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The use of Eye Tracking (ET) has been investigated as an auxiliary mechanism to diagnose Autism Spectrum Disorder (ASD). One of the paradigms investigated using ET is Joint Attention (JA), which refers to moments when two individuals are focused on the same object/event so that both are aware that the focus of attention is shared. The computational tools that assist in the diagnosis of ASD have used Image Processing and Machine Learning techniques to process images, videos and ET signals. However, the JA paradigm is still little explored and presents challenges, as it requires analyzing the gaze trajectory and needs innovative approaches. The purpose of this article is to propose a model capable of extracting features from a video used as a stimulus to capture ET signals in order to verify JA and classify individuals as belonging to the ASD or Typical Development (TD) group. The main differential in relation to the approaches in the literature is the definition and implementation of the concept of floating Regions of Interest, which allows monitoring the gaze in relation to an object, considering its semantics, even if the object presents different characteristics throughout the video. A model based on ensembles of Random Forest classifiers was implemented to classify individuals as ASD or TD using the trajectory features extracted from the ET signals. The method reached 0.75 accuracy and 0.82 F1-score, indicating that the proposed approach, based on trajectory and JA, has the potential to be applied to assist in the diagnosis of ASD.

Autism Spectrum Disorder (ASD) is a developmental disorder that persistently impairs communication and social interaction, with a high degree of clinical heterogeneity. The fact that the diagnosis is based on clinical observation which requires therapy expertise, interviews with parents and application of questionnaires, it contributes to delaying the diagnosis until school age. The study of anthropometric measures in individuals with ASD and individuals in typical development (TD) showed there are some differences between the two groups. However, there is a lack of computational tools to assist in the acquisition and analysis process of these measures. This paper proposes a computer-aided medical decision support system that, given a child’s facial image captured by a digital camera, can discriminate between the two groups, ASD and TD, thus helping in the diagnosis. We defined a protocol for image acquisition and preprocessing, tested and compared methods for dataset balancing, dimension reduction and classification. The best results were obtained by a SVM classifier with 86.2% accuracy. Once the proposed model is based on facial images, it has the potential to facilitate early diagnosis of ASD.

Background. In recent years, pathophysiology of aortic stenosis (AS) has been considered as a possibly active inflammatory process, but its determinants remain unclear. Calcium tissue deposition observed in dilaysis patients have been linked to low level of Fetuin-A, a powerful inhibitor of ectopic calcification. It is thus suspected to play a role in development of aortic stenosis. Purpose. To assess correlation between Fetuin-A level and AS progression in a prospective cohort of AS patients, COFRASA (clinicalTrial.gov_number_NCT00338676) and GENERAC (clinicalTrial.gov_number_NCT00647088). Methods. A comprehensive clinical evaluation and Fetuin-A plasma level measurement was performed at baseline. AS severity was evaluated at baseline and yearly thereafter using echocardiography (mean pressure gradient (MPG)) and computed tomography (degree of aortic valve calcification or AVC). Annual progression was calculated as [(final measurement - baseline measurement)/follow-up duration] for both MPG and AVC measurements. Results. We enrolled 296 patients with at least 1 year of follow-up. Mean age was 74±10 years, 217 (73%) were men. Mean Fetuin-A level was 0.55±0.15 g/L. After a mean follow-up of 3.0±1.7 years, no correlation was found between AS progression and Fetuin-A level, using either MPG (r=0.015, p=0.82) or AVC (r=0.014, p=0.82). This was also true when comparing patients with lower level of Fetuin-A (≤0.53 g/L, the median in our cohort) with patients with higher level(+3±5 mmHg/year (median 2, [0-5] vs +4±4 mmHg/year (median 2, [1-6]) p=0.06, and +205±290 AUC/year (median 122, [32-269]) vs +240±310 AUC/year (median 145, [50-313], p=0.24). This was true also after adjustment for baseline severity and valve antomy. Conclusions. In our prospective cohortot of AS patients we found no impact of Fetuin-A on both hemodynamic and anatomic AS progression. Despite strong capacity to inhibit ectopic calcium deposition, Fetuin-A plasma level seems to have minor influence on AS progression.

Background Arterial stiffness is associated with increased risk for cardiovascular disease. The purpose of this study is to investigate the arterial stiffness and myocardial deformation in patients with poorly controlled diabetes mellitus type 2 before and after glycemic control by optimal medication. Methods In 50 patients with uncontrolled type 2 diabetes(age:52±10years)and 25 controls of similar age and sex and no atherosclerotic risk factors we measured at baseline and 6 months after glycemic control a) carotid-femoral pulse wave velocity(PWVc m/sec-Complior SP ALAM),central systolic blood pressure(cSBP -mmHg),augmentation index(AI%), of the aortic pulse wave(ArteriographTensioMed) b)S',E'(m/sec)andE'/A'of mitral annulus by Tissue Doppler c)LV longitudinal strain(GLS-%),systolic(LongSr-l/sec)and diastolic(LongSrE-l/sec)strain rate, twisting(Tw-deg),peak twisting(Tw)and untwisting(unTw-deg/sec)velocity using speckle tracking echocardiography.The degree of LV untwisting was calculated as the percentage difference between peak twisting and untwisting at MVO(%dp PeakTw-UntwMVO)and between peak twisting and untwisting at peak and end of the mitral inflow E wave d)perfusion boundary region(PBR- micrometers)of the sublingual arterial microvessels(ranged from 5-25 micrometers)using Sideview,Darkfield imaging(Microscan,Glycocheck).Increased PBR is considered an accurate index of reduced endothelial glucocalyx thickness because of a deeper RBC penetration in the glucocalyx e) Flow mediated dilatation(FMD) of the brachial artery and percentage difference of FMD (FMD%). Results Compared to controls,diabetics had higher PWVa(10.3±2.2 vs. 8.1±1.9), AI(27.9±15 vs. 19.4±14.7), PWVc(11.8±3.2 vs. 8.8±1.3),cSBP(136±20 vs. 119±18),PBR (2.1±0.2 vs 1.89±0.1)and lower GLS(-15±3 vs. -18±3),LongSr(-0.78±0.1 vs. -0.96±0.2),LongSrE(0.77±0.29 vs. 1.2±0.3),S',E' and E/A(p

