Early administration of verapamil after thrombolysis in acute anterior myocardial infarction. Effect on left ventricular remodeling and clinical outcome. VAMI Study Group. Verapamil Acute Myocardial Infarction.

BACKGROUND: The administration of verapamil during the reperfusion phase of acute myocardial infarction can reduce the extent and severity of microvessel damage and limit myocardial dysfunction. We aimed at investigating the effect of early verapamil administration on left ventricular remodeling and the clinical evolution after myocardial infarction. METHODS: Eighty-eight patients with first acute anterior myocardial infarction thrombolysed < 4 hours from symptom onset were enrolled in a multicenter, randomized, double-blind, controlled study of verapamil administration (5 mg i.v. + 2 microg/kg/min over 24 hours). Echocardiographic end-diastolic (EDV) and end-systolic (ESV) left ventricular volumes were assessed by biplane Simpson's rule. RESULTS: At 90 days, EDV in the verapamil and placebo groups was respectively 88.9 +/- 27.8 and 95.8 +/- 30.7 ml (p = 0.11), ESV was 52.6 +/- 22.7 and 57.7 +/- 25.4 ml (p = 0.18). There was no change over time in the verapamil group (day 3 vs day 90: EDV 85.0 +/- 17.7 vs 88.9 +/- 27.8 ml, p = NS; ESV 48.7 +/- 14.1 vs 52.6 +/- 22.7 ml, p = NS) while left ventricular volume increased in the placebo group (day 3 vs day 90: EDV 87.6 +/- 21.1 vs 95.8 +/- 30.7 ml, p = 0.03; ESV 52.0 +/- 16.9 vs 57.7 +/- 25.4 ml, p = 0.08). NYHA functional classes were differently distributed at 30 and 90 days (chi2 = 0.009 and 0.07), with a lower prevalence of classes II and III in the verapamil group (p = 0.03). CONCLUSIONS: The early intravenous administration of verapamil in thrombolysed patients can reduce left ventricular remodeling and NYHA functional class after acute anterior myocardial infarction.

Myocardial contrast echocardiography in acute myocardial infarction. Pathophysiological background and clinical applications.

Myocardial contrast echocardiography is a technique used in experimental and clinical settings in order to visualize the pattern of intramyocardial perfusion. In the acute phase of myocardial infarction, regional absence of flow during myocardial contrast echocardiography delineates the area at risk of necrosis, while the definitive non-perfused area expresses infarct size. Reopening the infarct-related artery, which may be achieved spontaneously by thrombolysis or percutaneous transluminal coronary angioplasty, is not a reliable indicator of intramyocardial reperfusion. If myocardial ischaemia due to coronary occlusion has been sufficiently prolonged and severe, not only myocyte viability, but also microvascular integrity is lost. Myocardial contrast echocardiography, using intracoronary injection of sonicated contrast medium, gives information about microvascular integrity and the effective presence of intramyocardial reflow. Anatomical integrity of microvasculature does not necessarily imply preserved function, and thus the microvessel vasodilating reserve may also be impaired. Myocardial contrast echocardiography has the potential to assess alterations in microvascular function, showing, in the myocardial area with reduced coronary reserve, a relatively reduced increase in echocontrast signal intensity when an intravenous vasodilator agent is administered.

34-day total fast in an adult man.

The aim of this work was to investigate the changes of cardiac performance by both electrocardiography (ECG) and echocardiography (ECHOc), in addition to anthropometric and hormonal variables before, during and after prolonged total fasting (TF) and re-feeding in an overweight adult man. Physical examination, laboratory and hormonal measurements, ultrasonographic study of body fat distribution, ECG and ECHOc study were performed before during and after 34 days of TF and after 17 days of isocaloric re-feeding. The subject was a 52-year old Caucasian who was overweight with increased abdominal fat content (BMI: 28.6; W/H ratio: 0.95) and increased levels of arterial systolic and diastolic blood pressure (SBP, DBP). HPLC measurements of urinary catecholamine levels (HPLC), ECHOc study of cardiac performance, ultrasonographic study of body fat distribution were performed. The subject starved for 34 days losing 22kg, but after that time he was compelled to re-feed because of nausea and severe vomiting. A marked ketosis (ketonuria > 1200mg/day) was already present after 6 days of TF. After 17 days of TF norepinephrine (NE) and epinephrine (EPI) urinary levels showed a two-fold and nine-fold increase respectively, but they became undetectable at the end of TF. After 17 days of re-feeding catecholamine urinary levels were similar to those measured after 17 days of TF. After both TF and 17-day isocaloric re-feeding we found a decrease of visceral fat content and W/H ratio reached the normal values for age-matched subjects (W/H ratio after TF: 0.80, after re-feeding: 0.80).(ABSTRACT TRUNCATED AT 250 WORDS)

