to increase the predictive accuracy of LP we recommend either the use of noise level 0.4 μ;V, or identification of high arrhythmia-risk patients by a combination of the presence LP and impaired heart rate variability. However, a prognostic study is needed to further clarify this.     

No effect of stem cell mobilization with GM-CSF on infarct size and left ventricular function in experimental acute myocardial infarction

Abstract. Objectives: To evaluate the effect of bone marrowpluripotent stem cell mobilization with granulocyte-monocyte colony stimulating factor (GMCSF) on infarct size and left ventricular function, in the setting of acute myocardial infarction, with a protocol easily applicable in clinical practice. Methods: Ten pigs underwent left thoracotomy and left anterior descending coronary artery occlusion for 1 h, followed by reperfusion. After 50 min of arterial occlusion, the animals were randomly divided between treatment with placebo (Group 1) and subcutaneous GM-CSF (Group 2). The thoracotomy was closed and the animals recovered. In Group 2, GM-CSF, 20 µg/kg, was administered daily, 5 days/week, for 3 weeks. Echocardiograms were obtained at 5 and 28 days after acute myocardial infarction. At 30 days, infarct size, expressed as a percentage of the whole left ventricular mass, was measured. Results: The white blood cell count increased from 13000 ± 3338/µl to 28700 ± 4916/µl (p = 0.001) in the GM-CSF-treated group. Infarct size was 7.8 ± 6.1% in Group 1 vs 7.5 ± 7.7% in Group 2 (ns). Similarly, no significant difference was observed between the 2 study groups in any of the echocardiographic measurements made at 28 days. Conclusions: Subcutaneous GMCSF administered during the early post acute myocardial infarction period neither decreased infarct size nor improved left ventricular function. Other protocols for mobilization of stem cells and their concentration in the injured area should be developed to combine efficacy and clinical applicability.     

Angiographic Morphology Following Heparin and Aspirin Therapy in Patients with Acute Coronary Syndromes and Intracoronary Thrombus

This series included 26 patients with acute myocardial infarction (15 patients) or unstable angina (11 patients), with thrombotic lesions identified by angiography and treated with intravenous heparin (mean 8 ± 3 days, aPTT 1.5–2.5 times baseline) and aspirin (250 mg/day). A quantitative angiographic analysis was performed, and comparison of the lesion morphology before and after the antithrombotic treatment was conducted, using a computer-based analysis of the lesion contour. On average, minimal lumen diameter increased by 15.6% (1.15 ± 0.5mm to 1.33 ± 0.5mm, P = 0.02), percent diameter stenosis decreased by 10.7% (60.0 ± 18% to 53.6 ± 19%, P = 0.009), percent area stenosis decreased by 6.5% (80.0 ± 14% to 74.8 ± 16%, P = 0.05), and TIMI flow increased by 8% (2.5 ± 0.9 to 2.7 ± 0.7, P = 0.02). A significant improvement in the lesion morphology was more often observed in the right coronary artery (n = 9), than the left coronary artery (n = 16). We conclude that heparin and aspirin therapy improves the angiographic morphology and TIMI flow of thrombotic lesions in patients sustaining the acute coronary syndrome. This improvement was primarily found when the lesion was located in the right coronary artery.     

Book Review

Late potentials occurring at the end of or after the QRS complexwere recorded from the body surface by means of a high-gainECG and the signal-averaging technique in 75 patients, within24 h from the onset of symptoms of acute myocardial infarction.Late potentials were found in 20 patients (26.7%). Out of thisgroup, eight (40%) developed ventricular fibrillation. Therewas only one incident of ventricular fibrillation among 55 patientswithout late potentials (1.8%, P >0.001). The three-monthmortality after myocardial infarction was slightly higher inindividuals with late potentials: 15% vs. 11.5%, but this differencewas not statistically significant. We conclude that the presence of late potentials recorded inthe acute phase of myocardial infarction indicates a risk ofventricular fibrillation, but this was not associated with anincreased mortality rate during the three-month follow-up.     

