Angiotensin-converting enzyme inhibitors in congestive heart failure

Angiotensin-converting enzyme inhibitors have had a significant impact on the treatment of congestive heart failure (CHF). Hemodynamic and clinical improvements in patients with severe CHF fostered the use of angiotensin-converting enzyme inhibitors in mild to moderate CHF. Angiotensin-converting enzyme inhibitors produce acute and sustained improvements in ventricular hemodynamics and quality of life. Captopril plus diuretic therapy is an effective alternative to digoxin in patients with mild to moderate CHF. Enalapril maleate and lisinopril have been shown to be effective in moderate to severe CHF when combined with digoxin and diuretics. Captopril and enalapril also improve survival in selected patients; captopril attenuates left ventricular dilatation after myocardial infarction. Although all angiotensin-converting enzyme inhibitors are similar in mechanism of action, pharmacokinetic differences impact their clinical use. Prolonged symptomatic hypotension compromising systemic perfusion and organ function has been reported with longer-acting agents; hypotension is usually short-lived and rarely compromises organ function with shorter-acting agents.     

Influence of severity of heart failure on the efficacy of angiotensin-converting enzyme inhibition.

Angiotensin-converting enzyme (ACE) inhibition slowed the progression of congestive heart failure (CHF) in 170 patients who were randomly assigned to either captopril or placebo in the Munich Mild Heart Failure Trial. The two major end points were progression from New York Heart Association (NYHA) functional classes I, II, or III to class IV, despite optimal, adjusted standard therapy, and death due to CHF. The relative risk for progressive CHF with captopril therapy was 0.34 (95% confidence interval = 0.17-0.68; p = 0.01). A total of 52 prerandomization variables were tested to determine their contribution to disease progression. Logistic regression analysis revealed 5 independent risk factors for progressive CHF: NYHA class, left ventricular end-systolic diameter, need for diuretic, age, and cardiothoracic ratio. The presence of greater than 2 of these risk factors increased the odds ratio for progression to 8.13 (p less than 0.001) compared with the presence of 0-2 risk factors. However, the effectiveness of captopril in preventing progression was higher within the subgroup of patients who had less severe CHF: the odds ratio was 0.12 (95% confidence interval = 0.03-0.45; p less than 0.01) for patients in NYHA class I or II on captopril and was 0.83 for those in class III. We conclude that the severity of CHF, as represented by the above-defined risk factors, is directly related to the likelihood for the development of progressive heart failure. However, the less severe the heart failure, the more effective the treatment with captopril will be in preventing disease progression. Thus, ACE inhibition has considerable potential for improving the prognosis of patients with mild heart failure.     

Effects of captopril on forearm oxygen consumption during dynamic handgrip exercise in patients with congestive heart failure

The maximal exercise capacity of patients with congestive heart failure (CHF) is frequently decreased because of decreased skeletal muscle oxygen utilization. In this study we examined whether forearm oxygen utilization is decreased during dynamic handgrip exercise in patients with CHF and whether captopril improves forearm oxygen utilization. They were divided into 3 groups according to the level of plasma renin activity (PRA) and New York Heart Association functional classification (NYHA): Group 1 consisted of 7 normal (control) subjects (PRA: 0.5 +/- 0.2 ng/ml/h, NYHA: 0); Group 2, 7 patients with severe CHF (PRA: 11.3 +/- 3.9 ng/ml/h, NYHA: 3.6 +/- 0.3); Group 3, 4 patients with mild CHF (PRA: 2.4 +/- 0.2 ng/ml/h, NYHA: 2 +/- 0). Forearm blood flow was measured by a strain gauge plethysmograph at rest and during dynamic handgrip exercise. Regional arterial venous oxygen content was measured and forearm oxygen consumption was calculated by the Fick principle. Forearm blood flow was less (p less than 0.05) at rest and during exercise in patients with severe CHF than in control subjects; this was compensated for by increased oxygen extraction, thus maintaining forearm oxygen consumption at a normal level at rest and during submaximal exercise. During maximal exercise, oxygen extraction was not different between normal control subjects and patients with severe CHF, thus forearm oxygen consumption was significantly less (p less than 0.01) in patients with severe CHF than in control subjects. In patients with mild CHF, forearm blood flow, oxygen extraction and oxygen consumption were not different from those in normal control subjects. Captopril (25 mg orally) did not alter forearm hemodynamics at rest and during exercise in control subjects and patients with mild CHF. In patients with severe CHF, captopril lowered systolic and mean blood pressure (p less than 0.05). Captopril increased forearm oxygen extraction (p less than 0.05) and tended to increase blood flow and thus increased oxygen consumption (p less than 0.01) during maximal exercise. Our data indicate that oxygen utilization was impaired in patients with severe CHF and that captopril improved forearm oxygen utilization during maximal handgrip exercise in patients with severe CHF.     

