[Stress imaging in coronary artery disease: state of the art]. / Stress imaging nella cardiopatia ischemica: stato dell'arte.

To date, several diagnostic tools allow an accurate non-invasive evaluation of coronary artery disease; this is due to the great progress in echocardiographic and nuclear imaging techniques in the last 10 years. The large availability of different stress imaging techniques allows to choose the most appropriate technique for each patient according to the clinical characteristics. This paper presents the state of the art of echocardiographic and nuclear stress imaging for the diagnosis of coronary artery disease and for the prognostic stratification of infarcted patients. Advantages and limits of the different techniques are described rather than putting in competition echo and nuclear cardiology as has often been done in the past. Cardiologists should select among the various techniques on the basis of clinical characteristics of single patients, center's experience and an objective evaluation of economical aspects.

[Holter-detected myocardial ischemia. Impact for prognosis and decision making after acute myocardial infarction]. / Ischemia all'Holter. Impatto prognostico e decisionale nel post infarto.

BACKGROUND: Aim of the study was to evaluate the prognostic and decision making value of Holter detected myocardial ischemia after acute myocardial infarction in comparison with clinically detected postinfarction angina and exercise test. METHODS: To this aim the patients consecutively admitted to our coronary care unit with acute myocardial infarction during one year were retrospectively evaluated. One hundred and eighty-nine patients (age 70+/-11 years, 137 male and 51 female) had a 24 hour Holter monitoring. One-year follow up of these patients was obtained. RESULTS: Myocardial ischemia was detected by Holter monitoring in 21 patients (11%), 4 with and 17 without angina. Symptom limited exercise test was obtained before discharge in 116 patients (62%): 45% were positive, 42% non-diagnostic and 13 negative for myocardial ischemia. Post infarction angina was present in 15 patients (9%). Patients with Holter detected myocardial ischemia were older (73+/-10 vs 66+/-11 years, p<0.05) and had higher prevalence of both angina and positive exercise test (p<0.01). One-year follow up was obtained in 186 patients. Holter detected myocardial ischemia positive predictive value for death or reinfarction was 15%, negative predictive value was 90%, similar to the absence of angina (90%) and the absence of positive exercise test (93%). Angina and exercise test identified 62% of patients with Holter detected myocardial ischemia. Residual myocardial ischemia was exclusively observed by Holter monitoring in 4% of the population, particularly in 1 patients with and 7 without exercise test. CONCLUSIONS: The additive contribution of Holter detected myocardial ischemia in the prognosis and decision making of post infarction patients is rather scanty.

Diastolic function in the different patterns of left ventricular adaptation to essential hypertension.

Recent reports have shown that four distinct left ventricular anatomical patterns, with different hypertension severity and hemodynamic features, are associated with sustained arterial hypertension (normal anatomy, concentric remodeling, concentric hypertrophy and eccentric hypertrophy). The aim of this study was to evaluate left ventricular diastolic function in these different left ventricular anatomic patterns. To achieve this aim, 94 borderline-to-severe essential hypertensive patients (60 never treated before, 34 off treatment for at least 3 weeks before the study) underwent an echo-Doppler study; left ventricular thickness, dimension and mass index were obtained. Early (E) and late (A) transmitral flow velocity, their ratio (A/E) and the early filling fraction (EFF) were obtained by pulsed-wave Doppler and used as left ventricular diastolic function indexes. Differences between groups were evaluated by one-way ANOVA followed by Scheffe F-test. A normal left ventricular anatomy was found in 41 (44%), concentric remodeling in 17 (18%), concentric hypertrophy in 21 (22%) and eccentric hypertrophy in 15 (16%) patients. Early filling fraction and A/E ratio which resulted were significantly different for the groups (P < 0.001 and P < 0.002, respectively). As compared with the group with normal left ventricle, patients with concentric hypertrophy had significantly EFF and those with eccentric hypertrophy had significantly lower EFF and higher A/E ratio. Our results thus confirm the presence of distinct anatomical left ventricular adaptation patterns in arterial hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac morphology and function in arterial hypertension. The effects of a new multifactorial hypotensive agent: urapidil.