Nitroglycerin infusion after percutaneous coronary intervention does not influence short- and long-term outcome--a prospective NAPI (Nitroglycerin Administration after Percutaneous Intervention) study

BACKGROUND: Although the benefit of nitroglycerin infusion in patients after elective coronary angioplasty has not been established, this regimen is routinely used in some centres. AIM: The Nitroglycerin Administration after Percutaneous Intervention (NAPI) study tested the efficacy of routine nitroglycerin infusion on the 1st day after percutaneous coronary intervention (PCI) in a double-blind randomised single-centre clinical trial. METHODS: We randomly assigned 200 patients scheduled for elective PCI to treatment with nitroglycerin (100 patients, age 58+/-6 years, infusion up to 100 microg/min) or placebo (100 patients, age 57+/-5 years, p=NS, NaCl 0.9%) for 12 hours after PCI. Patients with acute myocardial infarction, haemodynamic instability during PCI and known intolerance to nitrates were excluded. Patients who were randomised to the placebo group had the possibility to receive nitroglycerin infusion according to the attending physician's decision. Clinical endpoints (cardiac death, myocardial infarction, postprocedural chest pain, unstable angina and repeated PCI) were assessed in hospital and out of hospital with follow-up extended to 24 months. RESULTS: There were no differences during in-hospital stay between those receiving nitroglycerin and receiving placebo, regarding mortality (0 vs. 0%, NS), myocardial infarction (0 vs. 2%, NS), postprocedural chest pain (10 vs. 8%, NS) or repeated PCI (0 vs. 2%, NS). Similarly, 24-month follow-up also revealed no significant differences between those receiving nitroglycerin and placebo (mortality: 0 vs. 0%, NS; myocardial infarction: 4 vs. 4%, NS; repeated PCI: 10 vs. 8%, NS or CABG: 0 vs. 0%, NS). CONCLUSIONS: Routine use of intravenous nitroglycerin after elective PCI has no influence on in-hospital and long-term outcome, including cardiac death, myocardial infarction, postprocedural chest pain, unstable angina and repeated PCI.     

Effect of 48-h intravenous trimetazidine on short- and long-term outcomes of patients with acute myocardial infarction, with and without thrombolytic therapy. A double-blind, placebo-controlled, randomized trial

Aims To compare the effect of trimetazidine (TMZ) versus placeboadministered during the acute phase of myocardial infarctionon long- and short-term mortality. Methods and Results EMIP–FR (European Myocardial InfarctionProject–Free Radicals) was a prospective, double-blind,European multicentre trial in which 19725 patients, presentingsymptoms of acute myocardial infarction within the previous24h were randomized. Stratification was according to thrombolytictherapy (56%) or not (44%). An intravenous bolus injection oftrimetazidine (40mg) was given just before or simultaneouslywith thrombolysis, followed by continuous infusion (60mg.24h^–1)for 48h. Overall, no difference was found between trimetazidineand placebo for the main end-point, short-term (35-day) mortality,(P=0·98) in an intention-to-treat analysis. This wasthe result of opposing trends in the two strata. Thrombolysedpatients showed a tendency towards more short-term deaths withtrimetazidine, compared to placebo (trimetazidine: 11·3%,placebo: 10·5%, P=0·15) and non-thrombolysed patientsthe converse (trimetazidine: 14·0%, placebo: 15·1%,P=0·14). In a per-protocol analysis the beneficial effectof trimetazidine for non-thrombolysed patients became statisticallysignificant (trimetazidine: 13·3%, placebo: 15·1%,P=0·027). Conclusion Trimetazidine does not reduce mortality in patientsundergoing thrombolytic therapy; however, it might have somebeneficial effect for non-thrombolysed patients.     

