Felodipine in patients with chronic heart failure: discrepant haemodynamic and clinical effects.

Previous open studies have suggested that felodipine, a selective calcium antagonist and vasodilator, may be useful in the treatment of heart failure. A double blind placebo controlled crossover trial was therefore conducted to investigate the clinical and haemodynamic effects of felodipine in 15 patients with chronic ischaemic heart failure in New York Heart Association symptom class III. Felodipine significantly increased resting and exercise (25W bicycle ergometry) cardiac output without producing concomitant changes in resting or exercise heart rate or right and left ventricular filling pressures. Felodipine did not significantly improve symptom scores or exercise capacity in the group as a whole. It also resulted in significant fluid retention as shown by a rise in ankle circumference, body weight, and a fall in haematocrit. Further research is required to elucidate the mechanism that is responsible for the discrepancy between the haemodynamic and clinical effects of felodipine in patients with moderately severe heart failure.     

Short-term haemodynamic effects of dopexamine in patients with chronic congestive heart failure

Dopexamine (FPL 60278) is a new dopamine analogue which possessesa combination of dopamine receptor and beta-2-adrenoreceptoragonist properties. The aim of our study was to evaluate theshort-term haemodynamic effects of dopexamine administered byintravenous infusion at different dosage rates. Eight patientswith chronic congestive heart failure were studied. A dose of1 µg kg^–1 min^–1 produced a 27% decrease insystemic vascular resistance index (32.6 to 23.9 res. unitsm², P<0.001 and a significant increase in cardiac index (2.7to 3.61min^–1 m^–2, P<0.001). Stroke volume indexand heart rate increased significantly by 22% and 7%, respectively.An increase in left ventricular stroke work index was also seenat the dose level inducing the maximum cardiac output. Leftventricular filling pressures and arterial blood pressures werenot affected. We conclude that administration of dopexamineto patients with congestive heart failure augments cardiac performanceat rest.     

Acute haemodynamic effects of oestrogen administration in male patients with chronic heart failure

BACKGROUND: Although there are many studies concerning the effects of long-term oestrogen administration on systemic haemodynamics in postmenopausal women, the effects of oestrogen in patients with chronic heart failure are not defined. AIM: The goal of this study was to evaluate the acute haemodynamic effects of oestrogen in male patients with chronic heart failure. METHODS AND RESULTS: We studied 15 men with advanced heart failure (NYHA II-IV, EF < 35%). A Swan-Ganz thermodilution catheter was advanced in their pulmonary artery and central haemodynamics were assessed at baseline, after placebo administration, and following 0.625 and 1.25 mg of oestrogen infusion. Simultaneously, all patients underwent limb plethysmography. Analysis of variance with repeated measures was used to compare the sequential measurements. Following oestrogen administration, right atrial, pulmonary artery and pulmonary capillary wedge pressures, as well as systemic, pulmonary and forearm vascular resistance were decreased; cardiac output, cardiac index, stroke volume, stroke volume index, stroke work index and forearm blood flow were increased. CONCLUSIONS: In male patients with chronic heart failure, acute oestrogen administration improves the indices of cardiac systolic performance and decreases pulmonary and systemic vascular resistance. These findings imply a beneficial effect of oestrogen in selected patients with chronic heart failure.     

Beneficial haemodynamic effects of insulin in chronic heart failure

OBJECTIVE—To characterise the central and regional haemodynamic effects of insulin in patients with chronic heart failure.
DESIGN—Single blind, placebo controlled study.
SETTING—University teaching hospital.
PATIENTS—Ten patients with stable chronic heart failure.
INTERVENTIONS—Hyperinsulinaemic euglycaemic clamp and non-invasive haemodynamic measurements.
MAIN OUTCOME MEASURES—Change in resting heart rate, blood pressure, cardiac output, and regional splanchnic and skeletal muscle blood flow.
RESULTS—Insulin infusion led to a dose dependent increase in skeletal muscle blood flow of 0.36 (0.13) and 0.73 (0.14) ml/dl/min during low and high dose insulin infusions (p < 0.05 and p < 0.005 v placebo, respectively). Low and high dose insulin infusions led to a fall in heart rate of 4.6 (1.4) and 5.1 (1.3) beats/min (p < 0.05 and p < 0.005 v placebo, respectively) and a modest increase in cardiac output. There was no significant change in superior mesenteric artery blood flow.
CONCLUSION—In patients with chronic heart failure insulin is a selective skeletal muscle vasodilator that leads to increased muscle perfusion primarily through redistribution of regional blood flow rather than by increased cardiac output. These results provide a rational haemodynamic explanation for the apparent beneficial effects of insulin infusion in the setting of heart failure.


