[Thrombocytopenia induced by heparin: report of a clinical case]. / Trombocitopenia indotta da eparina: descrizione di un caso clinico.

Heparin-induced thrombocytopenia (HIT) is a possible complication of heparin administration consequent to an immunological reaction. It usually resolves without clinical sequelae with discontinuation of the drug. However, sometimes it causes severe platelet activation with thrombosis. The therapeutic strategy for HIT has only recently been established. In particular, in view of a possible worsening of the thrombotic status, some concerns have been raised about the early use of oral anticoagulation. We report a case of a 57-year-old woman in whom severe HIT occurring after a few days of heparin treatment for pulmonary embolism was treated using low doses of warfarin. The recent literature on HIT is reviewed and the lack, at the present, of valid pharmacological alternatives in Italy is emphasized.

Hyperkinetic ventricular arrhythmias in very elderly people with and without cardiac disease. Correlation with left ventricular echocardiographic parameters.

BACKGROUND: Morphological and functional changes induced by aging can hamper a clear distinction between pathological or paraphysiological phenomena in very old people. The incidence of hyperkinetic ventricular arrhythmias, for example, progressively increases in the elderly, even in the absence of overt cardiac disease. METHODS: One-hundred fifty-two clinically stable patients older than 80 years, submitted within 15 days to clinical evaluation, 24-hour continuous ambulatory ECG monitoring and echo Doppler examination, in the absence of antiarrhythmic treatment, were retrospectively selected in order to evaluate the incidence of ventricular arrhythmias, in patients with and without significant heart disease. The further aim of the study was to correlate the number of arrhythmias with left ventricular morphological and functional parameters, echocardiographically assessed. From the initial population, 80 patients (41 males, age 83 +/- 3 years) had significant heart disease (ischemic, hypertensive or valvular): Group I. Seventy-two patients (30 males, age 83 +/- 3 years) had no clinical or instrumental signs of heart disease: Group II. RESULTS: Considering echocardiographic data, Group I patients had a significantly higher left ventricular end-diastolic diameter (52 +/- 6 mm vs 47 +/- 4 mm, p < 0.01), lower ejection fraction (57 +/- 10% vs 64 +/- 6%, p < 0.01) and higher mass (275 +/- 84 g vs 208 +/- 46 g, p < 0.01), when compared with Group II. From ECG monitoring data, significant differences between the two groups were recorded in the incidence of premature ventricular beats per hour (79 +/- 163 vs 15 +/- 34, Group I vs Group II, p < 0.01) and presence of complex phenomena (couplets, triplets and runs: 51% vs 22%, p < 0.01). In old patients with documented cardiac disease a significant correlation was present between premature ventricular beats incidence and left ventricular end diastolic diameter (r = 0.39, p < 0.05) and left ventricular ejection fraction (r = 0.40, p < 0.05), while in patients without heart disease, no significant correlation was found between incidence of premature ventricular beats and echocardiographic morpho-functional parameters. CONCLUSIONS: In conclusion, hyperkinetic ventricular arrhythmias are globally frequent in old persons of very advanced age (more than 80 years), but, also in this subset, a significant distinction in terms of incidence and severity of arrhythmias is present between subjects with and without cardiac disease. A significant correlation between incidence of premature beats and non-invasive morpho-functional left ventricular parameters is present only for patients with overt heart disease.

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)

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.

[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.

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.

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.

Microalbuminuria and casual and ambulatory blood pressure monitoring in normotensives and in patients with borderline and mild essential hypertension.

Several reports suggest that urinary albumin excretion may be elevated in patients with essential hypertension and that this index may be a good predictor for cardiovascular complications. The aim of this study was to compare 24-hour urinary albumin excretion in a group of normotensives, borderline, and untreated mild hypertertensives and to assess, in a subgroup of them, the possible relations between microalbuminuria and arterial blood pressure. Fifteen normotensives, 16 borderline, and 19 mild hypertensive patients were studied. Slightly but significantly higher values of microalbuminuria were observed in the mild hypertensives compared to the other two groups. In 21 borderline and mild hypertensive patients 24-hour microalbuminuria was related to casual blood pressure and noninvasive ambulatory blood pressure monitoring. A significant correlation was found between microalbuminuria and average day-time diastolic blood pressure. Our data suggest that albumin excretion is slightly increased in mild arterial essential hypertension; the direct association between microalbuminuria and arterial diastolic blood pressure during daily activities seems to confirm a pathophysiological link between transcapillary protein escape and arterial blood pressure that warrants further studies.

