Severe Chronic Congestive Heart Failure Research Articles

Comparative hemodynamic and clinical effects of long-term treatment with prazosin and captopril for severe chronic congestive heart failure secondary to coronary artery disease or idiopathic dilated cardiomyopathy

Short- and long-term hemodynamic and clinical responses to sequential therapy with prazosin (15 mg/day for 3 to 12 weeks) and captopril (75 to 300 mg/day for 2 to 15 weeks) were compared in 22 patients with severe chronic congestive heart failure. First doses of prazosin produced marked increases in cardiac index and stroke volume index (p < 0.01), but these effects were lost during long-term treatment. First doses of captopril produced only modest increases in both variables, but these persisted without attenuation during prolonged therapy. Both drugs produced immediate decreases in left ventricular filling pressure, mean arterial pressure, mean right atrial pressure and systemic vascular resistance; these changes became significantly attenuated (p < 0.01) with prazosin but not with captopril. At the end of treatment, stroke volume index was significantly higher and right and left ventricular filling pressures were significantly lower with captopril than with prazosin (p < 0.05 to 0.01). Only 8 of the 22 patients (36%) treated with prazosin benefited clinically, whereas 14 of 19 patients (74%) treated with captopril felt that they had improved (p < 0.05). These differences could not have been predicted by comparing responses to first doses of the 2 drugs. These findings indicate that the choice of 1 vasodilator drug over another in patients with congestive heart failure should be based on studies that compare their long-term rather than short-term hemodynamic and clinical effects.

Adverse influence of baroreceptor dysfunction on upright exercise in congestive heart failure

To test the hypothesis that baroreceptor autoregulation is an important determinant of exercise performance, the hemodynamic responses to the gravitational stress of head-up tilt and upright exercise were assessed in 41 patients with severe chronic congestive heart failure. Three patterns of autonomic dysfunction during head-up tilt were identified. Group A patients had near-normal circulatory reflexes whereas Group B patients experienced orthostatic hypotension and Group C patients lacked the afferent stimulus of venous pooling, Group A patients had a significantly longer exercise duration than both Groups B and C (607 ± 104 versus 330 ± 86 and 365 ± 53 seconds, respectively, p <0.05) and a significantly higher double product at peak exercise (17,779 ± 956 versus 12,235 ± 869 and 13,760 ± 998, respectively, p <0.05). Thus, baroreceptor abnormalities in the autoregulatory response to postural change are important determinants of the cardiovascular responses required during exercise and influence exercise performance. These abnormalities may help clarify the discrepancies between supine and upright exercise performance and may influence the long-term efficacy of vasodilator therapy in chronic congestive heart failure.

'Biological' depression; because sleep fails?

Although converting-enzyme inhibition is of established value in the management of patients with severe chronic congestive heart failure, troublesome adverse reactions occur frequently during the course of treatment and may cause physicians to interrupt effective therapy. The three most common adverse reactions that are seen in patients with heart failure following treatment with captopril and enalapril (symptomatic hypotension, functional renal insufficiency, hyperkalaemia) are predictable consequences of interfering with the homeostatic functions of the renin-angiotensin system, which evolved millions of years ago to preserve life in sodium-depleted states. It is not surprising, therefore, that these untoward effects can be prevented or reversed by increasing the dietary intake of salt or reducing the dose of concomitantly administered diuretics; their occurrence rarely requires discontinuation of drug therapy. Recognition of this link between sodium balance and the adverse effects of converting-enzyme inhibition is important, because most patients with severe heart failure who experience such untoward reactions can nevertheless be expected to improve clinically during long-term therapy, if effective treatment is not interrupted.