Keywords: blood flow; heart failure; insulin; muscle     

Acute haemodynamic effects of testosterone in men with chronic heart failure.

AIMS: Anabolic therapy with testosterone may be useful in the treatment of wasting associated with chronic heart failure but little is known about its cardiovascular actions. The aim of this study was to determine the acute haemodynamic effects of testosterone administration in men with heart failure. METHODS AND RESULTS: Twelve men with stable chronic heart failure were enrolled in a double-blind, randomised, placebo-controlled, cross-over trial. Subjects were given testosterone 60 mg or placebo via the buccal route and central haemodynamics were monitored over 6h, using a pulmonary flotation catheter. Subjects received the second treatment on day 2 and haemodynamic monitoring was repeated. Treatment was well tolerated. Compared with placebo, testosterone treatment resulted in a relative increase in cardiac output (p<0.0001, ANCOVA), with maximum treatment effect after 180 min (10.3+/-4.6% increase from baseline, p=0.035; 95% CI 0.8-19.8). This was accompanied by reduction in systemic vascular resistance compared with baseline (p<0.0001, ANCOVA), with maximum treatment effect also at 180 min (-17.4+/-9.6% from baseline, p=0.085; 95% CI -37.3 to +2.6). These maximal changes coincided with the peak elevation in serum bio-available testosterone. There was no significant change in any other haemodynamic parameter measured. CONCLUSIONS: Administration of testosterone increases cardiac output acutely, apparently via reduction of left ventricular afterload.     

Comparison of haemodynamic effects of oral hydralazine and prazosin hydrochloride in patients with chronic congestive heart failure

The comparative haemodynamic effects of oral prazosin hydrochloride and hydralazine were evaluated in 11 patients with chronic congestive heart failure. The maximum total dose of prazosin received by an individual varied up to 25 mg. Ten patients received a maximum of 75 mg and one received 50 mg of hydralazine at six-hour intervals. There was no significant change in heart rate with either drug. Decrease in mean arterial and left ventricular filling pressures were modest and similar with both agents. With prazosin, the average cardiac index increased 20 per cent and systemic vascular resistance decreased 20 per cent. By contrast, hydralazine increased cardiac index by 58 per cent and decreased systemic vascular resistance by 40 per cent. The increase in stroke work and stroke volume indices was significantly greater with hydralazine than with prazosin. These findings suggest that in some patients with severe chronic congestive heart failure, improvement in left ventricular performance may be greater with hydralazine than with prazosin.     

Additive haemodynamic effects of piroximone and prostacyclin in severe chronic heart failure

This study was undertaken to assess the haemodynamic effectsof the combined infusion of prostacyclin and piroximone, a phosphodiesteraseinhibitor, in 18 patients with severe congestive heart failure.Right heart catheterization was performed with a Swan-Ganz thermodilutioncatheter and arterial blood pressure was monitored using a radialline. After baseline haemodynamic measurements, prostacyclinwas administered in all patients at the incremental infusionrate of 2, 4, 6 and 8 and 10 ng. kg^–1. min^–1 during15min each. After recovery of baseline haemodynamics, patientswere randomly assigned to the piroximone infusion rate of 5or 10µg. kg^–1. min^–1 or placebo. After 24h piroximone or placebo infusion, the same prostacyclin protocolwas applied. Prostacyclin infusion added to piroximone resultedin a significant improvement in haemodynamics, as compared tothe group receiving prostacyclin added to placebo. As comparedto the curve observed with the placebo infusion, 10 ng. kg^–1.min^–1 prostacyclin infusion resulted in a further increasein cardiac index, by 41 and 38% (P<0·01) at the piroximone-infusionrates of 5 and 10 ng. kg^–1. min^–1, respectively,whereas systemic vascular resistance decreased by 25 and 21%,respectively (P<0·01). Additionally, a further decreasein pulmonary capillary wedge pressure by 13 and 11% (P<0·05)and in pulmonary vascular resistance by 21 and 19% (P<0·05)was observed at the piroximone-infusion rates of 5 and 10µig.Kg^–1. min^–1, respectively. Consequently, strokework index increased significantly, as compared to the groupreceiving prostacyclin added to placebo. This haemodynamic improvementoccurred without significant changes in heart rate and meanarterial pressure. Thus, this study shows that in patients withsevere congestive heart failure, short-term infusion of prostacyclinis safe and has additive haemodynamic effects on phosphodiesteraseinhibitors.     

