Chronic Congestive Heart Failure Patients Research Articles

Hemodynamic responses during leg press exercise in patients with chronic congestive heart failure

To increase muscle mass and strength in patients with chronic congestive heart failure (CHF), there is a need for implementing resistance exercises in exercise training programs. This study sought to assess the safety of rhythmic strength exercise with respect to left ventricular function in 9 patients with stable CHF, compared with 6 stable coronary patients with mild left ventricular dysfunction (control group). With use of right-sided catheterization, changes in left ventricular function were assessed during double leg press exercise at loads of 60% and 80% of maximum voluntary contraction. The exercise sessions lasted 14 minutes each, divided into work and recovery phases of 60/120 seconds. In CHF, during exercise at a 60% load, there was a significant increase in heart rate (mean ± SEM 90 ± 4 beats/min; p <0.05), mean arterial blood pressure (95 ± 3 mm Hg; p <0.01), diastolic pulmonary artery pressure (20.2 ± 2.7 mm Hg; p <0.01), and cardiac index (3 ± 0.3 L/m 2/min; p <0.05). Additionally, during leg press exercise at an 80% load, there was a significant decrease in systemic vascular resistance (1,086 ± 80 dynes · s · cm −5; p <0.001), an increased cardiac index (3.4 ± 0.1; p <0.001), and left ventricular stroke work index (75 ± 5 g · m/m 2; p <0.01), suggesting enhanced left ventricular function. Compared with controls, in CHF the magnitude of changes in hemodynamic parameters during exercise, demonstrated at a 60% load, was significantly smaller (systemic vascular resistance: [mean] 1,613 → 1000 vs 1472 → 1,247 dynes · s · cm −5; cardiac index: 2.4 → 3 vs 2.8 → 4.4 L/m 2/min, and stroke work index: 60 → 69 vs 114 → 155 g · m/m 2; p <0.05 each). Nevertheless, changes indicated an enhanced contractile function of the left ventricle in CHF. This study demonstrates stability of left ventricular function during resistance exercise in well-compensated CHF patients with optimal drug therapy, as well as the appropriateness of the chosen mode and intensity applied as these factors relate to cardiovascular stress. This conclusion cannot be extrapolated to patients with less well-compensated heart failure, or to more protracted resistance training.

Ischemia and Left Ventricular Dysfunction

There is convincing evidence that (prolonged) episodes of myocardial ischemia lead to impairment of left ventricular (LV) function and ultimately to chronic congestive heart failure(CHF), but whether the opposite is also true has not been well established. We studied this issue in two groups of CHF patients with positron emission tomography (PET) by using [13N]ammonia (13NH3) as a tracer. In the first protocol we compared 12 patients with idiopathic dilated cardiomyopathy (who have normal coronary arteries) with 12 healthy controls. In the second protocol we studied a group of 24 patients with documented coronary artery disease (CAD). In this protocol, we compared patients with normal LV function to those with LV dysfunction and CHF. In patients with cardiomyopathy, myocardial blood flow at rest was normal but flow reserve (after dipyridamole infusion) was significantly impaired (1.7 ± 0.08) compared with normal subjects (2.7 ± 0.04; p <0.05). Furthermore, by examining [18F]fluorodeoxyglucose (18FDG) uptake, a perfusion-metabolism mismatch was observed in 24 ± 6% of the myocardium in patients with cardiomyopathy as opposed to 0% of normals (p <0.05). In patients with CAD, myocardial blood flow reserve (measured in non-stenotic arteries to non-infarcted area) was impaired in CHF patients (1.7 ± 0.06) compared to those with normal LV function (2.3 ± 0.05; p <0.05). In both groups of CHF patients, the impairment of blood flow reserve showed a significant correlation with the severity of CHF. In conclusion, myocardial blood flow reserve is impaired in patients with CHF in proportion to the degree of CHF. Metabolic studies with 18FDG further show that, in patients with idiopathic dilated cardiomyopathy and CHF, flow-metabolism mismatch is present in a substantial part of the myocardium, suggesting a pathogenetic role for ischemia.