It has been recognized as increasingly important to determine whether antihypertensive agents, while satisfactorily lowering the blood pressure, at the same time adversely or positively affect the cardiac hemodynamic profile. On theoretical grounds, one would expect that an ideal hypotensive drug should decrease blood pressure by decreasing total peripheral resistances, without affecting cardiac output, and should normalize left ventricular hypertrophy without deteriorating systolic or diastolic left ventricular function. We here briefly review the effects of urapidil on these variables in patients under chronic treatment investigated in a series of studies employing echocardiography. The results of the studies are in fair agreement and indicate a blood pressure decrease already after one month of treatment, due to a decrease of peripheral resistances, without changes in heart rate. A clear trend towards a reduction of cardiac hypertrophy during the treatment is suggested by the significant decrements of the indices measured. One study also suggests that right ventricular wall thickness may be reduced. Left ventricular dimensions remained unchanged in all except one study. Systolic and diastolic function indices were also unchanged during the first 6 months of treatment and, in one study, improvement was found after 12 months of treatment. Taken together these results suggest that urapidil lowers blood pressure favorably, affecting cardiac morphology and function.

Echo Doppler diastolic function and exercise tolerance.

OBJECTIVE: To investigate the possible association between Doppler left ventricular filling pattern and exercise capacity in a group of normotensives to severe hypertensive patients. BACKGROUND: Invasive left ventricular filling indexes evaluated at rest are reported to be related to exercise capacity in heart failure. Whether exercise capacity is limited by abnormalities of left ventricular filling also in other less severe conditions is however unclear. METHODS: Fifty-one subjects with normal to severely elevated blood pressure underwent a standard exercise test on cycle ergometer, negative for myocardial ischemia, and a complete echo Doppler evaluation showing a basal systolic function within normal limits. RESULTS: Basal systolic function indexes were not significantly related to exercise duration. On the contrary, exercise duration was highly significantly correlated to the relative atrial contribution to left ventricular filling (0.001 < P < 0.05), in both the overall group and the two subgroups in whom exercise was interrupted because of fatigue (n = 30) or because of attaining target heart rate (n = 21). Significant correlations were also observed between exercise time and resting blood pressure, whereas no association with resting heart rate, age and body surface area was found. Exercise time also correlated to left ventricular mass and mass index but not to left ventricular volume. Multiple regression analysis showed that exercise tolerance was significantly related to diastolic blood pressure and left ventricular filling. Echo Doppler indexes of left ventricular filling are associated with exercise duration; left ventricular diastole could thus influence effort tolerance, not only in patients with cardiac insufficiency, but also in subjects with normal to elevated blood pressure levels and normal systolic function at rest.

Normal ultrasonic myocardial reflectivity in hypertensive patients. A tissue characterization study.

Ultrasonic backscatter of myocardial walls is directly related to the morphometrically evaluated collagen content in humans. The integrated backscatter is also increased in hypertrophic cardiomyopathy, whereas it gives normal values in the physiological hypertrophy of elite athletes. We assessed the quantitatively evaluated myocardial reflectivity in 46 mild to moderate, clinically uncomplicated essential hypertensive patients, with echocardiographically assessed normal regional and global left ventricular function, and 22 age- and sex-matched normotensive control subjects. With an echo prototype implemented in our institute, we performed an on-line radiofrequency analysis to obtain quantitative operator-independent measurements of the integrated backscatter signal of the ventricular septum and posterior wall. The integrated values of the radiofrequency signal of myocardial walls were normalized for those of the pericardial interface and expressed as a percent (integrated backscatter index). Hypertensive patients and control subjects differed in mean blood pressure (119 +/- 11 versus 95 +/- 5 mm Hg, p < 0.001) and left ventricular mass index (134 +/- 31 versus 105 +/- 21 g/m2, p < 0.001). However, integrated backscatter index overlapped for both the septum (28 +/- 17% versus 25 +/- 6%, p = NS) and the posterior wall (13 +/- 7% versus 13 +/- 4%, p = NS). In the hypertensive group, there was no detectable correlation between septal integrated backscatter index and either septal thickness (r = -0.26, p = NS) or mean arterial pressure (r = -0.14, p = NS). Hypertensive patients showed a normal pattern of quantitatively assessed ultrasonic backscatter, even in the presence of left ventricular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