Comparison of haemodynamic effects of oral hydralazine and prazosin hydrochloride in patients with chronic congestive heart failure.

The comparative haemodynamic effects of oral prazosin hydrochloride and hydralazine were evaluated in 11 patients with chronic congestive heart failure. The maximum total dose of prazosin received by an individual varied up to 25 mg. Ten patients received a maximum of 75 mg and one received 50 mg of hydralazine at six-hour intervals. There was no significant change in heart rate with either drug. Decrease in mean arterial and left ventricular filling pressures were modest and similar with both agents. With prazosin, the average cardiac index increased 20 per cent and systemic vascular resistance decreased 20 per cent. By contrast, hydralazine increased cardiac index by 58 per cent and decreased systemic vascular resistance by 40 per cent. The increase in stroke work and stroke volume indices was significantly greater with hydralazine than with prazosin. These findings suggest that in some patients with severe chronic congestive heart failure, improvement in left ventricular performance may be greater with hydralazine than with prazosin.     

Failure of dopexamine to maintain haemodynamic improvement in patients with chronic heart failure

Ten patients with chronic heart failure were given a continuous infusion of dopexamine after an initial stage of dose titration. On the dose selected the cardiac index initially rose by 56%, as a result of an increase in both heart rate and stroke volume index. Systemic vascular resistance fell by 34% and the mean arterial pressure did not change. Within 18 hours of the start of the continuous infusion, however, all the variables except heart rate had returned to preinfusion values. Nine of the 10 patients were withdrawn from the 48 hour study, six because of haemodynamic deterioration and two because of side effects. If the premature loss of therapeutic effect reflects an intrinsic property of this agent, dopexamine may be of limited clinical value.     

Resting and exertional haemodynamic effects of buccal nitroglycerin: acute and chronic discontinuous treatment in post-myocardial infarction patients with heart failure

The resting and exertional haemodynamic effects of acute and chronic discontinuous (one tablet every 6 h) treatment with 5 mg of buccal nitroglycerin (BN) have been assessed in nine postinfarction heart failure patients. At rest, pulmonary artery (PAP), pulmonary wedge (PWP), and right atrial pressures (RAP) were reduced by 42%, 55% and 77%, respectively, after the first dose and by 26%, 32% and 45%, respectively, after the chronic (three weeks) treatment with BN. During exercise, at the same workload, PAP, PWP and RAP were significantly reduced by 44%, 54% and 62%, respectively, after acute treatment and by 28%, 34% and 44%, respectively, after chronic treatment. The maximal workload (Kgm) increased by 179% and 166% and the exercise time increased by 78% and 71% after acute and chronic therapy, respectively. At the maximal workload, after acute BN, overall haemodynamics were better than in the basal state. PAP, PWP and RAP were still reduced by 19%, 31% and 31%, respectively, after acute treatment, while after chronic phase the results did not differ from control. The severity of cardiac failure, according to the Weber classification, was reduced by acute and chronic therapy. We can conclude that the buccal nitroglycerin showed clear efficacy in improving overall haemodynamic parameters both at rest and during exercise in post-myocardial infarction patients with heart failure. The discontinuous treatment maintained the effect of nitroglycerin without clear evidence of tolerance during chronic therapy.     

Failure of dopexamine to maintain haemodynamic improvement in patients with chronic heart failure.