Between 1977 and 1993, 384 breast cancer patients were followed up post-operatively every 4 or 6 months with a serum tumour marker panel (CEA-TPA-CA15-3) and the usual imaging techniques. Twenty-eight patients were treated 13.5 +/- 10 months (mean +/- s.d.) before the clinical and/or radiological occurrence of distant metastases that were suspected because of an increase in the tumour markers (patients treated 'early'). Their outcome was compared with that of 22 similar patients who were treated only after a definite radiological diagnosis was achieved (patients treated 'not early'). The median survivals from mastectomy and salvage treatment were also compared for the two groups. The groups were similar for all the major prognostic factors (menopause, staging, hormone dependency). In the group treated 'early', the lead time from the tumour marker increase to the clinical and radiological signs of metastases was significantly longer than that of the group not treated 'early' (13.5 +/- 10 vs 3.4 +/- 2.8 months respectively; P < 0.001 by unpaired t-test). For patients treated 'early', the survival curves up to 30 months after salvage treatment and up to 72 months after mastectomy showed greater survival than those for the patients treated later (42.9% vs 13.6% and 42.9% vs 22.7% respectively; P = 0.04 in both instances). These data suggest that treatment triggered by rising tumour markers before clinical and/or radiological appearance of distant metastases can be useful in prolonging both the asymptomatic interval and the duration of response of some relapsed patients. Randomized prospective trials must be encouraged to confirm these data and to better evaluate the effect on the disease-free survival (DFS) and overall survival (OS) of 'early' salvage treatment protocols.

gamma-Glutamyltranspeptidase (gamma GT) appears in serum in multiple forms; their significance and clinical utility in hepatobiliary and pancreatic diseases are still a matter of controversy. Electrophoretic separation of the multiple forms of gamma GT on agarose gel was performed in 20 alcoholic patients (six with cirrhosis and 14 with fatty liver) and the results compared with those obtained in 50 healthy volunteers, 43 patients affected with chronic hepatitis C, 36 patients with posthepatitic cirrhosis and in 52 epileptic patients on long-term anti-epileptic medication. Multiple forms of gamma GT were separated into several bands (up to 11), labelled 0a, 0b, 1a, 1b, 2a, 2b, 2c, 3a, 3b, 4a, 4b. In the alcoholic patients nine fractions were detected, and the electrophoretic pattern observed was significantly different from that observed in healthy volunteers and in patients with chronic hepatitis C or posthepatitic cirrhosis. No differences were observed in the electrophoretic patterns in the alcohol abusers and epileptic patients. In alcoholic patients significant differences were observed in the electrophoretic patterns in relation to the degree of liver injury; the electrophoretic patterns in patients with alcohol-related cirrhosis and posthepatitic cirrhosis differed significantly. The separation of multiple forms of gamma GT has high sensitivity and good reproducibility. It may be proposed as a complementary test in the diagnosis of alcoholic liver disease.

Evaluation of the biocompatibility of four different types of oxygenator (bubble, membrane, hollow fibre and ‘hybrid’) was performed on 26 patients undergoing cardiopulmonary bypass during elective coronary surgery. More platelet derangement and an increased degree of hemolysis, revealed by higher plasmatic concentration of beta-thromboglobulin, platelet factor 4 and plasmatic free hemoglobin (p < 0.05), was seen when using the bubble oxygenator. Damage to blood cells was minimal with the membrane oxygenator while the ‘hybrid’ and the hollow fibre oxygenators proved to rank at an intermediate level. Complement activation at the beginning of the cardiopulmonary bypass occurred via the alternative pathway as demonstrated by C3adesarg increase (up to nine times) without a concomitant elevation of C4adesarg. Cardiopulmonary bypass complement activation was quantitatively similar with all the oxygenators. A further activation via the classical pathway occured in all the patients after protamine injection. Consistent differences as far as clinical and biological effects exist among the various commercially available cardiopulmonary bypass apparatus; our study provides guidelines for the evaluation and selection of devices which might reduce postoperative sequelae.

Orthostatic intolerance is the most serious symptom of cardiovascular deconditioning induced by microgravity. However, the exact mechanisms underlying these alterations have not been completely clarified. Several methods for studying the time series of systolic arterial pressure and RR interval have been proposed both in the time and in the frequency domain. However, these methods did not produce definitive results. In fact heart rate and arterial pressure show a complex pattern of global variability which is likely due to non linear feedback which involves the autonomic nervous system and to "stochastic" influences. Aim of this study was to evaluate the degree of interdependence between the mechanisms responsible for the variability of SAP and RR signals in subjects exposed to head down (HD). This quantification was achieved by using Mutual Information (MI).