Electrocardiographic associations of right precordial Q waves help to distinguish anterior myocardial infarction from aortic stenosis

Right precordial Q waves are ECG evidence of anterior myocardial infarction and can be present in patients with pathological left ventricular hypertrophy particularly caused by aortic stenosis. The aim of this study was to investigate the ECG features associated with Q waves in aortic stenosis and those in anterior myocardial infarction. We studied 16 patients with anterior myocardial infarction and 19 patients with aortic stenosis by means of ECG, echocardiography and clinical history. On the ECG, heart rate (70 +/- 20 beats/min vs. 83 +/- 20) and QT interval (380 +/- 65 ms vs. 390 +/- 50) did not differ between the two conditions. PR interval (160 +/- 15 ms vs. 185 +/- 30, P<0.05) and QRS duration (80 +/- 7.0 ms vs. 95 +/- 15, P<0.01) were both longer in patients with aortic stenosis than in those with myocardial infarction. The Q wave voltage in V1 (1.0 +/- 0.55 mV vs. 1.5 +/- 0.60) or V2 (1.3 +/- 0.5 mV vs. 1.8 +/- 0.85) and R wave voltage in V5 (0.7 +/- 0.7 mV vs. 2.1 +/- 0.9) or V6 (0.7 +/- 0.4 mV vs. 1.5 +/- 0.7, all P<0.01) were significantly less in patients with anterior myocardial infarction than in those with aortic stenosis. Q wave voltage over 1.3 mV in V1 or R wave voltage over 1.5 mV in V5 can differentiate aortic stenosis from anterior myocardial infarction with a sensitivity of 79% for each and specificities of 81 and 93.8%, respectively. Though the frontal QRS axis was similar in the two groups (28 +/- 45 degrees vs. 14 +/- 35, P>0.05), the horizontal QRS axis pointed laterally (-30 +/- 20 degrees) in aortic stenosis and posteriorly (-60 +/- 20 degrees, P<0.01) in anterior myocardial infarction. A horizontal QRS axis between zero and -45 degrees detected the presence of aortic stenosis with a sensitivity of 94.7% and a specificity of 81.3%. On echocardiography, left ventricular hypertrophy was found in most patients (94.7%) with aortic stenosis but not in those (0%) with anterior myocardial infarction. Left ventricular end diastolic dimensions (5.1 +/- 0.7 cm vs. 5.1 +/- 0.9, P>0.05) were similar in the two groups but the end systolic dimension was increased in patients with aortic stenosis (4.0 +/- 0.9 cm vs. 3.4 +/- 0.6, P<0.05). The systolic left ventricular function (shortening fraction: 23 +/- 8.0% vs. 34 +/- 7.0; Vcf: 0.8 +/- 0.26 circ/s vs. 1.3 +/- 0.26, both P<0.01) was significantly impaired in patients with aortic stenosis compared to those with myocardial infarction. In conclusion, in the presence of right precordial Q waves, the simple 12-lead ECG can provide important information on distinguishing anterior myocardial infarction from aortic stenosis. In particular, the QRS voltage in the chest leads and horizontal QRS axis can differentiate anterior myocardial infarction from aortic stenosis with high sensitivity and specificity.     

后扩张在老年急性ST抬高心肌梗死行急诊PCI中的临床应用

目的探讨后扩张在老年急性ST抬高心肌梗死行急诊PCI中的临床应用效果。方法选取2015年11月至2017年10月于我院诊断急性ST抬高心肌梗并行急诊冠脉支架植入的老年患者372例为研究对象, 其中228例患者支架后行非顺应性高压球囊后扩张为观察组, 未行后扩张者144例为对照组。术中观察无复流或慢血流发生率;随访1年,观察主要不良心血管事件发生率（MACE）,支架内血栓发生率及靶病变重建率。结果在老年急性ST抬高心肌梗死行急诊PCI患者中,与对照组相比,观察组无复流及慢血流发生率（1.8%&1.4%）差异无统计学意义（P ＞0.05）,而支架内血栓形成（0.0%&1.4%）,不良心血管事件发生率（0.9%&4.9%）及再次血运重建率减少（0.4% &4.2%）（P <0.05）,差异有统计学意义。结论老年急性ST抬高心肌梗死急诊PCI时行后扩张, 可以减少支架内血栓形成及血运重建, 减少主要不良心血管事件,对提高患者的预后意义重大。     

Use of lead adjustment formulas for QT dispersion after myocardial infarction.

