Paul Broadhurst

VALUE OF CARVEDILOL IN CONGESTIVE HEART FAILURE SECONDARY TO CORONARY ARTERY DISEASE

Despite considerable interest in the use of beta-blocking agents in congestive heart failure (CHF), their clinical application is limited because of their negative inotropic effects. Beta blockers with vasodilating properties may have the advantage of overcoming this, however. Carvedilol, a beta-blocking agent with vasodilating properties, was evaluated in 17 patients with chronic CHF secondary to ischemic heart disease with a resting left ventricular ejection fraction less than or equal to 45%, who were being maintained on diuretics. Exercise testing, radionuclide ventriculography, and right-sided cardiac catheterization were performed and intraarterial blood pressure measured before and after 8 weeks of carvedilol therapy in a dosage of 12.5 to 50.0 mg twice a day. Twelve patients completed the study and 5 withdrew. Symptomatic and hemodynamic improvement was demonstrated in 11 of the 12 patients. Heart rate and intraarterial blood pressure were both reduced by chronic therapy. Mean +/- standard deviation exercise time improved from 4.3 +/- 1.6 to 7.1 +/- 2.7 minutes (p less than 0.0001), as did resting left ventricular ejection fraction, from 27 +/- 9 to 31 +/- 11% (p less than 0.02). Pulmonary arterial wedge pressure fell from 19 +/- 7 mm Hg to 12 +/- 5 mm Hg (p less than 0.001) and total systemic vascular resistance from 1,752 +/- 403 to 1,497 +/- 310 dynes/s/cm-5/m2 (p less than 0.02). Stroke volume index improved also, from 31 +/- 6 ml to 40 +/- 6 ml (p less than 0.0005). These hemodynamic changes were mediated partly by vasodilation, diminished myocardial oxygen demand and reduction of sympathetic overactivity in the failing heart. These data suggest that carvedilol may have beneficial effects in patients with chronic CHF secondary to coronary artery disease.

Ambulatory intra-arterial blood pressure in normal subjects

It has been suggested that ambulatory blood pressure monitoring is superior to casual cuff methods in predicting cardiovascular events, but lack of reference data from a normal population seriously limits this methods clinical applicability. We therefore performed 24-hour intra-arterial ambulatory blood pressure (BP) monitoring in 50 normal volunteers (cuff BP less than 140/90 mm Hg) whose ages ranged from 18 to 74 years. There were 30 men and 20 women in the study, but there was no significant difference between the sexes with respect to age, cuff BP, or body mass index. A diurnal variation in BP was observed, qualitatively similar to that seen in hypertensive individuals, including a prewaking BP rise. Mean daytime intra-arterial pressures differed little between the sexes (124/74 mm Hg for women and 127/76 mm Hg for men, p = NS), but was lower at night in women than in men (96/52 versus 102/59 mm Hg, respectively; p less than 0.02 for diastolic pressure). Based on this group of subjects, we defined the upper limit of normal daytime BP in both men and women as 150/90 mm Hg and the upper limit of mean nighttime BP as 130/80 mm Hg for men and 115/65 mm Hg for women. The lower nighttime pressures in women compared with their male counterparts with similar daytime pressures may explain why women appear to tolerate similar levels of BP better than men.

The effects of intravenous carvedilol, a new multiple action vasodilatory β-blocker, in congestive heart failure

Recent studies have shown that β-blockers may be effective in the management of heart failure. However, negative inotropic effects of these agents may offset the beneficial properties of up-regulation of the β-receptors and reduction in myocardial oxygen demand. Carvedilol is a new drug which possesses a balanced combination of vasodilatation and β-blockade. Previous studies have shown that carvedilol may have beneficial effects on left ventricular function in patients with ischemic heart disease. We have performed a preliminary study to address the safety and acute effects of intravenous carvedilol in 17 patients with chronic congestive heart failure secondary to ischemic heart disease. Acute hemodynamic changes were monitored by right heart catheterization and arterial cannulation. Ejection fraction was also monitored by radionuclide ventriculography. Significant reductions in heart rate (79 ± 14 to 72 ± 12 beats/min, plt; 0.001) systolic and diastolic blood pressure (137 ± 20/ 72 ± 8 to 119 ± 19/66 ± 8 mm Hg, p < 0.001 and p < 0.01), systemic vascular resistance (1766 ± 367 to 1518 ± 377 dynes/s/cm−5/m2, p < 0.001) and pulmonary artery wedge pressure (20 ± 8 to 15 ± 7 mm Hg, p < 0.001) were observed. Ejection fraction increased significantly from 24 to 28% (p < 0.001) but there was little change in cardiac index or stroke volume index. The peak changes occurred at 10 min and the effect on pulmonary wedge pressure was maintained up to 30 min. No adverse effects were noted. The improvements in left ventricular filling pressure and systolic function, and the reduction in sympathetic activity may combine to produce an important therapeutic advantage in congestive heart failure. Further studies with this interesting agent are recommended.

