Alessandra Villani

Lack of placebo effect on ambulatory blood pressure.

Several studies have reported that, at variance with clinic blood pressure, ambulatory blood pressure is not reduced by treatment with placebo. However, this evidence has usually been obtained in small groups of subjects and no data are available from a larger sample of patients. To address this issue we have analyzed data from 116 outpatients involved in placebo-controlled studies on antihypertensive treatment. The patients were studied before and at the end of a 6- to 8-week period of placebo. In all patients, blood pressure was measured by sphygmomanometry and over the 24 h by automatic ambulatory monitoring. Administration of placebo was accompanied by a significant reduction in systolic and diastolic clinic blood pressure (-5.3 +/- 1.1 and -4.4 +/- 0.6 mm Hg, respectively; P < .01), but not in 24-h, daytime and nighttime blood pressure. Hourly systolic and diastolic blood pressure profiles were virtually superimposable in the two different periods, except for the first 4 h, in which systolic blood pressure was slightly but significantly lower during than before placebo (149.5 +/- 1.2 v 146.4 +/- 1.2 mm Hg; P < .05). These results provide a large database indicating that 24-h average blood pressure is not reduced by placebo, thus it is not necessary to include a placebo control group in antihypertensive drug studies in which ambulatory blood pressure monitoring is employed. A small placebo effect occurs, however, in the first hours of ambulatory monitoring. This may lead to a slight overestimation of the peak blood pressure effect of a drug and an underestimation of its trough-to-peak ratio if placebo correction of the data is not made or if the first part of ambulatory blood pressure monitoring is not excluded from data analysis.

Transthoracic bioimpedance and brain natriuretic peptide levels accurately indicate additional diastolic dysfunction in patients with chronic advanced systolic heart failure

Diastolic dysfunction in patients with heart failure has prognostic relevance, possibly because of its relationship with worsening haemodynamic status. In the quest for simpler indexes of haemodynamic status in patients, brain natriuretic peptide (BNP) levels have been proposed as a surrogate of diastolic function. To date, the value of combining BNP levels with non‐invasive haemodynamic monitoring by transthoracic electric bioimpedance (TEB) for the prediction of diastolic function has not been evaluated.

Blood pressure reduction and end-organ damage in hypertension

Value of ambulatory blood pressure monitoring: Studies that have used ambulatory blood pressure monitoring techniques have shown that the average 24-h or daytime blood pressure values are more closely related to the end-organ damage associated with hypertension than are isolated office readings. Importance of blood pressure variability in prognosis: More recently, blood pressure variability, measured as the overall 24-h blood pressure standard deviation, has been shown to have a significant relationship to end-organ damage in hypertensive patients. The potential clinical relevance of blood pressure variability has been strengthened in a recent prospective study. The possible prognostic value of blood pressure variability has practical implications for antihypertensive treatment; it may mean, for example, that the optimal antihypertensive drug should reduce not only the mean 24-h values but also the degree of fluctuation in blood pressure. This is more likely to occur with long-acting drugs, which induce a more balanced reduction in blood pressure throughout the 24 h. Use of the trough: peak ratio: A proposed measure of a balanced 24-h blood pressure effect is the trough: peak ratio of the blood pressure fall. This ratio can be obtained by clinic blood pressure measurements but ambulatory blood pressure monitoring offers some distinct advantages. One of these advantages is that by revealing the possibility of an excessive fall in blood pressure at the time of the peak effect or an uncontrolled rise at the trough, ambulatory monitoring can also reveal the possible impact of pharmacological treatment on 24-h blood pressure variability.

Reproducibility of beat-by-beat blood pressure and heart rate variability

Received 27 August 2001 Accepted 09 September 200

Changes in 24 Hour Blood Pressure and in Cardiac and Vascular Structure in Normotensive Subjects with Parental Hypertension

Subjects with family history of hypertension represent a suitable model to investigate the mechanisms responsible for early cardiovascular structural and functional changes occurring in essential hypertension. In our study we have addressed the factors involved in determining the mild elevation in office blood pressure frequently observed in normotensive subjects with hypertensive parents. In 15 normotensive subjects with both parents hypertensive (FH++) and in 15 normotensive subjects with one parent hypertensive (FH(+)-) we found no evidence of a hyperreactivity to stress as compared to the responses of 15 normotensive subjects with no parental hypertension (FH--). On the contrary FH++ subjects were characterized by a significant although mild increase in their blood pressure values recorded either at rest and in ambulatory conditions over the 24 hours, including night sleep. FH++ and FH(+)- subjects also showed a greater left ventricular mass thickness and a greater minimal forearm vascular resistance than FH-- subjects. Thus, the elevation in blood pressure found in the pre-hypertensive stage in subjects with positive family history for hypertension does not reflect a hyperreactivity to the stress associated with physicians visit but indicates an early and persistent blood pressure elevation. This blood pressure elevation is accompanied by early cardiovascular structural changes which may indicate that these subjects are exposed to a higher risk even before developing overt hypertension.