Captopril and the diuretic requirements in moderate and severe chronic heart failure

The effect of captopril on diuretic requirements was assessedin 16 patients with moderate (13 NY HA Class III, 1 NY HA ClassII) or severe (3NYHA Class IV) stable non-oedematous chronicheart failure. The dose of diuretics was halved before captoprilwas started and follow-up was continued for two months. In allthree patients in NYHA Class IV the diuretic dosage had to beincreased to a dose close to, or the same as, the original doseof diuretics in order to keep them from congestive heart failure.One patient improved on the new regime but gained 3·5kg in weight during follow-up. Of the 13 patients with moderateheart failure, seven showed an improvement in symptoms and exerciseduration on the combination of captopril and the lower doseof diuretics (mean 6·9 to 12·5 min, P0·001);two patients did not improve and gained 1·7 kg and 2·3kg in weight, respectively; three patients required the originaldose of diuretics to keep them from congestive heart failureand one patient lost weight on the reduced dose of diureticsbut showed no improvement clinically or on treadmill exercisetesting. Thus captopril does not have a diuretic sparing effectin patients with severe chronic heart failure. Those treatedneed the original dose of diuretics for maximal symptomaticbenefit. Captopril does have a diuretic sparing effect in somepatients with moderate chronic heart failure.     

Effect of cardiac resynchronization therapy-defibrillator implantation on health status in patients with mild versus moderate symptoms of heart failure

Indications for cardiac resynchronization therapy (CRT) have expanded to include patients with mild congestive heart failure (CHF) symptoms (New York Heart Association [NYHA] functional class II) because of a demonstrated morbidity reduction in this subset of patients. However, little is known about postimplantation changes in their self-reported health status compared to patients with more severe CHF. The aim of this study was to examine the influence of baseline NYHA functional class on health status changes in the first 12 months after implantation of a CRT with defibrillator (CRT-D). Patients with first-time CRT-D (n = 169, 75% men, mean age 62.1 ± 10.7 years) were recruited from 3 Dutch hospitals. All patients completed the SF-36 Health Survey at the time of implantation and at 12 months after implantation. Mildly (NYHA functional class II; n = 54) and moderately (NYHA functional class III; n = 115) symptomatic CHF patients showed improved health status in several SF-36 domains at 12 months after CRT-D. When adjusting for baseline health status, the groups did not differ with respect to their health status improvement over time, but after adjustment for demographic and clinical factors, the mildly symptomatic patients reported relatively more improvement in general health (B = 10.15, SE = 3.31, p = 0.003) and social functioning (B = 10.64, SE = 3.74, p = 0.005). In conclusion, NYHA functional class II patients reported equal, and in some domains even more, improvement in health status compared to NYHA functional class III patients at 12 months after CRT-D. Hence, CRT not only prevents clinical adverse events in patients with mild CHF symptoms but also improves health status.     

Comparison of different methods of functional evaluation in patients with chronic heart failure

BACKGROUND: Stratification of the severity of heart failure has major prognostic and therapeutic implications. AIMS: To prospectively compare different methods of assessment of functional capacity in patients with chronic heart failure (CHF). METHODS AND RESULTS: We studied 143 patients (78 male and 65 female) with CHF aged less than 70 years (mean 57.3 years). Functional assessment was made clinically according to NYHA classification and according to the Goldman Activity Scale Classification (GASC). Cardiovascular performance was measured by peak O(2) consumption (pVO(2)) and anaerobic threshold (AT) at cardiopulmonary exercise test and by the distance walked during a 6-min walk test (6-MWT). Clinical scales resulted significantly related. Peak VO(2) and AT showed a mild relation with distance covered at 6-MWT (r=0.56 and r=0.46, respectively). Concordance between NYHA classification and levels of performance at cardiopulmonary exercise test or at 6-MWT was less than 50%. CONCLUSION: Our results suggest that none of the usually employed methods give a definitive assessment of functional capacity of cardiovascular system and a high degree of discordance exists among the results of different tests in the same patient. Although NYHA classification maintains its value in clinical evaluation of patients with CHF, the 6-min walk test is recommended in patients with mild-to-moderate CHF (II-III NYHA classes) as a simple and useful screening test to select patients for further diagnostic evaluation.     

