Effects of Long-term Treatment with Prazosin on Left Ventricular Diastolic Function in Mild to Moderate Hypertension (12)

The reasons for this individual variability are not clear and it might be hypothesized that age, sex, duration of hypertension, individual genetic background, and neurohumoral influences can play an important role in affecting left ventricular mass under the same condition of blood pressure control.
It is known that the effect of blood pressure normalization on left ventricular mass occurs after a period of treatment whose length is variable according to the class of drugs used. Thus, it might be supposed that prazosin needs a longer time to produce an echocardiographically documentable effect. Nevertheless, no association has been demonstrated between left ventricular mass changes and follow-up length in our patients, as we observed for diastolic function. Even in those subjects treated for more than 12 months, a reduction of left ventricular mass or an improvement of left ventricular filling did not occur.

Effects of Long-term Treatment with Prazosin on Left Ventricular Diastolic Function in Mild to Moderate Hypertension (10)

However, only some of these factors have been thoroughly investigated, and therefore not all the mechanisms of derangement of early diastolic function have been clarified so far.
Most of the dynamic factors we were able to measure or estimate in this study were normal before the treatment and did not change after the treatment: systolic function indices, end-diastolic left ventricular dimensions and volumes (as indices of preload), and heart rate (as index of sympathetic drive to the heart). Dynamic exercise test and regional contractility (examined both with echocardiography and radionuclide techniques) were normal in all patients, both at the beginning and at the end of the study: we may therefore argue that the coronary blood flow was not significantly compromised in these patients. Afterload was decreased by the blood pressure reduction obtained with the treatment.

Effects of Long-term Treatment with Prazosin on Left Ventricular Diastolic Function in Mild to Moderate Hypertension (9)

Effects of Long-term Treatment with Prazosin on Left Ventricular Diastolic Function in Mild to Moderate Hypertension (9)Other recent studies did not observe a close relationship between left ventricular mass and diastolic function. Trimarco et al observed that treatment with a nonselective P-blocking agent improved diastolic function lowering blood pressure, but this effect was independent from left ventricular mass reduction. The study of Shahi et al showed that an angiotensin-converting enzyme inhibitor agent, alone or in addition of a diuretic, reduces left ventricular mass, but does not change left ventricular diastolic function.

Effects of Long-term Treatment with Prazosin on Left Ventricular Diastolic Function in Mild to Moderate Hypertension (8)

Even the individual behavior o£ diastolic function indices was widespread (Fig 2): PFR increased more than 10 percent in one subject, decreased in four subjects and did not change in sft subjects. A similar behavior was observed for FF Vz and tPFR, to6.
The relationship between diastolic function and left ventricular mass was analyzed: even in those patients whose left ventricular mass decreased more than 10 percent during treatment (three patients), no improvement of the left ventricular diastolic function indices was observed. No relationship was observed between diastolic function changes and the length of the period of treatment and the degree of blood pressure control.

Effects of Long-term Treatment with Prazosin on Left Ventricular Diastolic Function in Mild to Moderate Hypertension (7)

Effects of Long-term Treatment with Prazosin on Left Ventricular Diastolic Function in Mild to Moderate Hypertension (7)Individual behavior of cardiac morphology indices was widespread (Fig 1): left ventricular mass did not change in four patients and increased in four patients, while in the remaining three patients it showed a reduction. A similar behavior was observed for the other morphologic indices. No relationship was observed between changes in left ventricular mass and the length of the period of treatment and the degree of blood pressure control. The average values of systolic function indices did not change significantly during the treatment with prazosin.

Effects of Long-term Treatment with Prazosin on Left Ventricular Diastolic Function in Mild to Moderate Hypertension (6)

Pearsons linear regression was used to test the relationship between blood pressure, left ventricular mass, and indices of systolic and diastolic function. Significance was established at the level of p<0.05 (two-tailed analysis).
Results
Average blood pressure values significantly decreased during the treatment with prazosin: systolic blood pressure from 163.54 ±17.80 mm Hg to 146.81 ±13.14 mm Hg (p<0.01), and diastolic blood pressure from 106.09 ±6.96 mm Hg to 92.90 ±8.93 mm Hg (p<0.01). Heart rate values increased slightly, but the difference was not statistically significant (from 73.73 ±9.73 to 85.73 ± 16.00). Average values of cardiac morphology before and after antihypertensive therapy are shown in Table 1. The measurements of the left ventricular systolic and diastolic filling indices in the hypertensive subjects at the beginning and at the end of the study are shown in Table 2, which also includes the mean values from a group of 16 normal subjects of our laboratory.

Effects of Long-term Treatment with Prazosin on Left Ventricular Diastolic Function in Mild to Moderate Hypertension (5)

Effects of Long-term Treatment with Prazosin on Left Ventricular Diastolic Function in Mild to Moderate Hypertension (5)Using threshold and second-derivative technique, the left ventricular regions of interest were obtained. The time-activity curves were generated using these regions applied to the raw data and subtracting the background values. The ejection fractions were calculated from the time-activity curve in the usual manner (the end-diastolic count minus the end-systolic count divided by the end-diastolic count minus the background count). The rates and the other diastolic indices were obtained by the Fourier analysis (fourth harmonic) of the time-activity curves. The first derivative of the fitted curves provided the PFR (positive derivative) and PER (negative derivative), expressed in units of end-diastolic volume/s; the tPFR was measured from end-systole to the time at which the PFR occurred. The FF l/i is the fraction between the increase in count obtained at the first third of diastole and the total stroke count, expressed as a percentage. In our laboratory, intraobserver variability in the measurement of cardiac function has been established at less than 10 percent.

Effects of Long-term Treatment with Prazosin on Left Ventricular Diastolic Function in Mild to Moderate Hypertension (4)

Patients took their study medications on the day of the treatment echocardiogram. All echocardiograms were axled and read blindly in random sequence by a single observer (C.A.). In our laboratory, intraobserver variability in the measurement of left ventricular mass has been established at less than 7 percent; only changes of 10 percent or more thus have been considered as attributable to the effect of the drug.