Hemodynamic factors limiting the response to transdermal nitroglycerin in severe chronic congestive heart failure

To clarify the continuing controversy concerning the use of transdermal nitroglycerin (MN), the short-term hemodynamic responses to sublingual, oral and transcutaneous nitrates were evaluated and compared in 22 patients with severe chronic congestive heart failure. Sixteen patients showed favorable hemodynamic effects with TDN, but the doses needed to achieve this response varied greatly: 10 mg/24 hours in 6 patients, 20 mg/24 hours in 5 patients, 40 mg/24 hours in 3 patients and 60 mg/24 hours in 2 patients. Of the 6 remaining patients, 3 did not respond to high-dose TDN even though they showed marked effects after sublingual and oral nitrate administration; 3 others did not respond to any nitrate formulation by any route. TDN produced immediate increases in cardiac index and decreases in right and left ventricular filling pressure, mean arterial pressure and systemic vascular resistance (p < 0.01). These effects, however, became rapidly attenuated within 3 to 6 hours; hours; after 18 to 24 hours, only modest decreases in right and left ventricular filling pressures were observed. After removal of TDN treatment, rebound decreases in cardiac index and rebound increases in mean arterial pressure and systemic vascular resistance occurred, but right and left ventricular filling pressures returned to pretreatment values without rebound changes. isosorbide dinitrate, 40 mg orally, produced hemodynamic effects that were greater in magnitude than effects seen after administration of TDN (p < 0.05 to 0.01), but 4 patients in whom tolerance to TDN developed showed reversible cross tolerance to oral isosorbide dinitrate. In conclusion, the use of TDN in patients with severe chronic congestive heart failure is limited by the large doses of the drug that are needed in some patients, by the rapid attenuation of its beneficial effects during prolonged therapy, by the potential for cross tolerance to other nitrates, and by the occurrence of rebound phenomena after drug withdrawal.

Provocation of hyper- and hypokalemic sudden death during treatment with and withdrawal of converting-enzyme inhibition in severe chronic congestive heart failure

Provocation of hyper- and hypokalemic sudden death during treatment with and withdrawal of converting-enzyme inhibition in severe chronic congestive heart failure

Severe atherosclerotic coronary arterial narrowing and chronic congestive heart failure without myocardial infarction: Analysis of 18 patients studied at necropsy

Observations are reported on 18 patients (aged 38 to 73 years ([mean 58]; 16 [89%] men) studied at necropsy who had had chronic congestive heart failure (CHF) more than 3 months In duration, >75% cross-sectional area (XSA) narrowing of 1 or more of the 4 major epicardial coronary arteries, and no left ventricular fibrosis or necrosis. Duration of symptoms from onset of CHF to death ranged from 0.3 to 13 years (mean 5.7). Angina pectoris occurred In 2 patients (11%). The mode of death was CHF in 12 (67%), sudden (arrhythmia) In 5 (28%), and emboli in 1 (5%). Heart weight ranged from 410 to 890 g (mean 632). Of 72 major epicardial coronary arteries (right, left main, left anterior descending, left circumflex) in the 18 patients, 30 (42%) were narrowed 76 to 100% In XSA by atherosclerotic plaque (right = 10, left main = 0, left anterior descending = 9 and left circumflex = 11). A mean of 1.7 of 4 major epicardial coronary arteries per patient were narrowed 76 to 100% in XSA by atherosclerotic plaque. In 10 patients, each 5-mm segment of the 4 major coronary arteries was examined histologically (mean 53 per patient): 23 segments (3%) were narrowed 96 to 100 % in XSA by atherosclerotic plaque; 58 (11%), 76 to 95; 93 (18%), 51 to 75 6k; 209 (40%), 26 to 50%, and 146 (28%), 0 to 25%. Left and right ventricular thrombi were found in 9 patients (50%); of the 9 patients, 1 had a systemic embolus; of the 9 patients without intraventricular thrombi, none had systemic emboli. Because grossly visible myocardial lesions were absent, the severe chronic CHF in these 18 patients cannot reasonably be attributed to coronary artery disease. It is most reasonable to believe that this group of patients had Idiopathic dilated cardlomyopathy and the coronary artery disease was coincidental.

Spectrum of acute hemodynamic effects of nifedipine in severe congestive heart failure

