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Background The fundoscopic examination of hypertensive patients, which is an established hypertension-related target organ damage (TOD), tends to be underutilized in clinical practice. We sought to investigate the relationship between retinal alterations and left atrium (LA) volumes by means of real-time, three-dimensional echocardiography (RT3DE), which is the most pivotal predictor of diastolic dysfunction. Methods Our population consisted of 88 consecutive essential hypertensive patients (age 59.2 ± 1.2 years, 53 females) without overt cardiovascular disease. All subjects underwent a fundoscopy examination and were distributed into five groups according to the Keith-Wagener-Barker (KWB) classification. Comprehensive transthoracic echocardiographic and RT3DE measurements were performed to assess LA volumes and phasic functions. Results The four groups (KWB grades 0-4: including 26, 20, 26, and 16 patients, respectively) did not differ with regards to age, gender, or metabolic profile. There were no significant differences between groups with regards to parameters reflecting left ventricle (LV) systolic function and diastolic dysfunctions in conventional echocardiography, except isovolemic relaxation time (IVRT) and deceleration time (DT). Nevertheless, patients in the higher KWB category had higher values of LA volumes (LA maximal volume, LA minimal volume, preatrial contraction volume, LA total stroke volume, LA active stroke volume, p< 0.001) regarding RT3DE (table 1). There is also a significant relationship between preatrial contraction volume and duration of HT (r: 0.67, p

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

OBJECTIVE To evaluate the predictive value of resting heart rate (RHR) for cardiac and total mortality in a large population of patients referred for coronary angiography with an extended follow-up, stratified in four subpopulations according to gender and age (50th percentile corresponding to 67 years).We studied 3559 subjects (2603 males, age: 66 ± 11 years, mean ± SD), obtaining patient data from the Institute electronic databank which saves demographic, clinical, instrumental and follow-up data of patients admitted to our department.During a mean follow-up period of 35 ± 25 months, 296 (8%) patients died; there were 173 (5%) cardiac deaths. In female patients irrespective of age, RHR (≥ 76 bpm, 75th percentile) did not appear predictive for cardiac death. In females, RHR was predictive for overall mortality after multivariate adjustment only in those aged ≥ 67 years (hazard ratio (HR) 1.7, 95% confidence interval (CI) 1-2.8, p ≤ 0.05). In male patients aged67 years, RHR remained as an independent predictive factor for overall mortality at the multivariate analysis (HR 2.5, 95% CI 1.5-4.2, p0.001), and as an independent predictor for both cardiac mortality (HR 1.8, 95% CI 1.2-2.7, p0.01) and total mortality (HR 1.6, 95% CI 1.2-2.3, p0.01) in male patients over 67 years.The current study suggests that the prognostic importance of RHR may differ according to the patient's gender and age, suggesting significant differences in cardiovascular physiopathology between female and male patients.

Background: Amiodarone protects patients with left ventricular systolic dysfunction (LVSD) against serious arrhythmias, but it also has numerous side effects on non-cardiac organs, such as the thyroid. Indeed, amiodarone may inhibit the peripheral conversion of T4 into T3. Pathologically reduced serum levels of T3 — the so-called “low T3 syndrome” (LOWT3) — increase mortality in patients with LVSD and not on amiodarone. Aim: The aim of the study was to examine the relationship between thyroid hormone status, amiodarone therapy, and outcome in a population with LVSD. Material/subjects and methods: A total of 2344 patients with LVSD and free of overt hyper- and hypothyroidism were enrolled. The population was divided into 4 groups: group 1 (LOWT3 and amiodarone therapy, no.=126), group 2 (isolated amiodarone therapy, no.=74), group 3 (isolated LOWT3, no.=682), group 4 (controls, no.=1462). Results: Kaplan-Meier curves showed, after a mean follow-up of 31 months, increased total and cardiac mortality in groups 1 (30% and 20%, respectively), 2 (23%, 11%), and 3 (22%, 12%) compared to group 4 (total mortality log-rank 82.8, pa