[Assessment of viable myocardium after infarction with transesophageal echocardiography and myocardial echocontrastography]. / Valutazione del miocardio vitale nel postinfarto mediante ecocardiografia transesofagea ed ecocontrastografia miocardica.

Left ventricular recovery of dysfunctioning but viable myocardium can occur only in tissue in which both myocardial contractile reserve and microvascular integrity are preserved. Recent studies have demonstrated that both inotropic stimulating echo tests and myocardial contrast echocardiography can be used to assess myocardial viability in post-myocardial infarction patients. Therefore we performed a transesophageal and myocardial contrast echocardiographic evaluation of post-myocardial infarction patients to assess: the respective accuracy of post-extrasystolic potentiation and low-dose dobutamine (5 and 10 mcg) during transesophageal echocardiography in eliciting contractile reserve, and the potential of myocardial contrast echocardiography in predicting later functional recovery. Results of our studies showed comparable effects of low-dose dobutamine (5 mcg) and post-extrasystolic potentiation in increasing myocardial thickening while low-dose dobutamine (10 mcg) had a greater potential in eliciting residual contractility. Lastly, myocardial contrast echocardiography provided a clear spectrum of intramyocardial perfusion patterns in dysfunctioning areas but did not accurately correlate with later functional recovery as better predicted by low-dose dobutamine in the same segments. In conclusion, these methods represent the preferred choice of studying the perfusion-contraction match in viable myocardium thus playing an important role in prognostic and therapeutic strategies in myocardial infarction patients.

Detection of coronary artery disease by digital stress echocardiography: comparison of exercise, transesophageal atrial pacing and dipyridamole echocardiography.

OBJECTIVES: This study assessed and compared the diagnostic potential of exercise, transesophageal atrial pacing and dipyridamole stress echocardiography in a clinical setting. BACKGROUND: Although they have been widely studied, no data exist with regard to comparisons of these procedures in a head-to-head study in different clinical settings. METHODS: One hundred four consecutive patients with suspected coronary artery disease undergoing coronary angiography and with no previous myocardial infarction or rest left ventricular wall motion abnormalities underwent digital posttreadmill, transesophageal atrial pacing and dipyridamole echocardiography. RESULTS: Feasibility of digital exercise echocardiography was 84%; 8 of 88 remaining patients had a nondiagnostic exercise echocardiographic test (inadequate exercise or imaging). In 80 patients with feasible and diagnostic digital exercise echocardiography, sensitivity, specificity and accuracy were, respectively, 89%, 91% and 90%. Eighty of the 104 patients underwent transesophageal atrial pacing and dipyridamole echocardiography. Feasibility of the alternative stress procedures was 77% for transesophageal atrial pacing and 96% for dipyridamole. In 60 patients successfully undergoing both alternative stress procedures, sensitivity and specificity were 83% and 76% for atrial pacing and 43% and 92% for dipyridamole echocardiography, respectively. In the group of 24 patients with nondiagnostic exercise echocardiography and consequent indication to alternative stress procedures, accuracy of transesophageal atrial pacing was higher than that of dipyridamole echocardiography (73% vs. 45%, p = 0.06). CONCLUSIONS: Because of its higher diagnostic potential and additional functional information, exercise is the stress of choice when stress echocardiography is used to detect the presence of coronary artery disease. Alternative stresses can be used in patients with nondiagnostic exercise echocardiography. Transesophageal and dipyridamole echocardiography differ in feasibility and diagnostic reliability (higher sensitivity of transesophageal atrial pacing, higher specificity of dipyridamole). These characteristics must be considered when selecting procedures to be used as alternatives to exercise.

Clinical use of stress echocardiography: factors affecting diagnostic accuracy.