Ischemia and left ventricular dysfunction: a reciprocal relation?

There is convincing evidence that (prolonged) episodes of myocardial ischemia lead to impairment of left ventricular (LV) function and ultimately to chronic congestive heart failure (CHF), but whether the opposite is also true has not been well established. We studied this issue in two groups of CHF patients with positron emission tomography (PET) by using [13N]ammonia (13NH3) as a tracer. In the first protocol we compared 12 patients with idiopathic dilated cardiomyopathy (who have normal coronary arteries) with 12 healthy controls. In the second protocol we studied a group of 24 patients with documented coronary artery disease (CAD). In this protocol, we compared patients with normal LV function to those with LV dysfunction and CHF. In patients with cardiomyopathy, myocardial blood flow at rest was normal but flow reserve (after dipyridamole infusion) was significantly impaired (1.7 +/- 0.08) compared with normal subjects (2.7 +/- 0.04; p <0.05). Furthermore, by examining [18F]fluorodeoxyglucose (18FDG) uptake, a perfusion-metabolism mismatch was observed in 24 +/- 6% of the myocardium in patients with cardiomyopathy as opposed to 0% of normals (p <0.05). In patients with CAD, myocardial blood flow reserve (measured in non-stenotic arteries to non-infarcted area) was impaired in CHF patients (1.7 +/- 0.06) compared to those with normal LV function (2.3 +/- 0.05; p <0.05). In both groups of CHF patients, the impairment of blood flow reserve showed a significant correlation with the severity of CHF. In conclusion, myocardial blood flow reserve is impaired in patients with CHF in proportion to the degree of CHF. Metabolic studies with 18FDG further show that, in patients with idiopathic dilated cardiomyopathy and CHF, flow-metabolism mismatch is present in a substantial part of the myocardium, suggesting a pathogenetic role for ischemia.

Attenuation of compensation of endogenous cardiac natriuretic peptide system in chronic heart failure: prognostic role of plasma brain natriuretic peptide concentration in patients with chronic symptomatic left ventricular dysfunction.

Patients with congestive heart failure (CHF) have high plasma levels of atrial natriuretic peptide (ANP), mainly from the atrium, and brain natriuretic peptide (BNP), mainly from the ventricle. We examined the prognostic role of plasma BNP in chronic CHF patients in comparison with plasma ANP and other variables previously known to be associated with high mortality. We also evaluated the relationship between mortality and plasma cGMP, a biological marker of ANP and BNP. The study subjects were 85 patients with chronic CHF (left ventricular ejection fraction <0.45) who were followed for 2 years. The plasma levels of ANP, BNP, cGMP, and norepinephrine increased with the severity of CHF. Among plasma levels of ANP, BNP, cGMP, and norepinephrine and clinical and hemodynamic parameters, only high levels of plasma BNP (P<.0001) and pulmonary capillary wedge pressure (P=.003) were significant independent predictors of the mortality in patients with CHF by Cox proportional hazard analysis. Although plasma levels of ANP and BNP were threefold or fivefold higher in nonsurvivors than in survivors, there was no difference in plasma cGMP level between nonsurvivors and survivors. These findings indicate that plasma BNP is more useful than ANP for assessing the mortality in patients with chronic CHF and that the plasma levels of BNP provide prognostic information independent of other variables previously associated with a poor prognosis. Our findings also suggest that the compensatory activity of the cardiac natriuretic peptide system is attenuated as mortality increases in chronic CHF patients with high plasma levels of ANP and BNP.