Ten patients with chronic heart failure were given a continuous infusion of dopexamine after an initial stage of dose titration. On the dose selected the cardiac index initially rose by 56%, as a result of an increase in both heart rate and stroke volume index. Systemic vascular resistance fell by 34% and the mean arterial pressure did not change. Within 18 hours of the start of the continuous infusion, however, all the variables except heart rate had returned to preinfusion values. Nine of the 10 patients were withdrawn from the 48 hour study, six because of haemodynamic deterioration and two because of side effects. If the premature loss of therapeutic effect reflects an intrinsic property of this agent, dopexamine may be of limited clinical value.     

Acute haemodynamic and metabolic effects of dopexamine, a new dopaminergic receptor agonist, in patients with chronic heart failure

Dopexamine, a new compound with postjunctional dopamine receptor activating and beta adrenoceptor agonist properties, was given to 10 patients with chronic heart failure at diagnostic cardiac catheterisation to investigate its acute haemodynamic and metabolic effects. The drug was administered by intravenous infusion in three incremental doses and produced significant dose related increases in cardiac index, stroke volume index, and heart rate and falls in systemic vascular resistance and left ventricular end diastolic pressure; aortic and pulmonary artery pressures were unchanged. Isovolumic phase (max dP/dt and KVmax) and ejection phase (peak aortic blood velocity, maximum acceleration of blood, and maximum rate of change of power with time during ejection) indices of myocardial contractility were all increased by dopexamine but these changes were hard to interpret in the presence of an increase in heart rate. Myocardial efficiency and ejection fraction were both increased and left ventricular end diastolic and end systolic volumes fell. These largely beneficial changes were achieved without a statistically significant increase in myocardial oxygen consumption or disturbance of myocardial metabolic function. Dopexamine was well tolerated but tremor was reported by two patients at the intermediate dose and mild chest pain by two patients at the high dose.     

Felodipine in severe chronic congestive heart failure: Acute effects on central hemodynamics and regional blood flow distribution

Summary In order to assess the effect of felodipine, a new calcium antagonist with vascular selectivity, on regional blood flow distribution at rest in chronic congestive heart failure, ten patients were studied during an acute test. Right heart catheterization allowed the evaluation of hemodynamic parameters; renal blood flow was calculated using paraamino-hippuric acid clearance; hepatic blood flow measurement was based on indocyanine green clearance; and limb blood flow was assessed with venous occlusion plethysmography. Blood samples were collected for the analysis of plasma catecholamines, renin, and aldosterone. All parameters were recorded in duplicate under basal conditions and after felodipine infusion.The infusion of felodipine induced a significant increase in cardiac index, stroke work index, and limb blood flow. Systemic and pulmonary arterial blood pressure, pulmonary wedge pressure, and systemic resistance underwent a significant decrease. The heart rate, pulmonary resistance, renal blood flow, and hepatic blood flow were not changed.In conclusion, felodipine was of benefit in congestive heart failure at rest in an acute test, acting through a marked decrease in vascular resistance and a consequent improvement in cardiac output and limb blood flow. No changes in renal and hepatic blood flow were observed.Part of these data have been presented at the Second Cardiovascular Pharmacotherapy International Symposium, San Francisco, CA, 1987.     

Minoxidil in patients with chronic left heart failure: contrasting hemodynamic and clinical effects in a controlled trial

Minoxidil, a potent predominant arterial dilator, improves hemodynamics over the short term in patients with heart failure. In random double-blind fashion 17 patients with chronic left heart failure were given minoxidil (nine patients) or placebo (eight patients) in addition to digoxin and diuretics for 3 months. Cardiac index and heart rate increased and mean arterial pressure and systemic vascular resistance fell within 4 hr of minoxidil administration. Right heart and pulmonary arterial pressures were unchanged over the short term but rose after long-term minoxidil. After 3 months of minoxidil treatment, systemic vascular resistance was still reduced (11.7 +/- 6.3[SD] vs 17.1 +/- 3.1 U at baseline; p less than .05). Hemodynamics were similar at baseline and remained unchanged during placebo treatment. Mean left ventricular ejection fraction rose from 29.6 +/- 17.7% to 42.7 +/- 22.3% (p less than .05) after 3 months of minoxidil treatment (this result was influenced largely by responses in two patients), and remained unchanged (at 25.1 +/- 16.6%) after 3 months of placebo. Exercise duration and maximal oxygen uptake during exercise were unchanged during minoxidil or placebo treatment. Total clinical events, including increased need for diuretics, angina, ventricular arrhythmias, worsening heart failure, and death were all more frequent during minoxidil vs placebo administration (21 vs seven total events; p less than .01). Thus, despite improving hemodynamics and left ventricular function, long-term minoxidil administration was associated with a poorer clinical course in patients with chronic left ventricular failure. Furthermore, this experience demonstrates that improvement of left ventricular function alone cannot be reliably interpreted as proof of clinical efficacy of therapeutic interventions in patients with heart failure.     