[Relationship of Doppler indexes of left ventricular filling and exertion tolerance]. / Relazioni tra indici Doppler di riempimento ventricolare sinistro e tolleranza allo sforzo.

The aim of this study was to evaluate if Doppler indexes of left ventricular filling are related to exercise capacity. Since a correlation between left ventricular filling pattern and causal blood pressure has been recently reported along a wide range of pressure values, a group of subjects with blood pressure ranging from normal to severely elevated values was studied. Twenty-four subjects (11 normotensives, 13 mild to severe hypertensive patients) underwent an echo-Doppler study and a maximal multistage cycloergometric exercise test. Since the cycloergometric test was limited by fatigue or dyspnea in all subjects, exercise duration was used as an effort tolerance index. Echocardiographic indexes of systolic function resulted normal in all subjects. Significant relationships with exercise duration were found for several indexes of left ventricular filling (A peak: r = -.743, p < .0001; A/E ratio: r = -.606, p < .005; early filling fraction: r = .639, p < .001). Exercise time was also significantly related to casual blood pressure, both systolic and diastolic. The relationships between transmitral blood flow and exercise capacity seem to indicate that an impairment of ventricular relaxation (as indicated by the progressive increase of atrial contribution) is associated with a decreased exercise tolerance, possibly because a progressively lower activation of Frank-Starling mechanism. Diastolic function thus seems to be able to affect exercise tolerance even in subjects with normal systolic function and blood pressure ranging from normal to severely elevated values.

Electrocardiographic signs of atrial overload in hypertensive patients: indexes of abnormality of atrial morphology or function?

Left atrial electrocardiographic (ECG) abnormalities have been reported as common findings in hypertension; however, their relationships with atrial anatomy are still uncertain. In addition, in arterial hypertension several studies demonstrated an abnormal left ventricular filling. The aim of this study was to investigate the relationships of the ECG signs of left atrial abnormality to atrial anatomy and left ventricular filling as evaluated by pulsed-wave (PW) Doppler in a group of patients with uncomplicated essential hypertension. To this end, 53 untreated essential hypertensive patients (age 44 +/- 8 years; blood pressure 160.5 +/- 21.5/104.7 +/- 13.5 mm Hg) underwent a complete 12-lead ECG and a PW Doppler study of the transmitral flow velocities. The ECG criteria of left atrial abnormality were: P wave wider than 0.12 (or 0.10) second or higher than 0.25 mV in lead II; P wave/PR segment ratio (Macruz index) greater than 1.6 in lead II; and P wave terminal forces in lead V1 equal to or more negative than 0.04. Echocardiographic measurements were made according to American Society of Echocardiography (ASE) convention. Doppler parameters of left ventricular filling were measured as E and A peak velocity, A/E ratio, and the ratio between the velocity-time integral under the E peak and that of the whole diastolic flow, which represents the rapid filling fraction (RFF). At least one ECG sign of atrial abnormality was present in 34 patients (64%); the Macruz index gave the most common ECG index of atrial abnormality (31 patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Casual, ambulatory and stress blood pressure: relationships with left ventricular mass and filling.