OBJECTIVE--To determine whether lead adjustment formulas for correcting QT dispersion measurements are appropriate in patients after myocardial infarction. DESIGN--Retrospective analysis of QTc dispersion measurements in 461 electrocardiograms (ECGs). Data are presented as uncorrected QTc dispersion "adjusted" for a number of measurable leads and coefficient of variation of QTc intervals for ECGs in which between six and 12 leads had a QT interval that could be measured accurately. PATIENTS--Patients were drawn from the placebo arm of the second Leicester Intravenous Magnesium Intervention Trial. Some 163 patients who subsequently died and an equal number of known survivors had ECGs recorded on day 2 or 3 of acute myocardial infarction. ECGs were also available in 135 of these patients from at least 1 month postinfarct. RESULTS--The most common lead in which a QT interval measurement was omitted was aVR (n = 176), the least common lead was V3 (n = 13). The longest QTc interval measured was most usually in lead V4 (n = 72) and the shortest in lead V1 (n = 67). As the number of measurable leads decreased there was a small, nonsignificant increase in QTc dispersion from 12 lead to eight lead ECGs (mean (SD) 100 (35.5) v 109.5 (47.9) ms). Lead adjusted QTc dispersion (QTc dispersion/square root of the number of measurable leads) showed a large, significant increase when the number of measurable leads decreased from 12 to eight (28.9 (10.3) v 38.7 (16.1) ms, P < 0.001). A similar trend was seen for coefficient of variation of QTc intervals (standard deviation of QTc intervals/mean QTc interval 64.3 (2.19) v 8.45 (3.94)%, P < 0.001). CONCLUSIONS--Lead adjustment formulas for QT dispersion are not appropriate in patients with myocardial infarction. Large differences in lead adjusted QTc dispersion are produced, dependent on the number of measurable leads, for very small differences in QTc dispersion. It is recommended that QT dispersion is presented as unadjusted QT and QTc dispersion, stating the mean (SD) of the number of leads in which a QT interval was measured.     

Effects of acute administration of gallopamil on left ventricular relaxation and filling dynamics in acute myocardial infarction assessed by doppler echocardiography

Summary The purpose of this study was to assess the acute effect of an intravenous bolus of the calcium antagonist gallopamil on left ventricular diastolic function using Doppler echocardiography. Fifteen patients with acute myocardial infarction in the first Killip class and sinus rhythm were randomized to an intravenous bolus of gallopamil (50 g/kg over 5 minutes) or placebo in a crossover sequence. Doppler echocardiography was performed at baseline and 15 minutes after each bolus. No patients had received calcium antagonists or beta blockers before the study; all patients received nitroglycerin, which was withdrawn at least 2 hours before the baseline Doppler echocardiogram. The following Doppler parameters were calculated: the early (E) and late (A) peak filling velocities, the velocities ratio (E/A), the diastolic filling time-velocity integral (TVI), the peak filling rate normalized to the mitral stroke volume (nMPFR), the isovolumic relaxation time (IVRT), and the systolic flow velocity integral (SFVI). Expressing the parameters measured after a gallopamil bolus as the percent change of those measured after placebo, E, E/A, and nMPFR increased by 25.5±11.5%, 30.6±15.5%, and 19.0±12.2%, respectively (p<0.001); IVRT decreased by 13.5±7.0% (p<0.001); and TVI increased mildly by 6.9±9.9% (p=0.01). SFVI and A did not change significantly. Negligible differences were observed between placebo and baseline values. Heart rate, mean blood pressure, and left ventricular and atrial diameters did not change significantly. It was concluded that gallopamil infusion improves early left ventricular filling and relaxation in patients with acute myocardial infarction. Considering the unchanged loading conditions, this indicates an improvement in left ventricular diastolic performance.     

Characteristics of endocardial monophasic action potentials recorded from areas with fractionated bipolar electrograms in infarcted canine ventricular myocardium.