Acute effects of levosimendan on mitral regurgitation and diastolic function in patients with advanced chronic heart failure

Background We analyzed the inodilator properties of levosimendan in patients with chronic heart failure and severe functional mitral regurgitation. Methods We studied 20 patients under optimal treatment and in stable clinical condition (New York Heart Association 3.19 ± 0.66; 70 ± 7 years). Levosimendan was infused as a bolus (12 μg/kg in 10 min) followed by a 24-h infusion (0.1–0.2 μg/kg per min). Before and after infusion, Doppler echocardiography, brain natriuretic peptide determination and noninvasive hemodynamic monitoring with bioimpedance cardiography were performed. Results Levosimendan improved left ventricular ejection fraction (ejection fraction 31 ± 4 from 27 ± 4, P < 0.05), decreased brain natriuretic peptide (333 ± 139 from 629 ± 63 pg/ml, P < 0.01), reduced mitral valve effective regurgitant orifice area to 27 ± 5 from 36 ± 7 mm2 (P < 0.01) and the velocity of displacement of mitral annulus [ratio between E and E′ waves on Doppler and tissue Doppler (E/E′) from 22.7 ± 1.6 to 13.1 ± 0.6, P < 0.01]. Noninvasive hemodynamic monitoring showed increased acceleration index (a marker of inotropism), and reduced peripheral resistances and thoracic fluid content (P < 0.01). After 4 weeks of washout, some of these effects were still evident. Conclusion In patients with chronic heart failure and functional mitral regurgitation, levosimendan acutely improved systolic and diastolic function, reduced mitral regurgitation and modulated neurohormonal activation, with a tendency for these changes to persist over a short-term follow-up.

Clinical and psychological telemonitoring and telecare of high risk heart failure patients

We conducted a trial of telemonitoring and telecare for patients with chronic heart failure leaving hospital after being treated for clinical instability. Eighty patients were randomized before hospital discharge to a usual care group (n = 40: follow-up at the outpatient clinic) or to an integrated management group (n = 40: patients learned to use a handheld PDA and kept in touch daily with the monitoring centre). At enrolment, the groups were similar for all clinical variables. At one-year follow-up, integrated management patients showed better adherence, reduced anxiety and depression, and lower NYHA class and plasma levels of BNP with respect to the usual care patients (e.g. NYHA class 2.1 vs 2.4, P < 0.02). Mortality and hospital re-admissions for congestive heart failure were also reduced in integrated management patients (P < 0.05). Integrated management was more expensive than usual care, although the cost of adverse events was 42% lower. In heart failure patients at high risk of relapse, the regular acquisition of simple clinical information and the possibility for the patient to contact the clinical staff improved drug titration, produced better psychological status and quality of life, and reduced hospitalizations for heart failure.

Transthoracic bioimpedance and brain natriuretic peptide assessment for prognostic stratification of outpatients with chronic systolic heart failure

In patients with chronic heart failure, physical evaluation and clinical judgment may be inadequate for prognostic stratification.

Twenty-four hour ambulatory intra-arterial blood pressure in normotensive and borderline hypertensive subjects

A number of studies have shown that blood pressure values obtained by ambulatory monitoring are lower than those obtained in the doctors office by cuff readings. However, there is still no suitable information on `normal‘ 24-h ambulatory blood pressure values. In 19 normotensive and 13 borderline hypertensive subjects, defined by repeated office blood pressure measurements, we recorded intra-arterial blood pressure under ambulatory conditions for 24 h (Oxford method) in order (1) to assess the 24-h blood pressure values of normal subjects, and (2) to compare their 24-h blood pressure values with those of borderline hypertensive patients. In the normotensive subjects systolic, diastolic and mean ambulatory blood pressure values over 24 h were significantly lower than the corresponding office values, the differences being −15.0, −22.1 and −17.9 mmHg, respectively. In the borderline hypertensives 24-h ambulatory blood pressure was significantly lower than office readings. On average, the 24-h mean blood pressure of normotensive subjects was significantly lower than that of borderline patients (P < 0.01). However, individual 24-h blood pressure values showed a considerable overlap. Thus, (1) ambulatory blood pressure values just below 140/90 mmHg do not necessarily mean that the blood pressure is in the normal range, the mean 24-h blood pressure of true normotensive subjects being much lower; (2) ambulatory blood pressure monitoring in patients with high office blood pressure readings may help to identify subjects whose 24-h mean values are indistinguishable from those of normotensives. However, the clinical relevance of these findings in the diagnosis of hypertension has to be validated by prospective clinical trials.

Correlation between trans and intra-thoracic impedance and conductance in patients with chronic heart failure

Aims In chronic heart failure, changes of intra-thoracic impedance (Z0IT) may suggest impending pulmonary congestion; a similar result has been found by measuring trans-thoracic conductance (TFCTT = 1/Z0 = 1/k&OHgr;). We assumed that a relationship could exist between Z0IT and TFCTT. Methods We collected 140 measurements from 70 patients carrying an implantable cardioverter-defibrillator/cardiac resynchronization device with the CareLink function (71 ± 9 years, New York Heart Association (NYHA) 2.4 ± 0.9, ejection fraction 31 ± 8%, optimal treatment); they were studied during system alarms and after appropriate treatment (diuretics and/or vasodilators, n = 42) or during clinical stability and at the time of a system alarm (n = 28); correspondent BNP values were obtained. We related Z0IT obtained by the device, with TFCTT obtained with a commercial system. Results A strong relationship was found between Z0IT and TFCTT. Changes in the variables after treatment or during worsening conditions were of the same direction and order of magnitude, and were related to BNP levels obtained simultaneously. Conclusions Trans-thoracic conductance, similarly to intra-thoracic impedance, may noninvasively point to pulmonary congestion and be useful in patients not carrying an implanted device. The possibility of remotely obtaining this variable should be evaluated for the telemonitoring of heart failure patients.