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)

Long-term reproducibility and evaluation of seasonal influences on blood pressure monitoring.

The aim of this study was to evaluate the long-term reproducibility and the possible seasonal influences on casual blood pressure and ambulatory blood pressure monitoring in patients with borderline or mild arterial hypertension. Two sets of measurements were performed at 6-month intervals, one set in the warm and one in the cold season, using the same protocol, consisting of measurements of casual and ambulatory blood pressures, together with the recording of outdoor temperatures. Casual blood pressure was measured by an automatic recorder and 24-h ambulatory blood pressure monitoring was performed by a non-invasive device. For the selected intervals, the reproducibility of most pressure measurements was low; in addition, casual diastolic pressure and 24-h systolic and diastolic pressures were significantly higher in the cold than in the warm season. Taken together, these findings confirm and extend the results obtained in several large-scale studies and support the importance of taking environmental temperature into account, not only in epidemiological studies but also in small-scale studies and probably even in the individual patients, especially when using integrated evaluations by ambulatory monitoring.

Relationship between pain sensitivity, cardiovascular reactivity to cold pressor test and indexes of activity of the adrenergic and opioid system.

An association between increased blood pressure levels and hypoalgesia has been reported in the experimental animal and in man. The relation between pain perception and cardiovascular function is however still obscure. In order to gain some insight into this aspect, normotensive subjects with low and high tolerance to pain, as assessed by tooth pulp stimulation, were compared for blood pressure and heart rate during cold pressor test, 24 hr urinary catecholamines, supine and upright PRA and plasma beta-endorphin levels. No significant difference was observed between the two groups for casual blood pressure, heart rate and PRA. Compared to subjects with low tolerance to pain, those with high tolerance to pain were significantly older and had: 1) significantly higher levels of diastolic blood pressure and of beta endorphin levels during cold pressor test; 2) significantly higher beta-endorphin levels after cold pressor test; 3) a significantly higher excretion of noradrenaline (but not of adrenaline and dopamine).

Cardiovascular reactivity to physical and psychologic stress during long-term treatment with nitrendipine in essential hypertension.

Nitrendipine is a second-generation dihydropyridine calcium antagonist selective for hypertension. The aim of this study was to assess whether, in addition to reduce resting blood pressure, nitrendipine also affects the cardiovascular reactivity to physical and psychologic stress. Ten essential hypertensive patients, out of treatment for at least 2 weeks, underwent a symptom-limited dynamic maximal exercise and a mental arithmetic stress test (MAT) after placebo (1 week) and 1 and 5 weeks of active treatment with nitrendipine (20 mg q.i.d.). To evaluate the cardiovascular response to exercise and its changes during treatment, the slope of the regression line (if statistically significant) of the blood pressure, heart rate, and rate-pressure product (RPP) values against workload were considered, together with exercise capacity, blood pressure, and pressure-rate product at the peak of maximal exercise. During mental stress, indexes of stroke volume (SVI), cardiac output (COI), and peripheral resistance (TPRI) were obtained by Doppler transcutaneous aortovelography (TAV). Resting systolic and diastolic BP were significantly reduced during treatment. The average length of exercise was 7.3, 7.64, and 8.0 min after, respectively, placebo, 1, and 5 weeks of treatment. Peak systolic and diastolic BP, peak RPP, and RPP slope were consistently decreased after treatment, significantly for peak DBP and RPP. During mental arithmetics, a significant increase of BP and HR and a decrease of SVI were observed on placebo; both BP and SVI responses disappeared after 5 weeks on nitrendipine, whereas the HR increase was unchanged. Peak values of COI and TPRI during MAT were significantly increased and decreased, respectively, after nitrendipine, whereas basal values showed similar changes, but not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Medium-term reproducibility of stress tests in borderline arterial hypertension.

Stress tests are commonly used for an evaluation of blood pressure reactivity, but few data exist in the literature about interindividual variability and intraindividual medium-term reproducibility of blood pressure responses to these tests in borderline hypertension. To this aim we have studied 20 borderline hypertensive patients (age range, 33-59, mean 45). Our data suggest that borderline hypertensive patients cannot be considered a homogeneous group with regard to blood pressure reactivity because they tend to have widely different blood pressure responses to various stress tests. For each test (except for orthostatic stimulation), a fairly good intraindividual reproducibility was found. Considering the poor correlations existing between blood pressure responses to tests for each patient, one test may not be sufficient to characterize blood pressure reactivity to stress in borderline hypertension.