In arterial hypertension, casual blood pressure seems to be weakly related to the level of cardiac involvement. The aim of the present study was to assess if blood pressure during ambulatory monitoring, and during different stress tests, is a stronger predictor of anatomical and functional changes observed in hypertensive heart disease. To this aim, 29 untreated patients with borderline-to-moderate essential hypertension underwent an echo-Doppler evaluation to determine left ventricular thickness and mass. From transmitral flow, the ratio between late and early filling velocities (A/E ratio) was used to assess left ventricular diastolic behaviour. On the same day that ultrasonic study was carried out, we also measured a set of casual blood pressures; conducted a mental arithmetic test (standardized series of mental subtractions); a handgrip test (30% of maximum voluntary contraction for 3 minutes); and performed noninvasive ambulatory monitoring of blood pressure (Spacelabs 5200). Significant relationships were observed between left ventricular mass and both night-time systolic blood pressure (r = 0.46, P less than 0.02) and peak systolic blood pressure during mental stress (r = 0.39, P less than 0.05). The A/E ratio was significantly associated with casual systolic and diastolic blood pressure (r = 0.45, P less than 0.02; r = 0.38, P less than 0.05, respectively); day-time diastolic blood pressure (r = 0.47, P less than 0.02); night-time systolic and diastolic blood pressure (r = 0.44, P less than 0.05; r = 0.42, P less than 0.05 respectively); and peak systolic blood pressure during the mental arithmetic test (r = 0.44, P less than 0.05). Our results seem to confirm the presence of a relationship between causal blood pressure and left ventricular filling. Moreover, the transmitral flow seems to be dependent on both mean levels of blood pressure on ambulatory monitoring and systolic blood pressure during mental stress. As concerns left ventricular mass, the correlations observed support the weakness of the links between blood pressure and left ventricular anatomy.

Left ventricular filling: relationship with arterial blood pressure, left ventricular mass, age, heart rate and body build.

The relationships of age, heart rate, body build and, in particular, of arterial blood pressure and left ventricular mass to several Doppler indexes of diastolic function were evaluated in a series of 80 subjects with a wide range of blood pressure levels (106-217/68-144 mmHg). Body build and age results were inversely correlated to the indexes, reflecting the early contribution to left ventricular filling, whereas the increase in heart rate was associated with an increase in late diastolic contribution. Strong correlations (in most instances, P less than 0.0001) were observed with arterial blood pressure and left ventricular mass: the increase of these parameters was associated with a decrease of early transmitral peak velocity (E peak) and of early filling fraction, with an increase of late diastolic transmitral peak velocity (A peak) and of A:E ratio and, finally, with an increase of both deceleration time of E peak and acceleration time to A peak. Blood pressure or left ventricular mass were also confirmed as strong predictors of nearly all the Doppler-derived diastolic indexes by stepwise multiple regression analysis. When the subjects were subdivided into quintiles according to diastolic blood pressure and the average values of the five subgroups were compared, age, heart rate and body build results were similar in the quintiles while diastolic blood pressure increased stepwise by 10 mmHg. Analysis of variance showed significant differences for all the indexes of left ventricular filling except deceleration time of and acceleration time to E peak (P less than 0.05 to P less than 0.0001) and almost all the echo-Doppler indexes showed a linear trend with diastolic blood pressure and left ventricular mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Echo-Doppler assessment of left ventricular filling in borderline hypertension.

The aim of this study was to evaluate left ventricular anatomy and diastolic function in borderline essential hypertension. To this aim, 16 borderline hypertensive patients underwent echocardiographic and pulsed-wave Doppler evaluation. As control groups, 20 normotensive controls and 20 patients with established hypertension were evaluated by the same procedure. By the Doppler assessment of transmitral blood flow, the following indices of left ventricular diastolic function were obtained: early (E) and late (A) peak flow velocity, late to early velocity ratio (A/E), early filling fraction (EFF) and acceleration and deceleration times of early and late flow peaks. Borderline hypertensives had an interventricular septum and posterior wall thickness significantly higher than normotensives and lower than established hypertensives. As regards the diastolic indexes, borderline hypertensive patients had significantly higher A peaks (P less than .02) and A/E ratios (P = .05) and lower EFF (P less than .02) as compared to normotensive controls. No significant differences were on the other hand observed with established hypertensive patients. This resultant diastolic pattern was independent of age, as indicated by the analysis of age-matched subgroups. The presence of diastolic function changes in borderline hypertension confirms the early appearance of this kind of abnormality in hypertensive heart disease. On the other hand, the finding of increased left ventricular wall thickness in borderline hypertensives does not allow us to conclude that, as suggested by other authors, diastolic function changes in the early stage of hypertension are independent on anatomical modifications.(ABSTRACT TRUNCATED AT 250 WORDS)

Reduced cardiovascular efficiency and increased reactivity during exercise in borderline and established hypertension.