Review of randomized trials of digoxin therapy in patients with chronic heart failure.

Although digitalis glycosides were introduced in the treatment of cardiac maladies greater than 200 years ago, controversy persists regarding the precise role of digoxin in any multidrug approach to the treatment of congestive heart failure (CHF). Despite its widespread use for more than 2 centuries, only recently have double-blind, randomized, placebo-controlled trials of digoxin therapy been conducted in patients with moderate CHF and sinus rhythm. These trials demonstrate that digoxin is superior to placebo in improving left ventricular (LV) ejection fraction, increasing exercise capacity, and preventing CHF worsening. Digoxin produces benefits similar to those seen with angiotensin converting enzyme (ACE) inhibitors with regard to clinical compensation and improvement in LV function. However, improved survival is demonstrated only in response to ACE inhibitors. The recently completed RADIANCE study addresses the value of combining digoxin with ACE inhibitor therapy in patients with mild-to-moderate CHF. Because increased mortality has been reported with the newer oral inotropic agents, it currently appears that digoxin is the only oral inotropic agent useful in clinical practice in the treatment of CHF. However, the effects of digoxin on mortality in patients with CHF remain unknown. In the large, double-blind, randomized trial conducted by the National Heart, Lung, and Blood Institute, the effects of digoxin on mortality in patients with CHF and already being treated with ACE inhibitors are currently being evaluated. Presently, based on the results of placebo-controlled studies, it appears that digoxin, alone or in combination with ACE inhibitors, is beneficial in patients with any signs or symptoms of CHF due to systolic LV dysfunction.     

Torasemide vs. furosemide in primary care patients with chronic heart failure NYHA II to IV--efficacy and quality of life

BACKGROUND: The hypothesis was that torasemide, due to more predictable pharmacokinetics/pharmacodynamics, induces greater improvements in functional and social limitation than furosemide and reduces the frequency of hospitalisations in primary care patients with chronic heart failure (CHF). PATIENTS AND METHODS: Prospective, randomized, unblinded study in primary care, 237 patients with CHF (NYHA II-IV), all on ACE inhibitors. Randomisation: torasemide (n=122) or furosemide (n=115), treated for 9 months. Endpoints: Clinical efficacy, quality of life, safety, tolerability, hospitalisations. RESULTS: Clinical improvement was observed in both groups, but the trend to improve by at least one NYHA class was significant only in torasemide- (P=0.014), but not in furosemide-treated patients. There were no differences with regard to adverse events and hospitalisation due to CHF. Overall, tolerability (P=0.0001) and improvement in daily restrictions (P=0.0002) were significantly higher, number of mictions at 3, 6 and 12 h after diuretic intake (P<0.001 at all time points) and urgency to urinate (P<0.0001) significantly lower in torasemide- vs. furosemide-treated patients. CONCLUSION: CHF patients treated with torasemide gain a higher benefit in quality of life than furosemide treated patients, due to torasemide's dual effect on both clinical status and social function.     

Comparison of captopril and ibopamine in mild to moderate heart failure.

OBJECTIVE: To determine the effects of ibopamine 100 mg three times daily compared with captopril 25 mg three times daily on exercise capacity in patients with chronic heart failure. DESIGN: A randomised, double blind, parallel group comparison of the addition of ibopamine versus captopril during a period of 24 weeks. SETTING: 26 outpatient cardiology clinics in seven European countries. PATIENTS: 266 patients, with mild to moderate chronic heart failure (New York Heart Association (NYHA) functional class II, 81% and III, 19%) and evidence of an enlarged left ventricle. Patients received concomitant treatment with diuretics and/or digitalis. MAIN OUTCOME MEASURE: Exercise duration after 24 weeks of treatment, compared with baseline. RESULTS: Mean (SD) ejection fraction was 29 (8)% and the baseline exercise duration in the captopril and ibopamine groups 665 (160) and 675 (174) seconds, respectively. At the end of the study, exercise duration had improved in both groups, by 29 seconds in the ibopamine group (P < 0.01), and by 24 seconds in the captopril group (P < 0.05). There was no difference between groups (P = 0.69, 95% confidence interval -22 to 33). NYHA class, signs and symptoms score, and dyspnoea and fatigue index improved equally in both groups. The total number of adverse events was the same in both treatment groups, but gastrointestinal complaints occurred more often in the ibopamine group. The number of patients with premature withdrawals was no different. CONCLUSIONS: No difference was detected between the effect of captopril and ibopamine on exercise time in patients with mild to moderate heart failure during a treatment period of 24 weeks.     