Orthostatic intolerance, induced by microgravity exposure, has been hypothesized to be related to a disorder of the autonomic control of the cardiovascular system. Non-invasive measurement of Heart Rate Variability (HRV) have been used as a valuable tool to characterize the ability of the autonomic system to modulate the cardiovascular function by analyzing the spontaneous fluctuations of arterial pressure and heart period on a beat-to-beat basis. Concerning this, conflicting results have been reported on the heart rate and blood pressure variability responses during exposure to microG. These differences seem to be due to different experimental designes used. Moreover, the different behavior of normal subjects in response to orthostatic stress after HD, i.e. Symptomatic (S) or Non Symptomatic (NS), could play some role in producing these discrepancies [correction of dicrepancies]. In this study we suggest the analysis of "magnitude" or "volatility" as a new method to study HRV variability. The volatility is a measure of the beat-to-beat excursion capability of the heart, regardless to its direction (positive or negative): the higher the volatility, the greater the excursion. The aim of the present study was to examine R-R volatility before and after 4 hours of HD -6 degrees in normal subjects.

To assess the relationship between baseline left ventricle function, functional reserve and resting myocardial perfusion in patients with acute myocardial infarction (AMI). After AMI the presence of dysfunctioning but viable myocardium plays a determinant role in clinical outcome. Regional ventricular function was evaluated by echocardiography both in resting conditions and during dobutamine infusion (10 microg/kg/min). Perfusion was assessed by magnetic resonance imaging in a single slice approach where the first pass of an intravenously injected bolus of gadolinium-based contrast agent was followed through six regions of interest within the myocardium. In each patient a region with normal function was used as reference and the cross-correlation coefficient (CCC), which described the myocardial perfusion relatively to the reference region (CCC = 1 means equivalent perfusion), was obtained for the other five myocardial regions. Twenty-two patients were enrolled into the study. Sixty-one segments had normal function and normal perfusion (CCC = 0.92+/-0.23). The perfusion deficit was more marked in the 29 regions with resting akinesia-dyskinesia than in the 20 hypokinetic regions (CCC = 0.71+/-0.45 vs. 0.84+/-0.23; p0.05). Out of the 29 regions with resting akinesia-dyskinesia the 13 segments which showed functional improvement following dobutamine had a higher resting perfusion than the 16 segments which were unresponsive to dobutamine (CCC = 0.83+/-0.32 vs. 0.61+/-0.52, p0.05). Similarly, out of the 20 regions with resting hypokinesia the 11 segments having functional reserve showed an higher resting perfusion than the segments which did not (0.96+/-0.21 vs. 0.69+/-0.19; p0.05). Early after AMI, the perfusion deficit reflects the severity of the mechanical dysfunction. In regions with baseline dyssynergy resting perfusion is, in general, higher when contractile reserve can be elicited by stress-echo.

We assessed the contribution of difference in duration of pulmonary venous and mitral flow at atrial contraction (ARd-Ad) for prognostic stratification of patients with left ventricular (LV) systolic dysfunction.Although pulmonary venous flow (PVF) variables may supplement mitral flow patterns in evaluating left ventricular (LV) diastolic function, their value to the prognostic stratification of patients has not been investigated.Pulsed wave Doppler mitral and PVF velocity curves were recorded in 145 patients (mean age: 70 years) with LV systolic dysfunction secondary to ischemic or nonischemic cardiomyopathy who were followed for 15 +/- 8 months. In 38% of patients, PVF signal was enhanced by the intravenous (IV) administration of a galactose-based echo-contrast agent. Based on E-wave deceleration timeor = or130 ms and ARd-Ad, patients were grouped into restrictive (group 1, n = 40), nonrestrictive with ARd-Ador =30 ms (group 2, n = 55) and nonrestrictive with ARd-Ad30 ms (group 3, n = 50).During follow-up, 29 patients died from cardiac causes and 28 were hospitalized for worsening heart failure (HF). On multivariate Cox model, ARd-Ador =30 ms provided important prognostic information with regard to cardiac mortality and emerged as the single best predictor of cardiac events (cardiac mortality, hospitalization). The 24-month cardiac event-free survival was best (86.3%) for group 3; it was intermediate (37.9%) for group 2; and it was worst (22.9%) for group 1 (p0.0002 group 1 vs. 3; p0.0005 group 2 vs. 3; p0.0003 group 1 vs. group 2).Assessment of ARd-Ad exhibited an independent value in the prognostic evaluation of patients with LV systolic dysfunction. Moreover, it contributed to identify patients at low, intermediate and high risk of cardiac events.