High-Resolution CT Scan in the Evaluation of Exercise-Induced Interstitial Pulmonary Edema in Cardiac Patients

To evaluate the onset of exercise-induced interstitial pulmonary edema in cardiac patients by high-resolution CT (HRCT). Prospective, normal controlled. Thirty subjects divided into three groups: group 1--10 outpatients with chronic congestive heart failure (CCHF), New York Heart Association (NYHA) class I; group 2--10 outpatients with CCHF, NYHA class II/III; and group 3 (control)--10 normal subjects. HRCT scans were obtained at rest and 4, 8, 12, 16, and 20 min after progressive treadmill exercise test. The following HRCT findings consistent with interstitial edema were significantly different (p<0.05) in group 2 when compared with groups 1 and 3: artery/bronchus ratio > 1 in the upper lobes, peripheral increase in the vascular markings, interlobular septal thickening, and peribronchial "cuffing." These differences were maximal at 12 min after exercise and returned to normal values after 20 min. Interstitial pulmonary edema was present immediately after exercise in CCHF patients. It may be important in the genesis of dyspnea of these patients.

Detection and significance of a discrete very low frequency rhythm in RR interval variability in chronic congestive heart failure

Although in advanced chronic congestive heart failure (CHF) very low frequency (<0.04 Hz, VLF) oscillations are prominent, the clinical importance and the physiologic basis of these rhythms have not been elucidated. To investigate the physiologic determinants of the VLF rhythms in RR interval variability, we studied 36 patients with stable, moderate to severe CHF (33 men, age: 58 ± 8 years, ejection fraction 25 ± 10%, peak oxygen consumption 18.1 ± 4.6 ml/kg/min) and 12 age- and sex-matched controls using autoregressive spectral analysis of RR interval, blood pressure, and respirator/ signals during controlled conditions. We quantified low frequency (LF) (0.04 to 0.15 Hz), high frequency (HF) (0.15 to 0.40 Hz), VLF, and total power (0 to 0.5 Hz), and calculated the coherence between systolic blood pressure and RR interval variability within each band. Peripheral chemosensitivity was assessed by the ventilatory response to hypoxia using transient inhalation of pure nitrogen. The influence of transient inactivation of peripheral chemoreceptors on the VLF rhythm was investigated by exposing 6 patients to hyperoxic (60% oxygen) conditions for 20 minutes. Twenty-three patients (64%) with CHF, but no controls, had a discrete VLF rhythm (0.019 ± 0.008 Hz) in RR variability. The presence of VLF rhythm was not related to any difference in clinical parameters (etiology, New York Heart Association class, ejection fraction, oxygen uptake) but rather to a different pattern in RR interval and blood pressure variability: lower LF power (2.8 ± 1.6 ms 2 natural logarithm [ln]) compared either to patients without VLF (4.0 ± 1.3 ms 2 ln) or to controls (5.9 ± 0.7 ms 2 ln), higher percentage of power within VLF band (86.3 ± 8.3% vs 77.5 ± 7.9% and 61.5 ± 14.1%) and a markedly impaired coherence between RR interval and systolic blood pressure variability within the LF band (0.26 ± 0.10 vs 0.42 ± 0.18 and 0.63 ± 0.15, in patients with vs without VLF peak and controls, respectively). Patients with VLF had significantly increased hypoxic chemosensitivity, and hyperoxic conditions were able to decrease VLF power and abolish the VLF rhythm in 5 of 6 patients with CHF. Discrete VLF oscillations in RR variability are common in patients with advanced CHF and appear to be related to severely impaired autonomic regulation and suppression of baroreceptor function, with enhancement of hypoxic chemosensitivity. We hypothesize that this rhythm represents an enhanced chemoreflex harmonic oscillation in CHF patients, which may have application for arrhyrhmogenesis.