L-arginine supplementation prolongs exercise capacity in congestive heart failure

BACKGROUND: In congestive heart failure (CHF), endothelial dysfunction may contribute to impairment of exercise induced vasodilatation and decreased exercise capacity. We hypothesised that administration of L-arginine, a precursor of nitric oxide (NO) and postulated antioxidant, may improve endothelium-dependent vasodilatation and exercise capacity and also exert antioxidant activity. AIMS: To investigate the effect of oral supplementation with L-arginine on exercise capacity and markers of oxidative stress in patients with mild to moderate CHF. METHODS: The study had a randomised double-blind cross-over design. Twenty one patients with stable NYHA II-III CHF underwent three exercise tests: initially, after oral administration of L-arginine (9 g/day for 7 days) or placebo. Blood was sampled prior to each test for plasma lipid peroxides, reduced sulphydryl groups and leukocyte oxygen free radical production. RESULTS: We found a higher prolongation of exercise duration time after L-arginine than after placebo (99+/-106 vs 70+/-99 s, p<0.05). There were no significant differences in markers of free radical activity. CONCLUSIONS: In patients with chronic stable CHF, oral supplementation with L-arginine prolongs exercise duration which may be due to NO-induced peripheral vasodilatation. The antioxidant properties of L-arginine have not been confirmed in this ex vivo study.     

Comparison of lisinopril versus digoxin for congestive heart failure during maintenance diuretic therapy. The Lisinopril-Digoxin Study Group.

Lisinopril 5-20 mg once daily was compared with digoxin 0.125-0.375 mg once daily in a double-blind, randomized, parallel-group study involving 217 patients with mild-to-moderate heart failure (New York Heart Association [NYHA] grades II-III) who were maintained on optimized diuretic therapy. After 6 weeks of treatment, digoxin and lisinopril had increased exercise duration by 18 seconds (p = 0.015) and 32 seconds (p = 0.0007), respectively, versus the baseline run-in period. The difference between treatments was not statistically significant (p = 0.1343). After 12 weeks, digoxin and lisinopril had increased exercise duration by 29 seconds and 51 seconds, respectively. The effect of digoxin compared with the baseline value was not significant but that for lisinopril was (p = 0.0027). The difference between treatments approached statistical significance (p = 0.0813). There was no difference between lisinopril and digoxin with regard to their effects on the frequency of ventricular ectopic counts, couplets, or nonsustained ventricular tachycardia. Blood pressures were not significantly different between treatments, although both systolic and diastolic blood pressure were consistently lower in the lisinopril group throughout randomized treatment. The proportions of patients demonstrating an improvement in NYHA grading were similar for both lisinopril and digoxin. Both treatments had similar effects on the symptoms of heart failure. Both drugs appeared to be equally well tolerated with a similar frequency of adverse events reported for both drugs (30% for lisinopril vs 29% for digoxin). Withdrawals from treatment were of a similar frequency for both treatments.(ABSTRACT TRUNCATED AT 250 WORDS)     

Circulating forms of human atrial natriuretic peptide in patients with congestive heart failure