The acute hemodynamic effects of 20 to 50 mg of orally administered nifedipine were evaluated in 31 patients with severe chronic congestive heart failure (CHF) and the results were analyzed according to the response of the cardiac index (CI). Although the group mean value of CI increased significantly after nifedipine treatment (from 2.1 ± 0.5 to 2.4 ± 0.8 liters/min/m 2, p < 0.001), the individual response was variable. Twenty of the patients had 15% or greater increase in CI (group A) and 11 patients had less than a 15% increase or a decrease in CI (group B). Marked differences were also noted in the effects of nifedipine on other hemodynamic variables. Stroke volume increased 29 ± 14% in group A and decreased 11 ± 18% in group B (p < 0.001). Systemic vascular resistance decreased 34 ± 11% in group A (p < 0.001) and increased slightly, 2 ± 28%, in group B. Left ventricular (LV) stroke work index increased 11 ± 19% in group A (p < 0.001) and decreased markedly in Group B (21 ± 20%). Six group B patients had a substantial worsening (20% or more) of one or more hemodynamic measurements, including CI, stroke volume index, LV stroke work index and mean pulmonary artery wedge pressure. A comparison of control hemodynamic values at rest, LV ejection fraction, associated coronary artery disease, nifedipine dose, and concomitant diuretic therapy revealed no significant differences between the 2 groups. This study confirms, in a large group of patients with severe CHF, the variable hemodynamic effects of nifedipine therapy. Although CI improved in many patients, in some patients (35%) did not. Moreover, nifedipine therapy resulted in a significant hemodynamic deterioration in 6 patients. The response to therapy was not dose-related and could not be predicted by baseline hemodynamics, LV function, presence of associated coronary artery disease and concomitant diuretic therapy. Caution and hemodynamic monitoring are recommended if this agent is used in patients with severe chronic CHF.

Hemodynamic and hormonal effects of high-dose transdermal nitroglycerin in patients with chronic congestive heart failure

The hemodynamic effect of a large dose of nitroglycerin (NTG) (90 mg) given transdermally using a reservoir system was studied in 10 patients with severe, long-standing congestive heart failure. Serial hemodynamic measurements over 24 hours revealed a mild decrease in mean pulmonary artery wedge pressure. However, the change from baseline was significant only at 2 hours (19 ± 9 vs 27 ± 6 mm Hg). Mean right atrial pressure fell 1 hour after initiation of therapy, from 12 ± 7 to 8 ± 5 mm Hg. However, the change from control was not statistically significant. No significant changes were noted in heart rate, mean blood pressure, cardiac index, and systemic and pulmonary vascular resistance. Individual analysis of the effect of transdermal NTG on pulmonary artery wedge pressure demonstrated at 20% or greater reduction in 8 of 10 patients. However, persistent effect (longer than 8 hours) was seen in only 4 patients. Removal of NTG patches at 24 hours did not result in hemodynamic rebound. Serum catecholamine levels and renin concentration did not change 2 hours and 24 hours after initiation of NTG therapy or after removal of NTG patches. Thus, a large dose (90 mg) of transdermal NTG using a reservoir system results in mild and mostly statistically insignificant hemodynamic effect in patients with chronic severe congestive heart failure. Although a reduction in pulmonary artery wedge pressure is seen in most patients, rapid attenuation of this response is found in many patients and the effect only rarely lasts for 24 hours. The lack of hemodynamic rebound after discontinuation of therapy in addition to the absence of changes in serum catecholamine levels and renin concentration suggest that hemodynamic attenuation is not a result of activation of vasoconstrictive mechanisms during continuous NTG therapy.

Effects of Converting-Enzyme Inhibition on Cardiorenal Hemodynamics in Patients with Chronic Congestive Heart Failure

The role of the renin-angiotensin system in cardiorenal function in patients with severe chronic congestive heart failure was investigated. A single oral dose of captopril in 16 patients significantly increased cardiac index and reduced arterial blood pressure and total systemic vascular resistance. These changes were significantly greater in subjects with higher baseline plasma renin activity (PRA). During 7-day captopril therapy, renal plasma flow distinctly increased in 10 patients in whom renal function was followed. The increase found in renal plasma flow was greater in subjects with higher PRA. Yet, the reduction in renal vascular resistance was much greater than that of total systemic vascular resistance, even in patients with lower PRA. Simultaneous infusion of aprotinin in eight of these subjects did not affect the captopril-induced increase in renal plasma flow, despite the suppression of plasma bradykinin levels; these responses were the same in both PRA subgroups. The results suggest that captopril reduces total systemic vascular resistance in patients with chronic congestive heart failure through inhibition of the renin-angiotensin system and that the preferential renal vasodilator effect of captopril might be the sole result of this inhibition, with the kallikrein-kinin system or kinin-mediated prostaglandins not playing a major role.