Evaluation of Left Ventricular Mechanical Efficiency in the Human Heart by Echocardiography

It has been proved that ventricular systolic wall stress and myocardial mass are two major determinants of myocardial oxygen consumption (MVO2) in the intact human heart. The product of stress and mass, which we named the stress‐mass‐index (SMI), has the correct unit for work (cm X dyns/cm = dyns x cm), and is very similar to the pressure‐volume work of the heart. To examine whether SMI might be used as a predictor of MVO2, left ventricular mean systolic wall stress (Mσc,Mσm), left ventricular wall mass (Mm), and stroke work (SW) were measured by echocardiography in normal and diseased human hearts. The area bounded by the end‐diastolic and end‐systolic pressure‐volume lines, and the systolic segment of the pressure‐volume loop (PVA) were also measured in each subject. It has been proved repeatedly in the past that PVA correlates significantly with MVO2. Our results showed that there was a close correlation between PVA and SMI in every group (r − 0.76‐0.91, P &lt; 0.001 all), which proved indirectly that SMI may reflect MVO2. On this basis, left ventricular efficiency (Eff) was estimated as SW/SMI × 100%. Effin 30 patients with essential hypertension (17.1%± 1.6%) was normal compared to the control subjects (19.9%± 2.4%). However, Eff of 22 hypertensive patients with mild left ventricular dysfunction (13.3%± 2.1%), 33 coronary artery heart disease patients (10.8%± 1.8%), and 11 chronic congestive heart failure patients (6.6%± 2.1%) was significantly decreased compared to the control. These changes in Eff were in agreement with clinical findings and left ventricular ejection fractions (EF). For the first time, we have measured Eff noninvasively; the results are very close to those evaluated invasively in human hearts by others. This reflects the fact that it is possible to calculate Eff noninvasively. We conclude that the product of left ventricular systolic wall stress could reflect the change in MVO2 at rest. SW/SMI may be a useful method in evaluating Eff and ventricular function.

Health care delivery for chronic congestive heart failure in the United Kingdom.

Since the United Kingdom has fewer cardiology specialists than other countries, the United Kingdom cardiologist cannot provide direct care for all patients with chronic congestive heart failure (CHF). Most CHF care is provided by general practitioners, physicians or geriatricians. A survey of 100 CHF patients attending a health center revealed that these patients visited their general practitioners 270 times in 1 year, compared with only 34 outpatient visits. The cardiologist mainly provides echocardiography. The accurate diagnosis of mild CHF became imperative with the advent of angiotensin converting enzyme (ACE) inhibitors. Results of a survey showed that although 1.6% of the population are taking diuretics for CHF, only 0.84% of the population have left ventricular systolic dysfunction on echocardiography. An estimated 22 echocardiograms per 1000 population per year are required (10 for structural reasons, three for suspected new CHF, three to identify patients with a low left ventricular ejection fraction and six to identify left ventricular hypertrophy in hypertensive patients). However, district general hospitals in Scotland can only provide 3.3-6 echocardiograms per 1000 population per year. The elderly CHF patient may not receive adequate treatment because of the lack of resources and a dislike of 'overinvestigating' or 'overtreating' the elderly. The benefits of echocardiography and ACE inhibitor therapy for all patients with CHF should be stressed.

Exercise testing in heart failure. A critical review.

Exercise intolerance is one of the primary characteristics of chronic congestive heart failure (CHF). Therefore, exercise testing has been widely used in the assessment of CHF patients, both to define the severity of the disease and to assess the efficacy of pharmaceutical agents in clinical trials. A number of different exercise tests can be used, although maximal exercise testing is the most common. Maximal exercise capacity can be determined by measuring exercise duration during incremental exercise, or maximal oxygen (O2) consumption, or it can be estimated by anaerobic threshold. While baseline exercise testing in CHF patients accurately identifies and quantifies cardiac failure and determines prognosis, it is of limited value in assessing changes that occur as a result of drug therapy. A key drawback of exercise testing as a measurement of drug effect is the fact that exercise changes produced by drug intervention do not correlate well with changes in the mortality rate. Several examples of the lack of correlation between exercise testing and mortality rates have been observed in clinical trials with angiotensin converting enzyme (ACE) inhibitors and vasodilators. ACE inhibitors have a modest effect on maximal exercise capacity but they improve survival. It is thought that neuroendocrine activation more closely reflects mortality rates and also the changes in survival observed with pharmacological intervention compared with other modes of evaluation.