Effectiveness of the once-daily calcium antagonist, lacidipine, in controlling 24-hour ambulatory blood pressure

The efficacy of the new once-daily dihydropyridine calcium antagonist, lacidipine, in reducing ambulatory intraarterial blood pressure (BP) was examined in 12 untreated hypertensive patients. The intraarterial recording was commenced 24 hours before the first 4-mg dose and was continued for a further 24 hours thereafter. After dose titration and chronic therapy, a second 24-hour ambulatory BP recording was made. There was a steady onset of drug action, maximal at 2 hours, but with reflex tachycardia after the first dose. Chronic administration reduced BP throughout the 24-hour period, without tachycardia. Mean daytime reduction in BP was 20 mm Hg systolic (p less than 0.005) and 12 mm Hg diastolic (p less than 0.02). Mean nighttime reduction was 8-mm Hg systolic (p less than 0.05) and 6-mm Hg diastolic (difference not significant). There was no postural decrease in BP on 60 degrees head-up tilting and hypotensive action was maintained during isometric exercise (reduction at peak of 32/18 mm Hg, p less than 0.05) and throughout dynamic exercise (reduction at peak of 23/14 mm Hg, p less than 0.05). Lacidipine is an effective once-daily antihypertensive agent, with good control of stress response.

Effects of noninvasive ambulatory blood pressure measuring devices on blood pressure

Abstract It is well recognized that the act of blood pressure (BP) measurement may influence the level of BP. 1 This “cuff response” is attributed to an alerting reaction; it does not decrease with repeated measurement, and is worse in the presence of a doctor than in the presence of a nurse. 2 This suggests that the major component of the reaction is not discomfort from inflation of the cuff, and this is supported by the fact that BP usually increases before the cuff is applied. These observations have led to the assumption that ambulatory cuff BP devices do not provoke such effects. This is implicit in the high reproducibility of measurements in groups of subjects that has been observed with some modern machines, 3 although this could simply reflect the reproducibility of the alerting response. This issue has only been addressed in subjects confined to bed for relatively brief periods. 4 No account has been taken of the possibility of effects on patients trying to sleep at night, or of the overall impact of wearing such devices. Ambulatory BP monitors are coming into wide use for the assessment of hypertensive subjects before and after treatment. This follows observations that ambulatory measurements are better prognostic indicators than casual readings. 5 This study tests the hypothesis that wearing an ambulatory cuff BP monitor might, in itself, alter BP by increasing discomfort, influencing activity or sleep patterns, or by promoting an alerting response.

Non-invasive ambulatory blood pressure monitors : a cautionary note

Physicians are encouraged to use ambulatory recorders as part of their evaluation of the midly hypertensive patient. But is the information that these machines provide accurate, and is the time and expense of the procedure justified? In short, should ambulatory monitoring be performed on the larger number of mildly hypertensive patients in order to identify the significant minority who are «white coat» responders?

Twenty-four hour ambulatory blood pressure profile of a new, sustained-release preparation of nicardipine

SummaryThe 24-hour blood pressure (BP) profile of a new sustained-release preparation of nicardipine was assessed in 16 patients with essential hypertension (supine cuff diastolic BP>95 mmHg). Twenty-four hour ambulatory intraarterial BP monitoring (Oxford system) before treatment revealed a mean (SD) daytime BP of 174 (19) mmHg systolic and 105 (8) mmHg diastolic, and a mean nighttime BP of 142 (26) mmHg systolic and 83 (12) mmHg diastolic. Sustained release nicardipine (60 mg) was administered twice daily for 4–6 weeks and the ambulatory BP monitoring repeated. No significant change in heart rate occurred throughout the 24-hour period. However, there was a significant reduction (p<0.0001) in the mean daytime BP of 21 (13) mmHg systolic and 12 (9) mmHg diastolic and of mean nighttime BP of 21 (15) mmHg systolic and 13 (11) mmHg diastolic. A similar reduction in hourly mean BP occurred throughout the whole 24-hour period, including the steep early morning rise in BP. Although vasodilatory-type side effects occurred, they were generally mild to moderate and transient. This preparation produces a significant reduction in BP throughout the 24-hour period without reflex tachycardia.

Activity of cardiac enzymes measured in the coronary sinus in acute myocardial infarction

Three patients with acute infarction of the anterior wall of the heart underwent catheterisation of the coronary sinus. Samples were taken for estimation of activity of cardiac enzymes. A small gradient was demonstrated between the sinus and the venous blood, suggesting that the coronary sinus is the conduit by which these enzymes are liberated into the systemic circulation.