In this study, exercise capacity was evaluated in patients with borderline and established, uncomplicated, essential hypertension as compared to normal subjects. To this aim, the response of blood pressure, heart rate and cardiac work to a multi-stage exercise test was investigated by analyzing the results of linear regression fitting of cardiovascular parameters (ie, heart rate, systolic blood pressure and rate-pressure product (RPP)) versus time of exercise. Compared to normal patients, both essential and borderline hypertensive patients had a shorter average duration of exercise test (ie, a decreased exercise capacity), always negative for transient myocardial ischemia. This was in spite of a mild increment of maximal RPP (+19% and +10% v normal patients, respectively). Reduction of exercise duration in borderline and established hypertensive patients was related to the higher RPP at rest (+26% and +56% related to normal patients, respectively) and to the steeper slopes (rates of increment) of heart rate systolic pressure and RPP during exercise. Interestingly, in the overall population of normal and hypertensive subjects, the slopes of heart rate and RPP were directly correlated with basal blood pressure. In conclusion, these data indicate a decreased exercise tolerance in both established and borderline hypertensive patients without documented myocardial ischemia. This abnormality, which appears to be due to a disproportional increment during exercise not only of systolic pressure but also of heart rate, could reflect abnormalities in the autonomic control of heart function.

Comparison between endogenous digoxin-like immunoreactivity and 86Rb uptake by erythrocytes in extracts of human plasma.

1. To investigate endogenous cardiac glycoside-like compounds in plasma and their ability to inhibit the sodium pump, digoxin-like immunoreactivity [digoxin-like immunoreactive substance(s), DLIS] and 86Rb uptake by erythrocytes were measured in plasma extracts from normal adults, hypertensive adults and neonates. 2. DLIS levels in neonate plasma extracts were significantly higher than those found for normotensive or hypertensive adults. No difference was observed between normotensive and hypertensive subjects. DLIS was significantly increased when boiled plasma was extracted. 3. Extracts of boiled neonate and adult plasma inhibited 86Rb uptake. Instead, when boiling was omitted, no detectable inhibition was found in extracts of plasma from normotensive or hypertensive adult subjects. When present, the inhibition resulted from a depression of the ouabain-sensitive (sodium-pump-mediated) component, and, for the boiled neonate plasma only, also of the ouabain-resistant component. When the data from the different groups were pooled, a statistically significant inverse relationship between DLIS and erythrocyte 86Rb uptake was observed. Furthermore, in a subgroup of samples in which determinations were made before and after boiling in the same samples, an inverse correlation was found between changes in DLIS and changes in ouabain-sensitive (but not ouabain-resistant) 86Rb uptake. 4. Plasma extracts incubated with albumin at a physiological concentration significantly decreased (by approximately 20%) the inhibition of 86Rb uptake observed. 5. These findings support the existence of one or more endogenous compounds which both bind to antidigoxin antibodies and inhibit transmembrane cation transport. Part of this inhibition may, however, not involve the sodium pump. Furthermore, this chemically unidentified substance(s) may be bound to plasma proteins which partly reduce its action in vivo.

Seasonal influences on blood pressure in high normal to mild hypertensive range.