A simple two-compartment model was used to study the effects of water exchange on the signal produced by an inversion recovery prepared rapid gradient-echo sequence during the first passage of a low dose of an intravascular contrast agent. Water exchange at intermediate rates of exchange (1-10 Hz) between the vascular and extravascular spaces caused the form of the signal changes during the first pass to be dependent on both the fractional sizes of the vascular and extravascular compartments and on the exchange rate. Unless the effects of exchange are minimized by using a very short inversion time, parameters such as the peak height and area under the curve will be affected by regional and/or pathological variations in the exchange rate and the size of the vascular fraction. The mean transit time (MTT) is, however, less affected by water exchange. Experimental first-pass data produced by intravascular low-dose injections of iron oxide particles were studied in five pigs at 0.5 T. The MTT as derived from the first-pass curves, without deconvolution with the arterial input function, was well correlated with the myocardial blood flow (MBF) as measured using radioactive microspheres (r = 0.70, n = 52, P0.01). Other first-pass parameters such as the peak height or area under the curve exhibited either a poorer, or no, correlation with the MBF. The data suggest that the MTT of the first pass of an intravascular contrast agent may be a robust, quantitative method for assessing myocardial blood flow in patients.

Rational prognostic algorithm should be developed considering the logical progression of the information as it becomes available to the physician, with clinical data first, ECG data second and stress imaging data last. The aim of the present study was to assess in a clinically realistic fashion the relative prognostic value of exercise electrocardiography test (EET) and dipyridamole-echocardiography test (DET) early after first acute uncomplicated myocardial infarction.Five hundred and forty-seven in-hospital patients (age = 56 +/- 9 years) with recent clinically uncomplicated first myocardial infarction, baseline echocardiographic findings of satisfactory quality, interpretable ECG and capability to exercise underwent a resting 2D echocardiogram, a DET and an EET at a mean of 10 days from the infarction and were followed up for 16.2 +/- 11 months. During the follow-up, there were 17 cardiac deaths, 19 non-fatal myocardial infarctions and 49 unstable angina. When cardiac death was considered as the only significant event, with multivariate analysis, peak dipyridamole Wall Motion Score Index was the only significant predictor (chi 2 = 5.66; p = 0.013; relative risk estimate = 4.7; confidence intervals = 1.35-16.08). In presence of a negative exercise electrocardiography test for both chest pain and electrocardiographic criteria, the death rate was 2%.DET provides stronger information in comparison with historical and EET variables. However, a negative maximal EET is sufficient to identify a very low risk subset in whom additional testing may not be warranted.

Aim of this study is to evaluate the presence of peculiar personality traits in patients with acute myocardial infarction as compared with normal subjects.The Sixteen Personality Factor Questionnaire (16 PF) by Cattell (D form) is administered to 654 patients (558 males, 96 females) hospitalized for acute myocardial infarction in 16 coronary care units and to 398 normal subjects (261 males, 137 females). The diagnosis of myocardial infarction is made according to the presence of at least two of the following criteria: prolonged chest pain, elevation of CPK and CPKMB (twice the upper normal values), Q wave on the electrocardiogram. The normality of the control group is assured by specific exclusion criteria (cardiac or psychiatric disease, metabolic and endocrine disease, continued therapeutic treatment for any organic disease, or continued assumption of hypnotic and/or anxiolytic drugs).In comparison with the control group, infarcted males result significantly different for factors C, N, Q1, Q4 (p0.001), for factors B, O (p0.01) and A, H, I (p0.05). Females with myocardial infarction differ significantly for factors C, O and I (p0.05). Four second-order factors is obtained from Cattell's 16 PF by factorial analysis: QI (anxiety), QII (extroversion), QIII (sensitivity), QIV (superego strength). The infarcted population shows statistically significant differences compared with controls: infarcted males show higher QI (p0.001) and lower QII and QIII (p0.05) while infarcted females have higher QI (p0.05).These differences confirm that peculiar personality traits can be found in patients with acute myocardial infarction. In particular, infarcted males are emotionally unstable, anxious, rigid and depressed, and have problems in communication with others; infarcted females differ from the normal population for being emotionally unstable, anxious and for having a less flexible mental disposition. The higher anxiety level in patients with acute myocardial infarction may be related to the neuroticism that, in other studies, has been often found to be associated with cardiovascular disease. In conclusion, with respect to the normal population, patients with acute myocardial infarction appear to be anxious introverts, with conflictual personality.

This study was conducted to assess the feasibility, safety and prognostic value of dipyridamole echocardiography in elderly patients recovering from an uncomplicated acute myocardial infarction in a subset analysis performed on the patients entered in the subproject "residual ischemia" of the Echo Persantine Italian Cooperative Study (EPIC).Coronary heart disease accounts for two thirds of all deaths in the age group65 years, and50% of all patients admitted to the hospital with acute myocardial infarction are65 years old. The prognostic value of dipyridamole-induced left ventricular dysfunction was clearly established in patients evaluated early after acute infarction.In a subgroup analysis of the Echo Persantine Italian Cooperative Study (EPIC), we assessed the value of dipyridamole echocardiography in predicting cardiac events in 190 elderly (or = 65 years) patients (age 68.4 +/- 3.3 years, range 65 to 78; 147 men and 43 women) evaluated early (mean 10 days) after uncomplicated acute myocardial infarction and followed up for 14 +/- 9.8 months.There was no major side effect during dipyridamole echocardiography. A positive test result occurred in 85 patients (44.7%). During follow-up, there were 62 events (14 cardiac deaths, 7 nonfatal reinfarctions, 21 cases of class III or IV angina and 20 revascularization procedures). Of these 62 events, 44 occurred among 85 patients with positive dipyridamole echocardiography and 18 among 105 patients with negative dipyridamole echocardiography (52% vs. 17%, p0.001). Spontaneous events (death, reinfarction, angina) occurred in 31 patients with positive and in 11 with negative dipyridamole echocardiography (36% vs. 10%, p0.001). Hard events (myocardial infarction or death) occurred in 14 patients with positive and 7 with negative dipyridamole echocardiography (16% vs. 6%, p0.05). Death occurred in 11 patients with positive and in 3 with negative dipyridamole echocardiography (13% vs. 3%, p0.01). The positive predictive value of positive dipyridamole echocardiography and negative predictive value of negative dipyridamole echocardiography as related to the occurrence of all events in the follow-up period (death, reinfarction, angina, revascularization procedures) were 52% and 83%, respectively. The relative risk (that is, the relative risk of occurrence of future cardiac events in the group with positive dipyridamole echocardiography compared with that in those with negative dipyridamole echocardiography) was 3 for all events and 4.4 for death.Dipyridamole echocardiography was well tolerated by elderly patients and proved to be very effective in prognostic stratification early after uncomplicated acute myocardial infarction, even when only survival was considered.