Stress echocardiography is frequently used for the diagnosis of coronary artery disease. Its diagnostic accuracy is strongly influenced by many variables including patient selection, type of stress procedure utilized, stress protocol, echocardiographic imaging modality, digital reviewing technology and expertise in performing and interpreting the examinations. All these must be taken into consideration when evaluating and comparing different studies presented in the literature, as well as in optimal organization (accurate selection of the appropriate stress modality and protocol execution, optimal use of technology, appropriate training of medical and non-medical personnel) of the laboratory involved in stress echocardiography.

[The Italian contribution to the application of high-technology methods to clinical trials]. / Il contributo italiano nell'applicazione di metodiche ad alta tecnologia nei trial clinici.

Clinical trials are important research tools currently used in assessing new drugs and therapeutic strategies, which are unable to produce large effects evaluable in small series of patients. We describe methodological principles of clinical trials and significant advantages in their implementation produced by using a computer network for long-distance modem transmission of echocardiographic images and clinical data. This network has been recently developed in Italy and is operative at the University of Bari and the Associazione per la Ricerca in Cardiologia. Several clinical participating centers of the CEDIM Study and PHASE Study are connected in real time to a data center via modem by a special telephone network (RFD) of the Italian State Telephone Company (SIP). We describe the configuration, main features and applicative potential of such a powerful research tool in modem clinical trial methodology.

A digital network for long-distance echocardiographic image and data transmission in clinical trials: the CEDIM (Carnitina, Ecocardiografia Digitalizzata, Infarto Miocardico) study experience.

A special computer network has been specifically designed and realized to connect 36 Italian cardiological institutions to a central core laboratory. This network, which has been created to run the CEDIM Multicenter Trial (effects of L-carnitine on left ventricular function in patients with myocardial infarction assessed by digital echocardiography), enables automatic verification, via computer, 24 hours a day, of patient eligibility criteria, randomization, transmission, and filing of real-time left ventricular echocardiographic examinations. All the investigators participating in the CEDIM trial underwent several training courses as well as dummy run procedures to achieve optimal performance of all the operational procedures required for the network to function smoothly and correctly. This paper describes the aims of this special network, its technical characteristics, and the investigator training and dummy run procedures.

On-line assessment of left ventricular function by automatic border detection echocardiography during rest and stress conditions.

A new echocardiographic system, automatic boundary detection (ABD) echocardiography, provides automatic on-line quantification of the left ventricular cavity area. To assess the potential of ABD echocardiography in measuring left ventricular dimensions and detect stress-induced changes in left ventricular function, we studied 25 patients. Thirteen were studied to compare left ventricular cavity areas and fractional area change by using 2DE and ABD echocardiography during routine studies in multiple views; 12 patients were studied during transesophageal atrial pacing by ABD-echocardiography in 4-chamber or short-axis views. End-diastolic and end-systolic left ventricular areas measured by ABD echocardiography were not significantly different from two-dimensional ones for all the echocardiographic views, except the apical 4-chamber view; fractional area change values obtained with ABD were slightly lower than 2DE ones, although not significantly. High correlation values were found between the 2 techniques for end-diastolic area (r = 0.94, SEE = 3.69 cm2), end-systolic area (r = 0.90, SEE = 4.49 cm2) and fractional area change (0.73, SEE = 9.7%); similar results were obtained for each single echocardiographic view. A decrease was found from rest to peak-pacing in end diastolic area (25.2 +/- 5.1 cm2 versus 21.1 +/- 4.3 cm2, p < 0.003), end systolic area (16.2 +/- 6.0 cm2 versus 14.8 +/- 5.3 cm2, p < 0.016) and fractional area change (38.5 +/- 12.7% versus 31.8 +/- 9.6%, p < 0.003) with a return to baseline values in post-pacing (26.3 +/- 4.3 cm2 and 17.0 +/- 5.4 cm2 and 37.3 +/- 11.3%, p < 0.003 versus peak-pacing, NS versus rest for each parameter).(ABSTRACT TRUNCATED AT 250 WORDS)

Echo-Doppler evaluation of the effects of heart rate increments on left atrial pump function in normal human subjects.