Sublingual nifedipine: Acute effects in severe chronic congestive heart failure secondary to idiopathic dilated cardiomyopathy

Nine patients with chronic, severe (New York Heart Association class III to IV) congestive heart failure were studied to determine the acute effects of 10 mg of sublingual nifedipine on left ventricular (LV) function. Hemodynamic and echocardiographic data were obtained at rest and 30 minutes, 1, 2, 4 and 6 hours after nifedipine. Measurements at rest reflected LV dysfunction with elevation of end-diastolic volume index (102 ± 46 ml/m 2), pulmonary capillary wedge pressure (17 ± 8 mm Hg), systemic vascular resistance (1,547 ± 439 dynes s cm −5) and reduction of cardiac index (2.8 ± 0.5 liters/ min/m 2). There were no adverse effects noted with administration of sublingual nifedipine. Initial changes through 1 hour reflected an unloading effect of nifedipine with reduction in pulmonary capillary wedge pressure (11 ± 5 mm Hg) (p < 0.05), systemic vascular resistance (1,179 ± 289 dynes s cm −5) (p < 0.01), end-diastolic volume index (91 ± 37 ml/m 2 [difference not significant]) and an increase in cardiac index (3.6 ± 0.7 ml liters/min/m 2) (p < 0.01). Subsequently the cardiac index, systemic vascular resistance and end-diastolic volume index returned toward baseline. Only the pulmonary capillary wedge and pulmonary artery pressures demonstrated a sustained reduction through the 6-hour study period suggesting an effect of nifedipine on LV relaxation. Thus, sublingual nifedipine administered acutely to patients with clinical congestive heart failure is a safe and efficacious vasodilator.

Acute dose range study of milrinone in congestive heart failure

To determine the magnitude and time course of the optimal acute hemodynamic response to oral milrinone, an ascending dose range study was performed in 34 patients with severe chronic congestive heart failure (2.5 to 10 mg, n = 21; 7.5 to 15 mg, n = 13). With the 7.5- and 10-mg doses in both groups, cardiac index increased 26%, pulmonary capillary wedge pressure decreased 25% and systemic vascular resistance decreased 20%, with peak effect at 90 minutes. The hemodynamic improvement with 10 mg was sufficient to normalize cardiac index in 29% of patients. There was a clear dose-response relation, with the largest increases of cardiac index seen with the 15-mg dose (1.67 ± 0.10 to 2.31 ± 0.11; p < 0.005). This dose-response relation was confirmed by the correlation of drug levels and change in cardiac index. However, some patients had significant hypotension and tachycardia with the 15-mg dose. Thus, although 10 mg appears to be optimal for most patients, the dose of milrinone should be individualized for all patients.

Renal hemodynamic effects of vasodilation with nifedipine and hydralazine in patients with heart failure

The central and renal hemodynamic effects of nifedipine were evaluated in nine patients with severe chronic congestive heart failure. Oral nifedipine (34 +/- 22 mg, mean +/- standard deviation) was associated with a decrease in systemic vascular resistance from 1,748 +/- 436 to 1,321 +/- 302 dynes . s . cm-5 (p less than 0.001) and mean arterial blood pressure from 96 +/- 11 to 87 +/- 6 mm Hg (p less than 0.05) and with an increase in cardiac output from 4.2 +/- 1.1 to 4.9 +/- 1.2 liters/min (p less than 0.001). Although renal vascular resistance decreased from 11,988 +/- 2,256 to 10,286 +/- 3,011 dynes . s . cm-5 (p less than 0.05), no significant change was seen in renal blood flow (599 +/- 120 to 640 +/- 162 ml/min), glomerular filtration rate (62 +/- 18 to 62 +/- 17 ml/min), filtration fraction (18 +/- 5 to 17 +/- 6%), the ratio of renal/systemic vascular resistance (7.0 +/- 1.0 to 7.9 +/- 1.8) and the ratio of renal blood flow/cardiac output (0.15 +/- 0.02 to 0.13 +/- 0.03). Intravenous hydralazine (10 +/- 5 mg), given to eight of the patients in a randomized crossover design, resulted in a larger increase in cardiac output than did nifedipine (38 +/- 7 versus 19 +/- 10%, p less than 0.001) and in an increase in total renal blood flow from 570 +/- 152 to 645 +/- 174 ml/min (p less than 0.001). Renal vascular resistance decreased from 12,080 +/- 2,934 to 10,153 +/- 2,372 dynes . s . cm-5 (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Failure of low doses of amrinone to produce sustained hemodynamic improvement in patients with severe chronic congestive heart failure