Any new diagnostic test should follow a pathway similar to that of a new drug, from initial studies in highly selected populations under strictly controlled conditions, up to large scale multicenter trials more likely to represent the true performance of the test in the clinical arena.To evaluate the capability of prognostic stratification of high dose (up to 0.84 mg/kg over 10') dipyridamole-echocardiography test (DET) early after an acute myocardial infarction in a "phase IV" study, based upon 11 different echocardiographic laboratories, all with established experience in stress echo and fulfilling quality control requirements for stress echo readings.Nine-hundred twenty five patients were evaluated after a mean of 10 days from an acute myocardial infarction and followed up for a mean of 14 months.During DET, one major adverse reaction occurred, consisting of a prolonged ischemia resistant to aminophylline and nitrates, and progressing to small uncomplicated reinfarction. In 11 patients the lower dipyridamole dose (0.56 mg/kg over 4') gave limiting side effects. Patients were followed up for 14 +/- 9.9 months (range = 1.53). During the follow-up, there were 34 deaths and 37 non-fatal myocardial infarctions; 104 patients developed class III or IV angina, and 149 had coronary revascularization procedures (bypass or angioplasty). Considering all spontaneous events (angina, reinfarction and death), the most important univariate predictor was the result of DET (chi-square = 45.8). With a Cox analysis, echocardiographic positivity, age and sex were found to have an independent and additive value. Considering survival (and therefore death as the only event) age was the most meaningful parameter, followed by the Wall Motion Score Index during dipyridamole (chi-square = 12.1); among other parameters, the resting Wall Motion Score Index was a significant predictor of death. By Cox analysis, age (relative risk estimate = 1.02) and Wall Motion Score Index during dipyridamole (relative risk estimate = 14) showed an independent and additional prognostic value. In particular, considering death only, the event rate was of 2% in patients with negative DET, 4% in patients with high dose positive DET and 7% in patients with low dose positive DET.Dipyridamole echocardiography is feasible and safe early after uncomplicated myocardial infarction and allows an effective risk stratification on the basis of the presence, severity, extent and timing of the induced dyssynergy. In particular, the risk of death doubles in patients with high dose positivity and almost quadruples in patients with low dose positivity.

Observational data prospectively collected permit the examination of a complex set of decisions, including the decision not to perform any stress testing. Patients with or without previous myocardial infarction admitted for coronary evaluation and not submitted to any stress testing because of clinical reasons are at a higher risk for subsequent death. For prognostication, no test has been better validated than exercise electrocardiography: it can identify patients at low and high risk for future cardiac events among those without symptoms, with typical chest pain, and with previous myocardial infarction. In patients with triple-vessel disease, the results of exercise also allow those at low and high risk to be recognized. Both exercise radionuclide angiography and 201Tl scintigraphy (the latter in larger patient populations) have also demonstrated significant prognostic value on patients with or without previous myocardial infarction. Neither one has shown superiority to the other in prognostication. So far, they have been considered the only viable alternatives to exercise electrocardiography stress testing for diagnosis and prognostication. However, their costs limit their extensive application. Preliminary data suggest that intravenous dipyridamole echocardiography can be used for both diagnosis and prognostication of coronary artery disease; moreover, the prognostic information derived from dipyridamole echocardiography testing seems independent of and additive to that provided by exercise electrocardiography. Further prospective studies on larger patient populations are needed to better define the prognostic value of dipyridamole echocardiography testing.

Incidence and mechanisms of psychological stress-induced myocardial ischemia were investigated in a population of 63 patients using mental arithmetic. Fifty subjects (group 1) were selected as a consecutive population of ischemic patients with electrocardiographic documentation of ischemia at rest, on effort, or both. Mental arithmetic induced increases in heart rate, blood pressure, and rate-pressure product in all patients. Transient ischemic electrocardiographic changes occurred in 22 patients (44%; positive mental arithmetic), the majority of whom had both resting and exercise angina. In negative mental arithmetic tests, peak rate-pressure product was always lower than that achieved during exercise (mean +/- SD, 11.9 +/- 3 versus 21.3 +/- 5, p less than 0.01). Of the 22 patients with positive mental arithmetic tests, ischemia occurred in only six, at a rate-pressure product equal to or more than the one achieved during exercise (21.1 +/- 5 versus 19.4 +/- 4, p less than 0.01), suggesting an increase in myocardial O2 demand exceeding the limited increase in flow; in the remaining 16 patients, rate-pressure product values were significantly lower (14.8 +/- 3 versus 22.7 +/- 6, p less than 0.01), suggesting a primary reduction in coronary blood flow that is probably related to an increase in coronary tone. To assess the possible site of such a vasoconstriction, the effect of mental arithmetic on large coronary artery diameter was tested in 13 additional unselected patients (group 2) undergoing coronary angiography for a chest pain syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