It is commonly believed that the atrial contribution to left ventricular filling increases during heart rate increments. However, the relative contribution of the pump function (atrial systole) and of the passive role (diastasis and reservoir) of the atrium to end-diastolic left ventricular filling is not well known. In order to investigate this problem, we performed a two-dimensional echo-Doppler study during right atrial pacing. Transmitral flow velocity curves were obtained by means of pulsed Doppler. Pacing was performed (1) at the lowest heart rate at which it was possible to obtain a stable capture of the atria, (2) at the heart rate at which the early and late Doppler filling waves almost completely overlapped. In both stages pacing was interrupted for a few seconds to obtain some post-pacing beats. Doppler tracing recorded at rest, during pacing and in the immediate post-pacing beats were analysed to obtain well-known parameters of atrial contribution; atrial peak flow velocity, early to atrial peak flow velocity ratio, and time-velocity integral of the atrial wave. Furthermore, in order to distinguish end-diastolic passive flow from the active contribution of atrial systole to filling, we superimposed the envelope of the last Doppler curve obtained during atrial pacing over the envelope of the first post-pacing curve. In this way the area of the atrial wave of the paced beat was divided by the mid-diastolic part of the post-pacing one into two areas, the integrals of which correspond to the active and passive atrial contribution respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Transesophageal Doppler echocardiography evaluation of coronary blood flow velocity in baseline conditions and during dipyridamole-induced coronary vasodilation.

Transesophageal echocardiography allows the evaluation of proximal coronary artery anatomy and coronary blood flow velocity (CBFV). To assess the potential of transesophageal echocardiography in evaluating CBFV and its variations induced by coronary-active drugs, we studied 15 patients by high-quality pulsed wave Doppler recordings of CBFV. In these patients, transesophageal Doppler evaluation of CBFV was performed before, 2 minutes after cessation of dipyridamole infusion (0.56 mg/kg in 4 minutes), and 2 minutes after aminophylline infusion (240 mg injected 4 minutes after cessation of dipyridamole infusion). The following CBFV parameters were evaluated at each of the three steps of the study protocol: maximal and mean diastolic velocities and maximal and mean systolic velocities. Furthermore, the following indexes of coronary flow reserve were evaluated: the ratio between maximal diastolic velocity recorded after and before dipyridamole administration and the ratio between mean diastolic velocity recorded after and before dipyridamole administration. Nine of the 15 patients had a normal left anterior descending coronary artery (group A), whereas the remaining six had significant (less than or equal to 75%) stenosis (group B). In group A patients, all CBFV parameters increased significantly during dipyridamole infusion and returned to near baseline values after aminophylline infusion. In group B patients, on the other hand, none of the CBFV parameters increased after dipyridamole infusion. Dipyridamole/baseline maximal diastolic velocity and mean diastolic velocity ratios were, respectively, 3.22 +/- 0.96 and 3.04 +/- 0.88 in group A and 1.46 +/- 0.45 (p less than 0.01 versus group A) and 1.48 +/- 0.49 (p less than 0.01 versus group A) in group B patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the effects of gallopamil in patients with effort angina by transesophageal atrial pacing two-dimensional echocardiography.

Transesophageal atrial pacing (TAP) 2D echocardiography was performed after placebo (P) and gallopamil (G) (0.03 mg/kg iv) in 12 patients with stable, reproducible, effort angina. If compared to P study, during G the following changes were observed: 3 out of the 12 patients did not experience angina, time to ST-1mm increased from 5.3 +/- 1.3 to 6.6 +/- 1.6 min (p less than 0.05), wall motion score was improved both at 130 b/min (15.3 +/- 4.1 drug P, 17 +/- 4.8 drug G, p less than 0.01) and at 150 b/min (10.9 +/- 5.7 drug P, 12.8 +/- 6.3 drug G, p = 0.07). In conclusion, gallopamil has a beneficial effect on atrial pacing induced ischemia: it increases pacing time to ischemic threshold and reduces during ischemia the extent of dysfunctional myocardium.

[Evaluation of coronary anatomy and coronary circulation by transesophageal echocardiography]. / Valutazione dell'anatomia e del flusso coronarico mediante ecocardiografia transesofagea.