Although amrinone produces acute hemodynamic improvement in patients with severe chronic congestive heart failure (CHF), it has not produced clinical benefits in long-term controlled trials. To determined if the administration of subtherapeutic doses of amrinone may account for its lack of efficacy in these studies, the dose requirements of the drug were investigated in 30 patients with severe CHF. Doses of 100 mg of oral amrinone produced moderate increases in cardiac index (0.35 liters/min/m2) and decreases in pulmonary capillary wedge pressure (6.8 mm Hg) and systemic vascular resistance (16%) (all p less than 0.01); these effects, however, were short-lived (less than 2.5 hours). Doses of 200 mg of oral amrinone produced marked increases in cardiac index (0.56 liters/min/m2) and substantial decreases in left ventricular filling pressure (9.9 mm Hg) and systemic vascular resistance (30%) (all p less than 0.01), and these effects persisted for longer than 4 hours. Only 4 patients showed hemodynamic responses with 100 mg of the drug that were sufficiently marked and long-lasting to merit chronic therapy, whereas 28 patients had such a response with the 200-mg dose. When 200 mg of amrinone was administered orally every 8 hours, sustained hemodynamic benefits were seen for 48 hours. However, 16 of 22 patients who received 600 mg of the drug daily for more than 1 week had intolerable adverse reactions that required drug withdrawal. In conclusion, hemodynamically effective doses of amrinone (600 mg/day) cannot be tolerated for long periods by most patients with severe chronic CHF.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of captopril on arterial and venous pressure, renal function, and humoral factors in severe chronic congestive heart failure.

The effects of captopril in several humoral factors were studied to elucidate the role of the renin-angiotensin (RA) system in arterial and venous pressures and renal function in patients with severe chronic congestive heart failure. A single oral dose of captopril in 20 subjects reduced mean arterial blood pressure from 77 to 67 mm Hg; this decrease correlated with baseline plasma renin activity (PRA). The increase in PRA and the decrease in plasma aldosterone levels after captopril were much greater in subjects with higher PRA. Plasma norepinephrine (NE) levels decreased, while those of epinephrine did not change. Peripheral venous pressure declined from 107 to 77 mm H2O; this decrease correlated with the change in NE levels. During 7-day captopril therapy, urine volume and sodium excretion increased (1145 to 1136 ml/day and 76 to 94 mEq/day) in 11 subjects in whom renal function was followed. Renal plasma flow (RPF) rose from 237 to 364 ml/min, while glomerular filtration rate did not change; the filtration fraction decreased from 32% to 23%. Simultaneous infusion of aprotinin in six of the subjects did not affect the captopril-induced increase in RPF, despite the suppression of plasma bradykinin levels. These results suggest that captopril reduces arterial blood pressure in patients with high PRA through inhibition of the RA system and dilates veins by attenuation of sympathetic nervous activity. Increased RPF and urinary sodium excretion induced by captopril might result from inhibition of the RA system; the kallikrein-kinin system or bradykinin-mediated prostaglandins do not appear to play a major role.

Acute hemodynamic and hormonal response to indoramin in congestive heart failure.

Acute hemodynamic and hormonal responses to a single dose of indoramin, an alpha 1-antagonist, were evaluated in 11 subjects with severe chronic congestive heart failure. A hemodynamic effect began within 1 hr of indoramin and persisted during the 6 hr of hemodynamic monitoring. Decreased right and left ventricular filling pressures were associated with increased stroke index and decreased pulmonary and systemic vascular resistances. Heart rate did not increase despite a fall in systemic arterial pressure. Forearm blood flow, forearm venous capacitance, and plasma norepinephrine levels were unchanged, whereas plasma renin activity rose from 12.7 +/- 17.4 to 16.6 +/- 20.4 ng/ml/hr. The only side effect was drowsiness in five of the 11 subjects. Our data demonstrate the acute effectiveness of indoramin in reducing ventricular preload and systemic vascular resistance in heart failure.