This study assessed both group and individual variability of ECG exercise stress test in patients with effort angina. Forty-five untreated patients with typical effort angina, without evidence of spontaneous angina, with a positive exercise stress test (ST depression greater than 0.2 mV) and angiographically documented coronary artery disease were studied. Four multistage exercise stress tests were performed, two in the morning and two in the afternoon, on two consecutive days. Forty-four patients completed the protocol for a total of 176 exercise stress tests. For each exercise stress test the following parameters were analyzed: time to 0.15 mV ST segment depression (time to ischemia); rate-pressure product at ischemia (ischemic threshold); slope and intercept of the linear regression between rate-pressure product and time of exercise. Silent effort ischemia was largely prevalent: 21 patients (48%) experienced chest pain in all four tests, but only seven showed a consistent time relationship between pain and ECG changes. Symptomatic patients did not appear different from the asymptomatic ones in terms of clinical and angiographic data. When group data were analyzed for each parameter the four exercise stress tests appeared reproducible. In contrast, when individual variability of each parameter was computed as the percentage difference between range (maximum--minimum) and maximal value obtained in the series of four exercise stress tests, a large variability was detected. Variability of time to ischemia, was 27.2 +/- 17.4%. This resulted from a random combination of variability in ischemic threshold (19.1 +/- 9.2%), slope (28.4 +/- 12.8%) and intercept (22.7 +/- 10%).(ABSTRACT TRUNCATED AT 250 WORDS)

In the diagnosis of ischemic heart disease, long-term ECG recording has several distinct advantages. It allows one to relate patient symptoms to cardiac disturbances and to detect asymptomatic events, reveals the possible ischemic genesis of arrhythmias, and it is the most suitable method to assess the acute and chronic effectiveness of treatment and the evolution of the disease. In spite of these advantages, Holter monitoring has several limitations: the analysis of a single lead, is responsible in most systems for the low sensitivity in detecting ischemia occurring in unexplored regions; the period of 24-48 hours may not be sufficient for screening patients due to the unpredictable spontaneous variability of the disease; a common standard of analysis is still lacking even if the European Communities concerted action in Ambulatory Monitoring could represent the solution to this problem. Nevertheless the role of Holter monitoring appears essential in the ambulatory screening of patients with suspected ischemia for a better characterization of patients with ascertained myocardial ischemia, and for the evaluation of treatment and of the evolution of the disease.

Platelet function (aggregation by ADP, adrenaline, collagen and circulating platelet aggregates) before, during and after dietary induction of hyperuricemia (ribonucleic acid, 3 g/day) was studied in five healthy volunteers to assess the relationship between uric acid level and platelet function. In the same subjects, during a second period of ribonucleic acid diet, the acute and chronic effects of a hypo-uricemizing agent, allopurinol, were assessed. No significant correlation was detected between platelet function and uricemia either in the absence or in the presence of pharmacological treatment with allopurinol. On the basis of these results, the well known relationship between uric acid levels and ischemic heart disease does not appear to be mediated by an exaggerated platelet function.

A retrospective study of 107 patients who sustained an acute myocardial infarction (AMI) during hospitalization was undertaken to assess the early prognosis of Q wave AMI (55 patients, group 1) and no-Q wave AMI (52 patients, group 2). Forty-one patients in group 1 and 31 in group 2 had documented ischaemia at rest in the period preceding AMI. The incidence of pre-infarction ischaemic attacks was similar in Q wave AMI compared with non-Q wave AMI (average daily incidence per patient 3.1 +/- 4.3 vs 3.0 +/- 4.3). A 'crescendo' pattern of pre-infarction angina was rarely observed in both groups. The incidence of post-infarction ischaemia (documented in 28 patients of group 1 and in 28 of group 2) was greater, but not significantly, in group 2 (average daily incidence per patient 1.0 +/- 2.6 vs 1.4 +/- 3.2). All patients with pre-infarction ischaemia sustained infarction in the same territory. AMI in group 1 was always symptomatic while 12 AMIs in group 2 were totally asymptomatic. Fifty patients from group 1 and 27 from group 2 were on therapy while AMI developed. Twenty-one patients from group 1 showed life threatening arrhythmias (ventricular tachycardia, ventricular fibrillation, third degree AV block or asystole) during AMI; of these, 14 did not survive the arrhythmias; they all had signs of left ventricular failure. Only one patient from group 2 had runs of ventricular tachycardia, unrelated to AMI but during pre- and post-infarction ischaemia. The overall mortality rate of Q wave AMI was 29% while no deaths occurred in the non-Q wave AMI.(ABSTRACT TRUNCATED AT 250 WORDS)