Cardiac secretion of atrial natriuretic factor with exercise in chronic congestive heart failure patients.

We have previously reported a fivefold increase of plasma atrial natriuretic factor (ANF) in patients with congestive heart failure (CHF) compared with normal subjects. However, given the marked increase of ANF under basal conditions, the extent to which ANF secretion can further increase under physiological stress is not been clarified in CHF. We therefore evaluated ANF secretion during ergometric exercise in 11 patients with CHF, with peripheral venous ANF samples obtained at rest and peak exercise. In seven patients, simultaneous peripheral venous and right ventricular ANF samples were obtained to estimate myocardial ANF secretion. Hemodynamic characteristics of exercise included a significant increase of heart rate, mean arterial pressure, and cardiac output (all P < 0.01); reduction of systemic vascular resistance (P < 0.001); and increase of right atrial and pulmonary wedge pressures (P < 0.001). ANF was abnormally elevated at baseline (108 +/- 58 fmol/ml) yet increased further to 183 +/- 86 fmol/ml with exercise (P < 0.003). A step-up of right ventricular ANF, particularly during exercise, was consistent with active myocardial secretion, despite elevated baseline ANF levels.

Endothelial function in chronic congestive heart failure

There is evidence that the endothelium plays an important role in the control of human vascular tone by releasing endothelium-derived nitric oxide. The hypothesis that an impairment of this mechanism is involved in the increased peripheral vasoconstriction of patients with chronic congestive heart failure (CHF) was tested. Acetylcholine and N-monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide synthesis from L-arginine, were infused in the brachial artery of healthy volunteer subjects (controls) and patients with severe CHF. The radial artery diameter was determined by a high-precision A-mode ultrasound device, using a 10 MHz probe. Forearm blood flow was calculated from vessel diameter and blood flow velocity measured simultaneously by Doppler. The blood flow response to acetylcholine was blunted in patients with CHF compared with that in control subjects. In contrast, the decrease in blood flow induced by L-NMMA was exaggerated in CHF, and the blood flow response to nitroglycerin was preserved. The changes in radial artery diameter induced by acetycholine and L-NMMA were not significant in control subjects and CHF patients, but dilation of the radial artery by nitroglycerin was significantly reduced in CHF. The results demonstrate an impaired endothelium-dependent dilation of forearm resistance vessels in CHF, suggesting a reduced release of nitric oxide on stimulation. In contrast, the basal release of nitric oxide from endothelium of forearm resistance vessels is preserved or may even be enhanced, and may play an important compensatory role in chronic CHF by antagonizing neurohumoral vasoconstrictor forces in CHF.

Differential hemodynamic effects of oral enoximone in severe congestive heart failure

Since impaired myocardial contractility is the primary deficit in a large number of patients with congestive heart failure (CHF), long-term treatment with oral positive inotropic agents has generated considerable interest over the last decade. A number of inotropic agents demonstrate salutary hemodynamic effects when administered short-term. 1 Benefits of long-term therapy are, however, unclear. 2,3 The dose of the inotropic agent may be crucial to its overall efficacy since serious side effects and even death may occur at high doses. 4 In a wide range of doses, both intravenous and oral forms of enoximone (an experimental phosphodiesterase inhibitor) exert positive inotropic, chronotropic and vasodilator effects in chronic CHF patients. 5,6 It has been shown that there is a plateau in the dose-effect relation of oral enoximone since doses in excess of 3.0 mg/kg do not offer any further hemodynamic benefit. 7 Additionally, doses in the 3 to 6 mg/kg range appear to have a very high incidence of adverse side effects. 8 The optimal dose of oral enoximone in chronic CHF is unknown. To determine whether the desirable and undesirable hemodynamic effects of oral enoximone are seen at different doses, we studied the short-term effects of various single doses (0.5 to 3.0 mg/ kg) of this drug in 65 patients with severe CHF.