STUDY OBJECTIVE--The aim was to characterise monophasic action potentials recorded from subacutely infarcted myocardial regions, where fractionated bipolar electrograms could be obtained. DESIGN--Dogs underwent ligation of the left anterior descending coronary artery. Before and 8-12 d after ligation, monophasic action potentials and local electrograms were recorded endocardially from the apex of the left ventricle. EXPERIMENTAL MATERIAL--15 anaesthetised mongrel dogs (30 mg pentobarbitone.kg-1) were used. MEASUREMENTS AND MAIN RESULTS--Multiphasic fractionated bipolar electrograms could be recorded from infarcted sites of the left ventricle with a mean duration of 69(SD 10) ms and a mean amplitude of 3.7(1.6) mV, compared to control values of 42(7) ms (p less than 0.05) and 9.4(2.2) mV (p less than 0.05), respectively. Endocardial monophasic action potentials recorded from these areas were similar to action potentials obtained from non-infarcted sites before coronary ligation. The fractionated extracellular potentials were superimposed on the monophasic action potential upstroke. MAP90 was 189(31) ms, MAP30 138(12) ms, versus control values of 182(27) ms and 139(10) ms (NS). Monophasic action potential amplitude was significantly reduced at infarcted sites compared to control, at 26(7) mV v 38(6) mV. Histological specimens were taken to confirm that measurements were obtained from infarcted tissue. CONCLUSIONS--It is possible to record monophasic action potential in subacutely infarcted canine ventricular myocardium; this technique might help in further studies to characterise electrophysiological mechanisms of ventricular arrhythmias in chronic myocardial infarction in man.     

Effect of nitric oxide synthase inhibition on haemodynamics and outcome of patients with persistent cardiogenic shock complicating acute myocardial infarction: a phase II dose-ranging study.

AIMS: Previous studies suggested haemodynamic benefits and, possibly, mortality reduction with the use of nitric oxide synthase (NOS) inhibition in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). We assessed preliminary efficacy and safety of four doses of l-n-monomethyl-arginine (l-NMMA), a non-selective NOS inhibitor, in patients with AMI complicated by CS despite an open infarct-related artery. METHODS AND RESULTS: Patients (n = 79) were randomly assigned to a bolus and 5 h infusion of placebo or 0.15, 0.5, 1.0, or 1.5 mg/kg of l-NMMA. The primary outcome measure was absolute change in mean arterial pressure (MAP) at 2 h. Fifteen minutes after study drug initiation, mean change in MAP was -4.0 mmHg in the placebo group and 5.8 (P = 0.02), 4.8 (P = 0.02), 5.1 (P = 0.07), and 11.6 (P < 0.001) mmHg in the four l-NMMA groups, respectively (all vs. placebo). Mean change in MAP at 2 h was -0.4, 4.4, 1.8, -4.1, and 6.8 mmHg in the placebo and four l-NMMA groups, respectively (all P = NS). CONCLUSION: l-NMMA resulted in modest increases in MAP at 15 min compared with placebo but there were no differences at 2 h.     

Pharmacokinetics and Hemostatic Effects of Saruplase in Patients with Acute Myocardial Infarction: Comparison of Infusion,Single-Bolus,and Split-Bolus Administration