A reduced standard deviation of RR intervals (SDRR) predicts increased mortality in groups of survivors of myocardial infarction. Like SDRR, the correlation dimension (D2) describes variation within a sampled time series, but uniquely it reveals 1) the epoch's geometric structure and 2) the degrees of freedom of the generator. These unique features may be more sensitive predictors of mortality than SDRR. We developed a new algorithm for estimating D2 (i.e., the "point-D2"), tested it with known data, and found that it had greater accuracy for finite data than other published algorithms. Analysis of RR intervals from eight conscious pigs undergoing acute occlusion of the left anterior descending coronary artery revealed a drop in the point-D2 from a control mean and standard deviation of 2.50 +/- 0.81 to 1.58 +/- 0.64 during the first minute of ischemia (p less than 0.01) and to 1.07 +/- 0.18 during the last minute preceding ventricular fibrillation (p less than 0.01). Partial occlusions (50-90% reduction of coronary blood flow) evoked point-D2 reductions only 25-30% of control (p less than 0.01). The point-D2 means were correlated between pigs with the magnitude of the respiratory sinus arrhythmia (p less than 0.01), but during ischemia this correlation was replaced by one between the standard deviation of the point-D2s and SDRRs. Because the simultaneous reduction in the mean point-D2 and its standard deviation to 1.07 +/- 0.18 occurred in every case, was unique to the few minutes preceding ventricular fibrillation, and never reached these low values during other conditions in which it was reduced, we conclude that the point-D2 may be an accurate prospective predictor of mortality within the individual subject.

The study of new patient record (PR) models, advanced enough to help caregivers producing and updating clinical texts, can significantly contribute to improve health care. Such innovative concepts, leading toward the realisation of the active PR, can be extended up to reduce in many instances the physician-patient gap. In this framework the authors' study tackles a basic question of the above process, that is the standardisation of medical language as used in generating a PR. The extent of the problem suggested the authors to start studying a specific section of the PR, the Holter monitoring data, possibly to be used as a paradigm of the whole PR. A controlled medical vocabulary (UMLS) drives the construction of an entity-relationship (ER) diagram, needed to determine the set of Holter monitoring data and the relationships among them. Performance evaluation shows that this approach reliably mimics meaningful clinical statements.

The conception, project realisation and updating of hospital information systems (HISs) rely on specific standardisation procedures. Particularly important is the momentum that technology is giving to the production of computer-assisted clinical documentation. Developing such a task, which includes issues like specific diagnostic reports as well as a total clinical record, requires making explicit the syntactic and semantic relationships among the data that describe the patient's health. Our study tackles the realisation of a knowledge-based clinical record designed as a combination of modules depending on a set of main medical concepts. We have heuristically defined the knowledge base's content, which has a frame-based structure, through the self-organising map (SOM) technique. We have used the SOM approach for its intrinsic capability of grouping the words of a text according to the semantic categorisations of the natural language. A set of 30 reports, referring to patients afflicted with cardiac diseases and written in the Italian language, gives us the experimental setting that we have used to train the SOM and to obtain the knowledge base. The lists of words which activate the different nodes of the SOM are assumed as frames of the required knowledge base. Performance evaluation shows that this method gives us a representation of the medical knowledge that is efficient for producing meaningful clinical sentences. Moreover, this approach is of general interest: in fact, it works independently of the language used for writing clinical documents.