Relationship Between Mixed Venous Oxygen Saturation and Cardiac Index in Patients with Chronic Congestive Heart Failure

The use of mixed venous oxygen saturation (SvO2) in patients with chronic congestive heart failure (CHF) has been advocated to analyze the action of therapy on cardiac index (CI). To evaluate the relationship between CI and SvO2, ten CHF patients (mean age 65 years) were studied before and one, two, three, four (T4), six, eight and 24 hours after oral administration of an angiotensin converting enzyme (ACE) inhibitor (perindopril, 4 mg). At T4, a 12 percent increase in CI (p less than 0.01) was associated with a 16 percent decrease in arteriovenous oxygen difference (p less than 0.01), a 13 percent increase in mixed venous oxygen pressure (PvO2) (p less than 0.01), and a 9 percent increase in SvO2 (p less than 0.05) with no significant change in arterial oxygen pressure. There was no correlation between CI and SvO2 (r = 0.22) and between CI and PvO2 (r = 0.23). Individual analyses were performed and patients were divided into two groups based on CI versus SvO2 r value; group 1, n = 6, r greater than 0.65 (0.65-0.90), group 2, n = 4, r less than 0.65 (0.14-0.20). The lack of correlation in group 2 was due to a drug-dependent increase in oxygen consumption (VO2) +18 percent vs -3 percent in group 1 (p less than 0.05) associated with a lack of increase in PvO2 +3 percent vs +14 percent in group 1 (p less than 0.05) despite a similar increase in oxygen availability +19 percent versus +16 percent. It was concluded that (1) a correlation between CI and SvO2 is not found in every patient with CHF; (2) the lack of correlation in four out of our ten patients was due to an associated and significant increase in CI and VO2 in group 2; (3) group 2 patients probably had an important oxygen debt before treatment; (4) SvO2 cannot be used instead of CI to determine the hemodynamic consequences of the use of cardiovascular drugs.

Regulation of glomerular filtration rate in chronic congestive heart failure patients

The purpose of this study was to identify the factor(s) that characterize impaired glomerular filtration rate (GFR) in congestive heart failure (CHF) patients. We studied 34 patients, measuring systemic hemodynamics, vasoactive hormones, and sodium and volume status. Renal plasma flow (para-aminohippurate) and GFR (inulin) were assessed by steady-state clearance techniques. Both linear and multiple regression analyses were performed. Impaired GFR was characterized by reduction of renal blood flow and renal fraction of cardiac output, and by an increase of renal vascular resistance. The correlation between GFR and filtration fraction (r = 0.492, P less than 0.003) indicated that individuals with greatest impairment of GFR had the lowest filtration fraction and increased overall renal vascular resistance, indicating dependence of GFR on afferent, rather than efferent vasoconstriction, under conditions of low renal perfusion. Mean vasoactive hormones and blood volume were increased, but without clear cut correlation with GFR. The greatest impairment of GFR was observed in elderly CHF patients, as renal blood flow and function demonstrated an age-dependent decline, in addition to the adverse effects of CHF. In a multiple regression model, renal blood flow and filtration fraction accounted for 69% and 25%, respectively, of the variability of GFR, with a co-linear influence of age. Thus, we have identified age-related, abnormal renal hemodynamic patterns in CHF, and the fragile nature of GFR in the elderly CHF population.