UNLABELLED: Nowadays the anatomy and coronary flow can be evaluated by means of various methods requiring cardiac catheterization. Transesophageal echocardiography is a new diagnostic method with great potential (excellent technical quality, stable positioning of the transducer, no lung interposition). Because of its potential we have used transesophageal echocardiography on a number of patients undergoing coronary angiography in order to investigate its reliability in estimating the anatomy and coronary flow. From the anatomical point of view 3 aspects were identified: absence of alterations affecting the vessel being explored (Criterion A); presence of non-stenotic calcific wall plaques (Criterion B); presence of stenotic calcific plaques (Criterion C). The percentage of visualization of the left main artery, the left anterior descending and the circumflex was 87%, 78% and 76% respectively. The criteria described showed varying reliability depending on the coronary portion being considered. Using the pulsed Doppler, during the transesophageal study, we obtained an adequate recording of the velocity profile of the left anterior descending in 28/37 patients. After dipyridamole infusion all velocity parameters (diastolic and systolic mean and maximum velocities) increased significantly in those patients with left anterior descending without stenosis, while remaining practically constant in those patients with significant stenosis of the left anterior descending artery. In particular the ratio between the maximum diastolic velocity recorded after dipyridamole and the velocity recorded immediately before infusion was significantly greater in those subjects with normal left anterior descending than in those with significant stenosis of the left anterior descending artery. CONCLUSIONS: transesophageal echocardiography offers new prospects in studying anatomic alterations and flow patterns of the proximal part of the left coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS)

Errors in measurements of stroke volume for invasive and echo-Doppler evaluations of valvular regurgitant fractions. Clinical evaluation and computer simulation.

The aim of this study was to compare cardiac catheterization (CATH) with 2D echo-Doppler (ED) in clinically evaluating the stroke volumes (SV) needed to calculate aortic and mitral regurgitant fractions (aortic and mitral SV for the ED method, thermodilution and angiographic SV for the CATH). As there is no 'gold standard' for this kind of measurement, only subjects without valvular regurgitation were considered. In these subjects, though the two SV measurements needed to calculate the regurgitant volume should have been identical, there was, in fact a difference due to the systematic and random errors of the methods. We calculated the mean value and the standard deviation of this difference in a series of patients without valvular regurgitation in order to obtain an estimate of both systematic and random errors. In 20 patients studied by ED a difference of 11.9 +/- 16.7 ml was found. In 36 patients studied by cardiac catheterization the difference was 19.6 +/- 20.1 ml. A significant systematic error was found for both ED and the invasive method; The transmitral SV tended to be larger than the aortic and the angiographic SV larger than that obtained by thermodilution. To try to determine the extent to which the random errors could be attributed to the reproducibility of the measurements, we carried out computer simulations. The SVs of 50 000 hypothetical patients were randomly generated and then attributed a random error calculated on the basis of the variability of the CATH (thermodilution 4%, angiography 10%) and the ED measurements (aortic annulus 6%, mitral annulus 18%, mitral time velocity integral 10%, aortic time velocity integral 8%).(ABSTRACT TRUNCATED AT 250 WORDS)

Doppler echocardiographic evaluation of the effect of atrial pacing-induced ischemia on left ventricular filling in patients with coronary artery disease.

Very little is known about the effects of acute myocardial ischemia on left ventricular filling. Previous studies of these effects have been of limited value because they were performed with 1) imaging techniques that, like cineventriculography or radionuclide ventriculography, do not allow beat to beat monitoring of left ventricular filling throughout the entire ischemic attack; and 2) exercise, which, even if effective in inducing myocardial ischemia in patients with coronary artery disease, also considerably shortens cycle length, thus leading to additional nonischemic filling alterations. To overcome these limitations, left ventricular filling was studied by means of Doppler echocardiographic evaluation of transmitral flow velocities before and immediately after rapid atrial pacing in 17 patients. Eight patients had coronary artery disease but did not develop ischemia (ST depression greater than or equal to 1.5 mm) during atrial pacing (Group 1) whereas nine had coronary artery disease and developed ischemia during atrial pacing (Group 2). No differences were observed from rest to postpacing in any of the filling variables considered in Group 1 patients. In contrast, a significant rearrangement of left ventricular filling occurred during ischemia in Group 2 patients.(ABSTRACT TRUNCATED AT 250 WORDS)