The safety of ergonovine/ergometrine stress testing for coronary vasospasm when performed outside the cath lab has vigorously been questioned. The aim of this study was to assess the value of ergonovine/ergometrine stress testing performed in the echo lab.We retrospectively reviewed the data prospectively collected in the echo lab of the Institute of Clinical Physiology of Pisa (Italy) from January 1, 1985, to October 1, 1998, on 478 tests performed on 464 patients with either ergonovine or ergometrine stress echo testing. By selection, all patients had history of chest pain, consistent with vasospastic angina, negative or ambiguous exercise stress testing, and normal or near normal resting left ventricular function. Ergonovine or ergometrine maleate was injected up to a total cumulative dosage of 0.35 mg, under continuous 12 lead ECG and two-dimensional echo monitoring.There were no death, myocardial infarction, ventricular fibrillation or III degree atrioventricular block. One patient had non-sustained ventricular tachycardia associated with transient ST segment elevation 30 min after the test. Two patients had II degree atrioventricular block, associated with positive echocardiography test and promptly reversed by nitrate administration. Transient regional myocardial dysfunction occurred in 74 patients (15%). Limiting ischemia-independent side effects were present in 13 patients (3%): hypotension in 1, arterial hypertension in 5, nonsustained ventricular tachycardia in 2, and nausea/vomiting in 5. The overall feasibility was 97%.Pharmacological stress echocardiography with either ergonovine or ergometrine is highly feasible and can be safely performed in the echo lab in properly selected patients in whom coronary vasospasm is suspected. It is often the only way to document coronary vasospasm otherwise missed by conventional noninvasive stress test and even by coronary angiography.

To study the acute effects of insulin on autonomic control of cardiac function, we performed spectral analysis of heart rate variability and measured cardiac dynamics (by two-dimensional echocardiography) in 18 obese (BMI = 35 +/- 1 kg.m-2) and 14 lean (BMI = 24 +/- 1 kg.m-2) subjects in the basal state and in response to physiological hyperinsulinemia (1 mU.min-1.kg-1 insulin clamp). In the lean group, insulin promptly (within 20 min) and consistently depressed spectral powers, both in the low-frequency and high-frequency range. These changes were twice as large as accounted for by the concomitant changes in heart rate (68 +/- 2 to 70 +/- 2 beats/min). At the end of the 2-h clamp, stroke volume (67 +/- 4 to 76 +/- 9 ml.min-1) and cardiac output (4.45 +/- 0.21 to 5.06 +/- 0.55 l.min-1) rose, whereas peripheral vascular resistance fell. The low-to-high frequency ratio increased from 1.7 +/- 0.2 to 2.3 +/- 0.3 (P0.01), indicating sympathetic shift of autonomic balance. In the obese group, all basal spectral powers were significantly lower (by 40% on average) than in the lean group, and were further reduced by insulin administration. The low-to-high frequency ratio was higher than in controls at baseline (2.4 +/- 0.4, P0.03), and failed to increase after insulin (2.2 +/- 0.3, P = ns). Furthermore, obesity was associated with higher resting stroke volume (89 +/- 5 vs. 67 +/- 4 ml.min-1, P0.01) and cardiac output (6.01 +/- 0.31 vs. 4.45 +/- 0.21 l.min-1, P = 0.001) but lower peripheral vascular resistance (15.1 +/- 0.8 vs. 19.2 +/- 1.1 mmHg.min.L-1, P = 0.002), whereas mean arterial blood pressure was similar to control (90 +/- 2 vs. 86 +/- 2 mmHg, P = not significant). We conclude that physiological hyperinsulinemia causes acute desensitization of sinus node activity to both sympathetic and para-sympathetic stimuli, sympathetic shift of autonomic balance, and a high-output, low-resistance hemodynamic state. In the obese, these changes are already present in the basal state, and may therefore be linked with chronic hyperinsulinemia.

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.