Differences in hemodynamic response to vasodilation due to calcium channel antagonism with nifedipine and direct-acting agonism with hydralazine in chronic refractory congestive heart failure

The hemodynamic response to a similar reduction of systemic vascular resistance after nifedipine and hydralazine administration was compared in a randomized crossover protocol in patients with severe chronic congestive heart failure (CHF). All 15 patients showed a 25% or greater reduction in vascular resistance with intravenous hydralazine (5 to 30 mg) and 11 patients showed a similar response with oral nifedipine (20 to 50 mg). In the latter 11 patients, despite similar reductions in systemic vascular resistance (35 ± 2% with nifedipine and 36 ± 4% with hydralazine, difference not significant), nifedipine resulted in a smaller increase in stroke volume index (from 23 ± 2 to 30 ± 2 ml/m 2 and from 24 ± 2 to 34 ± 2 ml/m 2 with hydralazine, p <0.05), cardiac index (from 2.0 ± 0.1 to 2.6 ± 0.2 liters/min/m 2 with nifedipine and from 2.0 ± 0.1 to 2.8 ± 0.2 liters/min/m 2 with hydralazine, p <0.05) and stroke work index (from 25 ± 3 to 27 ± 3 gm/m 2 with nifedipine and from 26 ± 2 to 32 ± 2 gm/m 2 with hydralazine, p <0.05). The decrease in blood pressure after nifedipine was slightly but not significantly larger than that with hydralazine (13 ± 3% vs 8 ± 2%). The changes in right atrial pressure, pulmonary artery wedge pressure and pulmonary vascular resistance were similar. The 4 patients who did not reduce their systemic vascular resistance by at least 25% with nifedipine had a worsening of their hemodynamic state as evidenced by 1 or more of the following findings: elevation of vascular resistance, decrease in cardiac index and increase in pulmonary artery wedge pressure. These results suggest that nifedipine exerts a clinically important negative inotropic effect in patients with severe chronic CHF that is only partially offset by its strong arteriolar dilatory effect. Hydralazine appears to be better than nifedipine when left ventricular afterload-reducing therapy is indicated in patients with severe CHF.

Estimation of angiotensin II receptor activity in chronic congestive heart failure

The renin-angiotensin system has been shown to participate in the pathophysiology of chronic heart failure in many patients. However, the immediate assessment of this contribution in individual patients may sometimes be difficult. As a pharmacologic estimate of angiotensin II receptor activity, we infused the angiotensin II analogue, saralasin, in 20 patients with severe chronic congestive heart failure (CHF). The infusion resulted in blood pressure responses ranging from an agonist pressor response (increased systemic resistance) in patients with low intrinsic renin-angiotensin system activity, to an antagonist depressor response (decreased systemic resistance) in patients with marked activation of the renin-angiotensin system. The ability of the saralasin response to pharmacologically estimate angiotensin II receptor activity in CHF was further revealed by two physiologic maneuvers that decrease endogenous circulating angiotensin II and angiotensin II receptor occupancy. Both converting enzyme inhibition with captopril and sodium repletion, factors known to decrease endogenous angiotensin II activity, provoked agonist responses to saralasin infusion. Furthermore, saralasin was able to reverse the orthostatic hypotension precipitated by converting enzyme inhibition of angiotensin-dependent vascular tone. In summary, saralasin provided a means to estimate angiotensin receptor activity and may therefore serve as a probe of angiotensin-mediated vasoconstriction in the pathophysiology of chronic CHF.

Comparison of hemodynamic responses to nifedipine and nitroprusside in severe chronic congestive heart failure