To investigate the seasonal influences on various arterial blood pressure measurements, 22 subjects in the high normal to mild hypertensive range were examined twice following the same protocol. In one group (13 subjects), measurements were first done in warm conditions and repeated 5-7 months later in cold conditions; in the second group (nine subjects) a reverse sequence was followed. Blood pressure was measured under casual conditions during a hand grip exercise test, mental arithmetic test, and submaximal multistage bicycle exercise test; during the following 24 hours, blood pressure was measured serially with a noninvasive ambulatory blood pressure recorder. Daily outdoor maximum and indoor laboratory temperatures were also obtained. In the cold season, significantly higher values (on the average by 5-10 mm Hg, p less than 0.01) were obtained in both groups for mean diastolic daytime blood pressure. For other measurements, a trend toward higher values in the cold season was observed in both groups, although statistical significance was not obtained in all instances. For nighttime measurements, irrespective of the seasonal sequence, lower values were observed in the second session. Significant correlations were found between the differences in the average daytime ambulatory blood pressures and the corresponding changes of daily maximum outdoor temperatures after 5-7 months. These observations indicate that arterial blood pressure may be strongly influenced by environmental temperature. This phenomenon should be taken into account both in the evaluation of the individual hypertensive patients and in the design and analysis of studies on arterial hypertension, especially when ambulatory blood pressure techniques are employed.

Different determinants of left ventricular filling in normotensive subjects and essential hypertensive patients.

The aim of the study was to evaluate the relationships between left ventricular (LV) filling and age, heart rate (HR), blood pressure (BP), and LV mass in three groups of subjects with different casual blood pressure. Twenty normotensive subjects (NT: age 39.2 +/- 7.2; BP 121.6 +/- 11.3/77.7 +/- 7.5 mm Hg), 16 borderline hypertensives (BH: age 38.6 +/- 9.2; BP 138.2 +/- 11.6/91.7 +/- 9.4 mm Hg), and 20 essential hypertensives (EH: age 44.5 +/- 8.3; BP 165.7 +/- 14.8/107.6 +/- 11.4 mm Hg) underwent 2D Echo evaluation and PW Doppler measurements of transmitral blood flow velocity. In NT, the Doppler indexes of LV filling showed significant correlations only with age and heart rate (age v E peak: r = .68 P less than .001; v A peak: r = .45, P less than .05; v A/E: r = .78, P less than .001. Heart rate v A peak: r = .78, P less than .001, v A/E: r = .74, P less than .001, respectively). Similar but weaker relationships were observed in BH. On the contrary, EH showed no significant correlations with age or heart rate, but with both systolic blood pressure (SBP), diastolic blood pressure (DBP), and LV mass (SBP v A peak: r = .49, P less than .05; v A/E: r = .68, P less than .001; DBP v E peak: r = 44, P less than .05; v A/E: r = .58, P less than .01. Left ventricular mass v E peak: r = .45, P less than .05; v A/E: r = .51, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular mass in borderline hypertension, assessed by echocardiography. Relationships with resting and stress blood pressure.

The relationship between clinical measurement of blood pressure (BP) and left ventricular hypertrophy in arterial hypertension appears to be weak in most studies. On the contrary, stronger correlations with target organ damage in general, and left ventricular hypertrophy in particular, have been reported for blood pressure measurements obtained by ambulatory monitoring; this finding may indicate a possible role for blood pressure response to naturally occurring stresses in determining left ventricular hypertrophy. Aim of this study was to investigate, in 18 patients with borderline arterial hypertension, the relationships between echocardiographically assessed left ventricular mass and, respectively, casual BP and BP responses to some standardized stress tests. Only three patients had a diastolic wall thickness of the interventricular septum and of the posterior wall greater than or equal to 1.2 cm and none had a pathologically increased left ventricular mass index. The following statistically significant correlations were found: casual diastolic BP vs. left ventricular mass index (r = 0.53, p less than 0.02), systolic BP response to bicycle exercise test vs. left ventricular mass index (r = 0.55, p less than 0.05). Multiple regression analysis showed that almost fifty percent of the variability of left ventricular mass index could be predicted by these two BP measurements. These findings suggest that besides the chronically increased afterload, also the transient hypertensive responses to naturally occurring physical stresses may have a role in determining the extent of cardiac structural changes in borderline hypertensive patients.(ABSTRACT TRUNCATED AT 250 WORDS)