We evaluated the performance and analytical parameters of a one-step magnetic IRMA kit for the measurement of myosin in serum. The method uses two monoclonal antibodies selected for their high affinity to the heavy chains of human ventricular myosin. The first antibody is coupled to a magnetic solid phase and the second one is labeled with 125I. The working range of the IRMA (range of myosin concentrations measured with an imprecision10% CV) was 250-3600 microU/L and the sensitivity 20.8 +/- 7.2 microU/L. The between-assay variability, evaluated from replicate measurements in different runs of two serum pools was 14.6 CV% for the first pool (259.1 +/- 37.8 microU/L) and 14.3 CV% for the second pool (442.0 +/- 63.1 microU/L), respectively. To evaluate the clinical usefulness of myosin as a marker of myocardial cell damage, serum myosin was measured in patients with acute myocardial infarction (AMI) (n = 9) or subarachnoid hemorrhage (n = 20). The results obtained with the myosin assay were compared with those of two other markers considered specific for myocardial necrosis (CK-MB and myoglobin). In eight patients with AMI, serum myosin was elevated 24-36 hours after the onset of chest pain and reached a maximum at 4-7 days, returning to control levels at 8-11 days. The one remaining AMI patient showed two subsequent peaks in serum CK-MB and myoglobin concentrations (thus suggesting an extension of myocardial necrosis), the myosin concentrations reaching their peak only after 9 days.(ABSTRACT TRUNCATED AT 250 WORDS)

The hemodynamic, electrocardiographic, and coronary flow responses to a psychological test were studied in 13 pigs both in the absence (group 1, n = 8) and the presence (group 2, n = 5) of a transient occlusion of the left anterior descending coronary artery. The psychological test consisted of presenting food to a fasting but restrained animal for 3 minutes. In group 1, stress increased the heart rate from 128 +/- 5 to 176 +/- 8 beats/min (mean +/- SEM) and arterial pressure from 93 +/- 4 to 112 mm Hg. Comparing the individual increase in rate-pressure product with the increase in coronary conductance during the test, a parallel response was found in only two animals, whereas a relatively lower coronary conductance was observed in the remainder, suggesting vasoconstriction. Clinical signs of ischemia or life-threatening arrhythmias were never observed in this group of animals. Each group 2 animal underwent two occlusions of the left anterior descending coronary artery, randomly performed on separate days both in the presence and the absence of the food deprivation stress. When the latter was applied in the presence of occlusion, all animals developed ventricular fibrillation in less than 2 minutes (mean, 81.4 seconds). Conversely, only one animal had ventricular fibrillation when a 3-minute occlusion was performed without exposure to stress. This occurred despite the fact that more severe ischemia (as detected by an increase in left ventricular end-diastolic pressure and decreases in dP/dt and systolic pressure) was recorded at 3 minutes of occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

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)

Patients with frequent attacks of angina at rest and/or upon minimal effort represent a subset of patients with unstable angina who are at risk for myocardial infarction and cardiac death and who require adequate intensive care. Several mechanisms, either alone or in combination, are thought to be responsible for such a condition: atherosclerotic plaque rupture, coronary hypertone, platelet aggregation, and thrombosis. In the great majority of these patients, nitrates and calcium antagonists have been shown to be very effective in reducing ischemic attacks, probably by reducing coronary smooth muscle contraction [1, 2]. To rapidly and effectively “cool down” the disease, infusion of such drugs is especially needed in patients with a high number of ischemic attacks per day [3–5]. The aim of this study was to evaluate the efficacy of i. v. nifedipine in patients admitted to the coronary care unit (CCU) because of frequent anginal attacks at rest.

We have investigated whether vasospastic anginal attacks might be associated with myocardial cell damage even when permanent ORS or ST-T changes are absent. We obtained serum time-activity curves of creatine kinase MB, of myoglobin, and of alpha hydroxybutyrate dehydrogenase in 15 patients with vasospastic angina admitted to our Coronary Care Unit (CCU). A slight but consistent rise and fall of both myoglobin and creatine kinase MB was observed in 7 patients (4 presented a definitive myocardial uptake of 99mTc pyrophosphate, and I had a faint deposition). A similar pattern was observed for myoglobin alone in 3 patients (1 presented a negative myocardial scan), while no consistent changes were found in the remaining 5 patients (2 presented a faint deposition of 99mTc pyrophosphate). No significant change of alpha hydroxybutyrate dehydrogenase was observed in any of the patients. The coherent rise and fall of the levels of myocardial cytosolic components after prolonged episodes of vasospastic angina suggests that cell damage may occur even in the absence of persistent QRS and ST-T changes.