Saruplase, or unglycosylated, single-chain urokinase-type plasminogen activator (scu-PA) selectively activates fibrin-bound plasminogen, and is subsequently converted to its two-chain derivative tcu-PA (urokinase) by plasmin. The efficacy of a 20 mg IV bolus followed by an infusion of 60 mg over 1 hour (standard regimen) has been demonstrated in acute myocardial infarction (AMI). The Bolus Administration of Saruplase in Europe (BASE) study compared the efficacy of standard therapy, single bolus (80 mg), and split bolus (2 × 40 mg at 30-minute intervals) in AMI. In a substudy of BASE, the pharmacokinetics of total u-PA activity (amidolytic activity after plasmin treatment), high molecular weight (HMW) u-PA antigen, and tcu-PA activity were compared in patients receiving standard therapy (n = 4), single bolus (n = 4), or split bolus (n = 5). Total u-PA activity and HMW u-PA antigen were similar. The maximum concentration (C_max,, mean ± SD) of total u-PA activity was 2.2 ± 0.3 µg/mL after standard therapy, 16.3 ± 3.9 µg/mL after single bolus, and 8.2 ± 1.6 ug/mL after split bolus. The area under the concentration versus time curve (AUC) values of total u-PA activity were 1.7 ± 0.1 µg/mL*h (standard therapy), 4.0 ± 0.9 µg/mL*h (bolus), and 3.0 ± 0.7 µg/mL*h (split bolus). The dominant initial half-lives (t^1/2 ) were 7.1 ± 1.1 minutes (standard), 8.8 ± 0.8 minutes (bolus), and 5.1 ± 2.1 minutes (split bolus). Maximum plasma concentrations of of tcu-PA activity were observed at 5.2 ± 7 minutes (standard), 21 ± 10 minutes (bolus), and 42 ± 2 minutes (split bolus). C_max was lowest after standard therapy (0.6 ± 0.3 µg/mL), highest after bolus (4.2 ± 2.2 µg/mL), and approximately twice as high as standard therapy after split bolus (1.3 ± 0.8 µg/mL). After standard therapy the mean fibrinogen concentration decreased gradually from approximately 300 mg/dL to 70 mg/dL at 90 and 120 minutes. After a single bolus the fibrinogen concentration decreased below the limit of quantification within 30 minutes and remained there for at least 120 minutes. Directly after the second 40 mg dose of the split bolus, the fibrinogen levels had an accelerated and more pronounced decrease to approximately 65 mg/dL at 90 and 120 minutes. A single bolus results in very high early total u-PA activity, which accelerates the appearance of tcu-PA activity and fibrinogen consumption. The pharmacokinetics and hemostatic effects of the split-bolus regimen are more comparable with those of standard therapy.     

Late potentials and computerized averaging electrocardiogram in acute myocardial infarct: evaluation of myocardial reperfusion

Myocardial reperfusion after thrombolytic therapy in acute myocardial infarction can be directly demonstrated with coronary angiography or it can be assessed thanks to indirect markers of reperfusion, such as modifications in the "averaged" QRS complex. We assessed the presence of late potentials in 37 patients within 5 hours of acute myocardial infarction onset and evaluated their disappearance or modification after reperfusion. Signal-averaged electrocardiogram, obtained computerizing QRS complexes filtered through Simson's bidirectional filter (25-250 Hz), was serially recorded in each patient: at admission, as well as 12 hours, 3 and 10 days following urokinase and/or heparin therapy. Other indirect markers of reperfusion (incidence of ventricular arrhythmias, serum CK-MB level, ST elevation) were contemporaneously evaluated. All patients underwent coronary angiography between 6 and 83 days after acute myocardial infarction. Late potentials (Total QRS greater than 115 ms; Under 40 microV greater than 39 ms; RMS Last 40 ms less than 25 microV) were present only in 25% of patients, and they always disappeared after successful thrombolysis. On the contrary if ischemia-related vessel occlusion persisted, late potentials persisted as well or else were first recorded on the 3rd or 10th day following acute myocardial infarction. Quantitative analysis of the "averaged" QRS complex showed a statistically significant reduction in QRS duration (-9.1 +/- 12.7 ms) 3 days after acute myocardial infarction in reperfused patients (group A, n = 24), while no significant reduction in the total QRS (-1 +/- 6.7 ms) was observed in non-reperfused cases (group B, n = 13), (p less than 0.05 group A vs group B). So, 10 ms reduction in total QRS duration was a good marker of reperfusion, with specificity = 92% and sensitivity = 54%; marker sensitivity was even higher (= 79%) when coupled with serum CK-MB peak within 12 hours of therapy (diagnostic accuracy = 84%). In conclusion, even if late potentials have a low prevalence in acute myocardial infarction (25%) their disappearance correlates with myocardial reperfusion. Furthermore, a reduction in total QRS duration greater than or equal to 10 ms can itself be a good marker of successful thrombolysis.