The ventilatory threshold: quantitative analysis of reproducibility and relation to arterial lactate concentration in normal subjects and in patients with chronic congestive heart failure

The present study evaluates optimal ventilatory criteria and exercise protocols for determining the ventilatory threshold, and assesses the day-to-day reproducibility of the ventilatory threshold and its relation to peak oxygen uptake V02 and blood lactate concentration in normal subjects and patients with stable chronic congestive heart failure (CHF). Eighteen normal subjects and 18 patients underwent rapid (1-minute stage) and gradual (3-minute stage) bicycle exercise tests on consecutive days. The ventilatory threshold was determined from computer-generated printouts of expired gas variables measured breath by breath. lnterobserver variability of ventilatory threshold was small in both normal (0.66 ± 0.85 ml/min/kg) and CHF patients (0.50 ± 0.46 ml/min/kg). Variability in the normal subjects was lower for the rapid exercise protocol (0.66 ± 0.85 ml/min/kg) than the gradual protocol (1.72 ± 1.63 ml/min/kg) (p <0.05), but both protocols produced similar results in the CHF group. Day-to-day reproducibility of ventilatory threshold was high (r = 0.91, standard error of the estimate 1.74 ml/min/kg) and was similar to that of peak V02 (r = 0.95, standard error of the estimate 3.31 ml/min/kg). The use of co-plotted ventilatory equivalents for oxygen and carbon dioxide yielded ventilatory threshold values comparable to values obtained by using multiple parameters (r = 0.94, p <0.0001). Although the ventilatory threshold did not predict a precise lactate level for individual subjects, the lactate increment at the ventilatory threshold occurred within a narrow range in both normal subjects and patients with CHF; the increase was 7.5 ± 4.5 mg/dl and 7.7 ± 4.1 mg/dl, respectively, indicating a relation to initial increases in blood lactate.

Assessment of autonomic regulation in chronic congestive heart failure by heart rate spectral analysis

Neurohumoral modulation of cardiovascular function is an important component of the hemodynamic alterations in patients with chronic congestive heart failure (CHF). Analysis of heart rate (HR) variability is a noninvasive means of investigating the autonomic control of the heart. The variability of HR and respiratory signals, both derived from ambulatory electrocardiographic recordings, were analyzed with power spectral analysis to evaluate autonomic control in 25 patients with chronic stable CHF (class III or IV) and 21 normal control subjects. In the patients with CHF, HR spectral power was markedly reduced (p < 0.0001) at all frequencies examined (0.01 to 1.0 Hz, period 1 to 100 seconds) and virtually absent at frequencies >0.04 Hz. Heart rate fluctuations at very low frequencies (0.01 to 0.04 Hz) less effectively differentiated CHF patients from control subjects, due to discrete (about 65 seconds, 0.015 Hz) oscillation in HR, which was associated with a similar pattern in respiratory activity in many of the patients with CHF. These findings demonstrate a marked derangement of HR modulation in patients with severe CHF. The frequency characteristics of HR fluctuations in these patients are consistent with abnormal baroreflex responsiveness to physiologic stimuli, and suggest that there is diminished vagal, but relatively preserved sympathetic, modulation of HR.

Noninvasive assessment of left ventricular wall stress in chronic congestive heart failure patients.

Therapy with prazosin can improve the condition of patients with congestive heart failure due to its vasodilating action. Therefore nine patients with volume overloaded left ventricles due to aortic insufficiency and mitral insufficiency received 1 mg. of prazosin four times a day for two weeks. Peak and end-systolic wall stress were estimated using a noninvasive echocardiographic technique. The peak systolic wall stress in this group was 155 x 10(3) dynes/cm2 which is similar to the reported normal value. However, the end systolic wall stress was 101 x 10(3) dynes/cm2 which is much higher than the reported normal values. Following the administration of oral prazosin, the end systolic stress was normalized while the peak systolic stress was reduced below normal. As a result of therapy with prazosin, the ejection fraction, the percentage of change in the minor axis, and the velocity of circumferential fiber shortening significantly increased. Thus, the oral administration of prazosin can improve left ventricular function in patients with mitral insufficiency and aortic insufficiency.