This study explores the effects on some hematological parameters of a low-dose aspirin regimen (50 mg/day) versus a conventional aspirin treatment with reported antithrombotic efficacy (324 mg/day), in patients with acute myocardial infarction. Fifteen patients were randomized into 3 equal groups receiving 50 mg or 324 mg aspirin or placebo, daily for 21 days. Compared with placebo, bleeding time was significantly and similarly prolonged with both aspirin doses (+ 71 +/- 22% and + 69 +/- 20%, mean +/- S.D.). Aspirin 50 mg/day suppressed arachidonate-induced platelet aggregation and secondary phase aggregation after ADP and adrenaline. Collagen aggregation was inhibited by 44 +/- 15%. In no case were differences in the antiplatelet effects of the two doses observed. The effects of 50 mg/day persisted without attenuation during the observation period. Platelet thromboxane B2 generation during arachidonate-induced aggregation was inhibited by 95 +/- 2 and 99 +/- 1% compared to placebo group after 50 and 324 mg/day, respectively (P between doses less than 0.05). No change was observed with any treatment in coagulation time, prothrombin time or plasma thromboplastin time. Thus, in patients with acute myocardial infarction, the antiplatelet effects of aspirin 50 mg/day are stable over time and superimposable on those of 324 mg/day. The antithrombotic efficacy of aspirin 50 mg/day remains to be tested clinically.

Twenty-four patients with effort angina and positive exercise stress test performed four control exercise stress tests, two tests while taking propranolol (240 mg/day) and two tests while taking verapamil (320 mg/day), in a randomized crossover sequence. For each test the following parameters were measured: time and rate-pressure product at ischemia; intercept and slope of the linear regression between rate-pressure product and minutes of exercise. Group analysis showed that both drugs improved time to ischemia significantly and to the same extent. However, eight patients responded preferentially to verapamil in contrast to 12 patients on propranolol. The remaining four patients responded equally to both drugs. In verapamil responders, verapamil increased time to ischemia by decreasing intercept and increasing rate-pressure product at ischemia. In these patients, propranolol did not increase time to ischemia because of a marked decrease in rate-pressure product at ischemia. In propranolol responders the significant increase in time to ischemia during propranolol was the result of a decrease in intercept and slope. The ineffectiveness of verapamil in these patients was related to a slight decrease in intercept without any increase in rate-pressure product at ischemia. The preferential response to one of the two drugs could not be predicted on the basis of clinical and angiographic features. In conclusion, in patients with effort angina, medical treatment should be personalized and based on a direct and objective verification of a drug's efficacy since different mechanisms can modulate exercise tolerance.

Cardiac pain is a key symptom for diagnosis of myocardial ischemia in man, even if a minority of transient myocardial ischemic episodes are painful. A multiparametric monitoring approach - associating non-invasive and invasive monitoring techniques during transient myocardial ischemia with and without pain - allows to achieve a clinical diagnosis and obtain information about the pathophysiology of the anginal syndrome.

Following the casual observation reported by one anginal patient of ours, of improvement of its claudicatio intermittens with application of isosorbide dinitrate ointment directly on the leg suffering pain, we undertook a study to assess the possible use of the drug in peripheral vascular disease in a group of 10 patients suffering of a severe form of claudicatio intermittens. The effect of the drug was tested 1) by the subjective valuation of the patient itself 2) by treadmill stress tests performed at constant rate. In this case were used as reference parameters the distance walked without any symptoms and the maximal distance reached by each patient. The treadmill stress test was performed in basal condition and after longterm administration of isosorbide dinitrate ointment 100 mg three times a day for 30-45 days. In 5 patients the control test was repeated twice in different days to evaluate the reproducibility of the measure that resulted good, while other 5 patients performed the test one hour following the application of the drug in order to assess a possible acute effect of the drug that was not present in any patient. All the patients noted an improvement in their walking capacity but only after 15-20 days of treatment. In basal condition the distance walked without any symptoms by the patients was on the average m. 51 (+/- 52) and the maximal distance reached was m. 143 (+/- 111), while after the treatment were m. 151 (+/- 136) and m. 384 (+/- 203) with a difference highly significative (p less than 0.05 and p less than 0.01 respectively). From our data although preliminary, it is apparent that longterm local application of isosorbide dinitrate is effective in the treatment of patients with peripheral vascular disease and that the action of the drug seems to be related to a local effect.

We evaluated the long-term therapy with Isosorbide Dinitrate Ointment (ISDN-O): 300 mg daily on the painful leg area in 20 male patients (pts) affected by Intermittent Claudication. The efficacy of the treatment was assessed on the basis of the subjective evaluation of pain threshold (daily diary) and objectively by repeated treadmill stress tests performed by each patient at a constant speed, selected according to the severity of symptoms, and by the evaluation of changes both of the distance walked without symptoms (DWS) and of the maximal distance reached (MDR). The maximal duration of the test was 15 minutes independently from the speed. The reproducibility of treadmill tests and the acute effect of isosorbide dinitrate ointment administration were preliminarly evaluated in 2 groups of 5 patients each. The distance walked without symptoms and maximal distance reached in two control stress tests performed in two successive days were: distance walked without symptoms 37 +/- 29 vs 36 +/- 22 m (NS) and maximal distance reached 97 +/- 40 vs 98 +/- 37 m (NS). During the control period and 1 hour after the drug administration distance walked without symptoms was 34 +/- 31 vs 43 +/- 50 m (NS) and maximal distance reached 89 +/- 53 vs 97 +/- 57, (NS) respectively. In a group of 5 patients the effect of one month administration of placebo was evaluated: distance walked without symptoms was m 68 +/- 29 and m 104 +/- 62 and maximal distance reached was m 156 +/- 103 and m 188 +/- 97 basally and after 1 month of placebo (NS).(ABSTRACT TRUNCATED AT 250 WORDS)

In 40 drug-free patients 2052 episodes of transient myocardial ischemia (28% painful) were recorded by 24-h ambulatory ECG. Pain was more frequently associated with longer duration of ischemia and greater ST segment shift and with the presence of ventricular arrhythmias within the ischemic episode. Heart rate always showed a growing trend during the ischemic episode. Circadian distribution of painless ischemic episodes showed a maximum peak at 2 a.m. while the most painful attacks occurred early in the morning (6 a.m.).