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.

We have investigated whether vasospastic anginal attacks might be associated with myocardial cell damage even when permanent ORS or ST-T changes are absent. We obtained serum time-activity curves of creatine kinase MB, of myoglobin, and of alpha hydroxybutyrate dehydrogenase in 15 patients with vasospastic angina admitted to our Coronary Care Unit (CCU). A slight but consistent rise and fall of both myoglobin and creatine kinase MB was observed in 7 patients (4 presented a definitive myocardial uptake of 99mTc pyrophosphate, and I had a faint deposition). A similar pattern was observed for myoglobin alone in 3 patients (1 presented a negative myocardial scan), while no consistent changes were found in the remaining 5 patients (2 presented a faint deposition of 99mTc pyrophosphate). No significant change of alpha hydroxybutyrate dehydrogenase was observed in any of the patients. The coherent rise and fall of the levels of myocardial cytosolic components after prolonged episodes of vasospastic angina suggests that cell damage may occur even in the absence of persistent QRS and ST-T changes.

It is widespread convinction that emotional factors may interact with cardiovascular function and produce both acute and chronic ischemic heart disease. In spite of this fact, a systematic investigation, on a short term basis, of the role of psychological stressors in the production of acute myocardial ischemia is lacking.

Infusions of DL-carnitine are reported to improve the tolerance to atrial pacing of patients with angina pectoris. In the present study, six patients with angina of effort and triple vessel disease received two placebo and two carnitine infusions administered in a double-blind randomized fashion. Carnitine did not affect either the double product (heart rate X systolic blood pressure) at maximal pacing (ST depression: 2.3 +/- 0.2 mm, +/- SEM) or the tolerated pacing time. Intravenous carnitine, in the dose given, is of no therapeutic benefit in myocardial ischemia precipitated by tachycardia. It could be effective when free fatty acids are elevated as during catecholamine stimulation.

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)

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.

This session deals with a rather different aspect of those that have been discussed yesterday and this morning, because it is meant to explore the problems of the coronary care in the research environment for the definition of fields of possible future, concerted research.

Angiotensin-converting enzyme (ACE) inhibitors reduce mortality, the development of remodeling, left ventricular (LV) dysfunction, and ischemic events, both when administered alone as long-term treatment in patients with impaired LV function and/or heart failure (HF) and as short-term treatment, early after acute myocardial infarction (AMI) and/or HF. The few data available on the use of ACE inhibitors in the elderly after AMI are conflicting. Nothing is known about the effects of ACE inhibitors in elderly postinfarction patients with preserved LV function: these patients have a remarkable medium- to long-term mortality and HF incidence after infarction. The aim of this study is to evaluate, in patients with AMI agedor =65 years, the effects of Perindopril on the combined outcome of death, hospitalization for HF, and heart remodeling, considered to be aor =8% increase in LV end-diastolic volume (LVEDV). Secondary objectives include the same factors listed in the primary end points but considered separately. In addition, safety of the drug, ventricular remodeling, and adaptation are being evaluated. A total of 1100 patients with AMI (first episode or reinfarction), agedor =65 years, and preserved or only moderately depressed LV (LV ejection fractionor =40%), are to be enrolled and randomly assigned to treatment (8 mg for 12 months of Perindopril or placebo, in double-blind conditions). Clinical assessment is performed at fixed times, and periodic evaluations of (1) ventricular shape, dimensions, and function by quantitative 2-D echocardiography, and (2) heart rate variability and arrhythmias by ambulatory electrocardiographic monitoring are anticipated. The results and conclusions will be available by 2002 year.