Hemodynamic effects of captopril in chronic heart failure: Efficacy of low-dose treatment and comparison with prazosin

The acute hemodynamic effects and long-term therapeutic actions of low doses of the oral angiotensin-converting enzyme (ACE) inhibitor captopril (CPT) were evaluated in 18 patients with severe chronic congestive heart failure (CHF). Increasing doses of 1, 2.5, 6.25, 12.5, and 25 mg of CPT were given at 2-hour intervals. Increased stroke volume index (SVI) and reduced mean pulmonary capillary wedge (PCW) pressure occurred at 1 hour ( p < 0.05) with an associated decline of blood pressure. Maximal hemodynamic improvement for the group was seen at 6 and 7 hours following the 6.25 and 12.5 mg doses when SVI was elevated 35% and mean PCW pressure decreased 40% from control. CPT in doses of 12.5 to 50 mg every 8 hours was continued long term in these 18 CHF patients. Four patients died, and one was noncompliant; drug therapy was withdrawn in two patients with symptomatic hypertension and in one patient who experienced an alteration in taste. The remaining 10 patients showed significant improvement in symptoms and treadmill exercise duration at 3 months after CPT therapy was started. Moreover, repeat hemodynamic measurements were similar to optimal measurements obtained during the initial study. In a further study, the acute hemodynamic and hormonal effects of sequentially randomized 5 mg prazosin and 25 mg CPT were compared in 10 CHF patients. While both drugs reduced PCW pressure and vascular resistance, CPT effects were greater. Further, CPT alone effected a small rise in cardiac index and minor decline in heart rate, and CPT diminished aldosterone levels and increased plasma renin activity while prazosin did not.

Determinants of clinical response and survival in patients with congestive heart failure treated with captopril

The efficacy of chronic ambulatory captopril (CPT) therapy was evaluated over an 18-month period in 36 patients with refractory chronic congestive heart failure (CHF) by cardiac catheterization, treadmill exercise, nuclear scintigraphy, echocardiography, and symptomatology. Clinical improvement to New York Heart Association functional class I or class II was observed in 63% of the patients (20 of 32) after 2 months of treatment; this amelioration of CHF symptoms was sustained in 63% of the patients (10 of 16) at 18 months. Exercise tolerance increased in 64% of the patients (16 of 25) at early follow-up and in 79% (11 of 14) at late follow-up. Univeriate analysis revealed that the pre- and post-CPT stroke work indices (SWI) and the post-CPT cardiac index related to favorable long-term clinical response. Fourteen CHF patients (39%) died during the 18-month follow-up. Univariate analysis revealed that the pretreatment SWI, right atrial pressure, plasma norepinephrine concentration, and echocardiographic shortening fraction were significant predictors of mortality. Multivariate analysis indicated that the SWI was the principal determinant of survival: the 18-month cumulative survival rate for CHF patients with a SWI less than 32 gm · m/m 2 was 44% compared to 88% when the SWI was greater than 32 gm · m/m 2. Thus, CPT results in sustained symptomatic and functional improvement in patients with advanced CHF, but the mortality remains high and is primarily related to the severity of cardiac dysfunction.

Noninvasive Assessment of Load Reduction in Chronic Congestive Heart Failure Patients

Therapy with phentolamine can improve the condition of patients with congestive heart failure due to the inotropic effect of this drug as well as its vasodilating action. Therefore, 8 patients with volume-overloaded left ventricles due to aortic insufficiency and mitral insufficiency received 50 mg of phentolamine 4 times a day for 2 weeks. Peak and end systolic wall stress were estimated using a noninvasive echocardiographic technique. The peak systolic wall stress in this group was 133 X 10(3) dynes/sq cm, which is similar to the reported normal value. However, the end systolic wall stress was 89 X 19(3) dynes/sq cm, which is much higher than the reported normal values. After PO administration of phentolamine, the end systolic stress was normalized while the peak systolic stress was reduced below normal. As a result of therapy with phentolamine, the ejection fraction, the percentage of change in the minor axis, and the velocity of circumferential fiber shortening significantly increased. Thus, PO administration of phentolamine can improve left ventricular function in patients with mitral insufficiency and aortic insufficiency.