While the use of the 24 hour Holter monitoring for the detection of the cardiac arrhythmias and conduction disturbances is well established, its applicability to the monitoring of the ST segment and T wave for the detection of myocardial ischemia is controversial. For these reasons the Holter monitoring is mainly confined to the detection of cadiac arrhythmias and is used in those centers where computer facilities are available. We proposed to record the electrocardiographic tape replayed at 60 times the real time on a direct recording ultraviolet oscillograph running at low speed obtaining a fast compact analogue representation of the Holter recording where the 24 hour Holter recording is compressed into cm 480 of paper. The analogue compact representation described allows an easy detection of the transient displacement of the ST segment and/or changes in the T wave amplitude and direction and/or QRS pattern all due to myocardial ischemia without the use of any expensive computer facilities.

In the diagnosis of ischemic heart disease, long-term electrocardiographic recording has several distinct advantages. It allows one to relate patient symptoms to cardiac disturbances and to detect asymptomatic events, furnishes the whole spectrum of electrocardiographic alterations accompanying ischemic attacks, reveals the possible ischemic genesis of dysrhythmias, and is the most suitable method to assess the acute and chronic effectiveness of treatment and the evolution of the disease. In addition to its valuable application in the screening and follow-up of ambulatory patients, its use in the Coronary Care Unit is of great interest, being in this context much more sensitive than visual electrocardiographic monitoring. In spite of these advantages, Holter monitoring has several limitations: the recording and replay systems are below recommended standards; the analysis of a single lead is responsible in most systems for the low sensitivity in detecting ischemia occurring in unexplored regions; the period of 24-48 hours, usually adopted for Holter monitoring, may not be sufficient for screening patients with suspected myocardial ischemia due to the unpredictable spontaneous variability of the disease; a common standard of analysis is still lacking and a reliable computerized analysis is needed to manage data overflow. In conclusion, although further research and technical developments are desired to improve reliability and data processing, the role of Holter monitoring appears essential in the ambulatory screening of patients with suspected ischemia for a better characterization of patients with ascertained myocardial ischemia, and for the evaluation of treatment and of the evolution of the disease.

In 10 patients with frequent anginal attacks admitted to CCU, 2-lead ECG Holter monitoring (H-M) was performed for a total of 10 days. The number of ischemic episodes detected by retrospective analysis of H-M was compared with the number detected on the basis of symptoms and continuous visual ECG monitoring in CCU (CCU-M) by highly trained staff. A total of 157 episodes was identified by H-M [82 ST elevation (ST), 15 ST depression (ST) and 60 t wave changes]. Only 15 of these episodes were detected by CCU-M (13 ST, 1 ST and 1 T wave changes) of which 12 were symptomatic. When 6 H-M ECGs were simultaneously displayed on an oscilloscope in real-time (as in CCU-M), one of the Authors was able to detect only 36% of the episodes, whereas the frequency reached 80% when the analysis was limited to one tape at the time. The results show the low reliability of the CCU-M in detecting ischemic attacks; this appears mainly related to the display of multiple tracings.

Aim of the study was to evaluate whether frequency of myocardial ischemic attacks at rest (IA) had any identifiable distribution during 24-hour periods. Two ECG leads were continuously recorded by an Oxford 4-24 tape recorder for a total of 148 days in 10 patients admitted to CCU because of frequent spontaneous anginal attacks. During 48 days, in absence of therapy, 682 IA were recorded (2.03 per patient per day). They showed a symmetrical bell-shaped distribution curve in the 24 hour periods with a peak occurring at 5 a.m. and 43% of IA from 0 to 6 a.m. Only 25% of IA was symptomatic with the lowest values (10%) between 2 and 6 a.m. Distribution of IA was independent from their distinctive electrocardiographic feature [ST (71%) or T changes]. During 100 days with therapy [Verapamil and/or Isosorbide dinitrate ointment) a marked reduction of episodes was observed (0.64 per patient per day), while their distribution, the incidence of different electrocardiographic patterns and percentage of symptomatic IA remained unchanged. Attenuated incidence, but inalterated distribution of IA with therapy suggest its possible effect on the threshold response of coronary smooth muscle to vasoconstrictor stimuli rather than its primary effect on pathogenetic factors.

In patients with ischemic heart disease the evaluation of regional myocardial perfusion by 133Xenon intracoronary injection using a gamma camera computer system allows the detection of regional alterations of myocardial perfusion. While at rest a minority of the patients studied shows large alterations, during pacing induced angina a severe reduction of regional myocardial perfusion can be evidenced both in initial distribution scintigrams, when the injection is performed during angina, and on the washout curves when angina is induced immediately after the injection, during the course of the washout.