The hemodynamic effects of 20 to 40 mg of oral nifedipine were compared with those of intravenous nitroprusside in 11 patients with severe chronic congestive heart failure (CHF). In each patient, both drugs were administered to produce similar reduction of systemic vascular resistance (SVR) (29 ± 13% with nifedipine and 29 ± 12% with nitroprusside, difference not significant [NS]). At this comparable decrease in systemic vascular resistance, significant differences in hemodynamic responses to both drugs were noted: Nifedipine caused a smaller increase in cardiac index (20 ± 20% vs 40 ± 24%, p < 0.02) and a larger decrease in mean blood pressure than nitroprusside (16 ± 9% vs 8 ± 10%, p < 0.05). In addition, nifedipine produced a smaller decrease in mean pulmonary artery wedge pressure (13 ± 24% vs 36 ± 21%, p < 0.001) and pulmonary vascular resistance than nitroprusside (6 ± 42% vs 26 ± 46%, NS. Mean right atrial pressure decreased with nitroprusside, from 10 ± 7 to 5 ± 3 mm Hg (p < 0.05), but not with nifedipine (10 ± 7 mm Hg before and after nifedipine administration, NS). Left ventricular stroke work index increased with nitroprusside (20 ± 8 to 27 ± 9 g- m/ m 2, p < 0.05), but did not change with nifedipine (21 ± 9 vs 21 ± 10 g- m/ m 2, NS). These data show that nifedipine has an arteriolar dilatatory action in patients with CHF. However, compared with nitroprusside, nifedipine had a significantly larger hypotensive effect and had a lesser effect on right and left ventricular filling pressure, cardiac output and left ventricular function.

Acute Hemodynamic Effects of Nitrendipine in Chronic Congestive Heart Failure

The acute hemodynamic response to a single oral dose of nitrendipine (10-20 mg) was evaluated in eight subjects with severe chronic congestive heart failure during right heart catheterization. A hemodynamic effect began within 1 h. At peak effect (1-2 h after drug administration), mean arterial pressure fell from 84.0 +/- 9.2 to 76.0 +/- 9.2 mm Hg (mean +/- SD), right arterial pressure from 10.6 +/- 5.9 to 8.0 +/- 7.1 mm Hg, mean pulmonary arterial pressure from 35.5 +/- 9.2 to 30.1 +/- 9.4 mm Hg, pulmonary wedge pressure from 23.6 +/- 6.7 to 17.7 +/- 6.3 mm Hg, and cardiac index rose from 1.91 +/- 0.38 to 2.45 +/- 0.34 L/min/m2. Heart rate did not change (85 +/- 18 to 82 +/- 18 beats/min) despite the significant fall in arterial pressure. Systemic and pulmonary vascular resistances fell significantly. Whereas forearm blood flow increased from 1.44 +/- 0.52 to 2.06 +/- 0.41 ml/min/100 g (p less than 0.05), hepatic and renal blood flows were unchanged. This study demonstrates the acute effectiveness of nitrendipine in reducing ventricular preload and impedance in heart failure and in increasing cardiac output that appears to be preferentially directed to the skeletal bed. The left-upward shift of the Frank-Starling curve suggests the absence of any clinically important negative inotropic effect of nitrendipine. Nitrendipine therefore may be a useful agent for vasodilator therapy of heart failure.

Acute and chronic effects of sustained action buccal nitroglycerin in severe congestive heart failure

Vasodilators, such as nitroglycerin, have been widely used in the treatment of acute and chronic heart failure for therapeutic manipulation of the venous and arterial circulations to improve left ventricular function. We have tested the efficacy of a new formulation for sustained release buccal delivery of nitroglycerin (biological life 5–6 hr) in 21 patients with severe congestive heart failure due to ischaemic cardiomyopathy using maximal treadmill exercise testing and radionuclide angiography. A single-blind placebo-controlled acute and an open chronic phase (4 weeks) of treatment were employed. The mean dose was 23.4 mg daily, and clinical assessment suggested significant improvement in 15 patients. The mean ejection fraction (placebo) of 14.1%±1.6 SEM increased to 19.1%±1.7 (acute) and to 21.6%±1.7 (chronic treatment) ( P<0.001; n = 16). The mean exercise time increased from 3.02 ± 0.4 min (basal) to 5.95 ± 0.6 min (chronic) ( P < 0.001). Segmental wall motion abnormality was shown to improve after treatment for 4 weeks. There were no major side effects. Nine patients were reassessed after 24 weeks on the same regimen; exercise time and left ventricular ejection fraction were similar to the 4-week period, thus demonstrating a sustained improvement in cardiac function and functional capacity. A worthwhile functional and objective haemodynamic improvement was demonstrated in these patients with severe chronic congestive heart failure. This mode of treatment may have useful therapeutic value in the management of patients with a wide range of ischaemic heart failure.