Acute and chronic haemodynamic effects of biventricular pacing and of switching to different pacing modalities in heart failure patients

BACKGROUND: In patients with severe heart failure, sinus rhythm and wide QRS complex biventricular (BiV) pacing leads to clinical and haemodynamic improvement, but the immediate reversibility of these changes is not known. METHODS: We assessed the acute and medium-term (3-month) haemodynamic effects of BiV pacing and of switching to other pacing modalities in 21 patients with severe heart failure, sinus rhythm and QRS>or=130 ms. Haemodynamic studies were performed: 1) at the time of implantation of a BiV pacing device, during AAI pacing, atrial synchronous right ventricular (RV) pacing, atrial synchronous left ventricular (LV) pacing and atrial synchronous BiV pacing (all at 100 bpm); 2) after 3 months of continuous BiV pacing--with evaluations being made by switching to RV and the other pacing modalities. RESULTS: At both the acute and medium-term evaluations, BiV pacing provided the greatest improvement in cardiac index. Switching from BiV to RV pacing led to a more marked decrease in the cardiac index at 3 months. No strict correlation was evident between acute and medium-term effects of BiV pacing on cardiac index. CONCLUSION: Cardiac resynchronization by BiV pacing provides acute/medium-term improvements in cardiac index. Sudden, medium-term failure of LV stimulation can lead to an even more pronounced haemodynamic derangement than that inducible by RV pacing at baseline. Acute haemodynamic evaluations do not seem to provide a powerful way for identifying medium-term responders.     

Comparison of haemodynamic effects of oral prazosin, oral hydralazine, and intravenous nitroprusside in same patients with chronic heart failure

The haemodynamic effects of oral prazosin and hydralazine were evaluated in patients with refractory heart failure and compared with those of intravenous nitroprusside in the same patients. Both oral agents were well tolerated and appeared to have beneficial haemodynamic effects. Prazosin and hydralazine produced similar increases in cardiac output associated with a similar decrease in systemic vascular resistance. Prazosin and hydralazine produced similar increases in cardiac output associated with a similar decrease in systemic vascular resistance. Prazosin resulted in a more significant decline in left ventricular filling pressure and pulmonary vascular resistance than did hydralazine. Haemodynamic alterations induced by prazosin were similar to those induced by nitroprusside, which suggests a relatively balanced reduction of preload and afterload. With hydralazine, the increase in cardiac output without change in left ventricular filling pressure or pulmonary vascular resistance suggests minimal effect on preload but significant reduction in afterload.     

Acute haemodynamic and metabolic effects of dopexamine, a new dopaminergic receptor agonist, in patients with chronic heart failure.

Dopexamine, a new compound with postjunctional dopamine receptor activating and beta adrenoceptor agonist properties, was given to 10 patients with chronic heart failure at diagnostic cardiac catheterisation to investigate its acute haemodynamic and metabolic effects. The drug was administered by intravenous infusion in three incremental doses and produced significant dose related increases in cardiac index, stroke volume index, and heart rate and falls in systemic vascular resistance and left ventricular end diastolic pressure; aortic and pulmonary artery pressures were unchanged. Isovolumic phase (max dP/dt and KVmax) and ejection phase (peak aortic blood velocity, maximum acceleration of blood, and maximum rate of change of power with time during ejection) indices of myocardial contractility were all increased by dopexamine but these changes were hard to interpret in the presence of an increase in heart rate. Myocardial efficiency and ejection fraction were both increased and left ventricular end diastolic and end systolic volumes fell. These largely beneficial changes were achieved without a statistically significant increase in myocardial oxygen consumption or disturbance of myocardial metabolic function. Dopexamine was well tolerated but tremor was reported by two patients at the intermediate dose and mild chest pain by two patients at the high dose.