To elucidate the circulating forms of human atrial natriuretic peptide (hANP) in patients with congestive heart failure (CHF), plasma samples obtained from 36 patients with CHF were analyzed and compared with those from normal subjects. Plasma concentrations of hANP-like immunoreactivity (LI) from normal subjects and patients with mild CHF (class I), as classified by the New York Heart Association (NYHA) functional criteria, did not differ (15 +/- 1 vs. 16 +/- 1 pmol/L, mean +/- SE), whereas plasma levels of hANP-LI in patients with moderate and severe CHF significantly (P less than 0.01) increased in relation to the severity of CHF (class II, 44 +/- 4 pmol/L; class III, 116 +/- 24 pmol/L; class IV, 141 +/- 21 pmol/L). Reverse-phase HPLC and gel permeation chromatography coupled with RIA for hANP revealed that the circulating forms of hANP-LI consisted of alpha-hANP, beta-hANP, and gamma-hANP in CHF, whereas alpha-hANP predominated in normal plasma. The percentage of beta-hANP in total hANP-LI as calculated from the chromatograms by gel filtration was greater in severe CHF (NYHA class III and IV) than those in mild CHF (NYHA class I and II), and apparently exceeded those of other forms. Successful medical treatment for CHF resulted in a marked reduction of total plasma hANP-LI levels with a concomitant disappearance or reduction of beta-hANP in 14 patients examined. These data suggest that beta-hANP and gamma-hANP are secreted from the failing human heart, possibly resulting from the augmented synthesis and/or the altered processing of hANP precursor in cardiocytes, and that circulating beta-hANP may serve as a potential marker for the severity of CHF in man.     

巯甲丙脯酸与螺内酯联合治疗老年人充血性心力衰竭并室性心律失常的临床观察

目的 :研究巯甲丙脯酸与螺内酯联合治疗老年人充血性心力衰竭 (CHF)并发室性心律失常的临床疗效及安全性。方法 :对 2 0 0例老年 CHF并发室性心律失常病例进行临床研究 ,观察其加用巯甲丙脯酸与螺内酯后心功能及临床征象的变化。结果 :用药后 98%病例室性期前收缩明显减少 ,部分有短阵室性心动过速或 Ron T现象 ,用药后消失 ,96 %病例用药后心功能改善 1级以上 (NYHA分级 ) ,临床症状明显好转。全部病例钾离子稳定在正常范围 ,无一例高钾血症发生。结论 :巯甲丙脯酸与螺内酯联合治疗老年 CHF并室性心律失常疗效肯定、可靠、安全性好、副作用少 ,值得推广     

Effects of discontinuing maintenance digoxin therapy in patients with ischemic heart disease and congestive heart failure in sinus rhythm

To evaluate the importance of oral maintenance digoxin therapy in chronic congestive heart failure (CHF), 24 patients in sinus rhythm on maintenance digoxin for documented CHF were studied prospectively on and off the drug. The average duration of therapy was 39 months (range 2 to 180). All 24 patients had documented coronary artery disease (CAD): 22 were in New York Heart Association functional class III and 2 in class II. Twenty-one patients (88%) were receiving diuretic or vasodilator therapy, or both, before digoxin discontinuance. At 1 month off digoxin and with no increase in doses of other medications excepting minor increases in antianginal therapy in 2 patients, no difference was observed in the group as a whole in symptoms, resting heart rate, arterial blood pressure, physical findings, weight, cardiothoracic ratio, radiographic signs of pulmonary congestion, radionuclide left ventricular ejection fraction (LVEF), duration of symptom-limited treadmill exercise (14 patients), or CHF score, compared with evaluation during maintenance digoxin therapy. Similar results were obtained in a subgroup of 9 patients with a resting LVEF < 0.35 (0.27 ± 0.02; mean ± standard error of the mean). Six patients had a decrease and 5 patients an increase in LVEF of ≥0.05 units after cessation of digoxin. Off digoxin, the CHF score increased by only 1 point in 2 patients, but also decreased in 2 patients. Thus, in this study population comprised of patients with CAD with documented CHF, most of whom were receiving diuretics or vasodilators, or both, digoxin withdrawal had no adverse clinical or hemodynamic effects.     

Comparative effects of long-term therapy with captopril and ibopamine in chronic congestive heart failure in old patients

Little is known concerning the long-term drug management of chronic heart failure (CHF) in old patients (greater than or equal to 75 years). Accordingly, this double-blind, placebo-controlled trial compared the long-term (over 6 months) effect of captopril (37.5-75 mg/day) and of ibopamine (150-300 mg/day) on exercise testing, symptoms and subjective feeling of well-being, in 150 CHF elderly patients (mean age 75 years) under treatment with digitalis and/or diuretics. During an additional open follow-up of approximately 1.5 years, morbid events and deaths were also recorded. Captopril and ibopamine performed better (p less than 0.01) than placebo, improving the 6-min walking distance (captopril from 300 to 404 m, ibopamine from 282 to 385 m; placebo from 283 to 299 m). NYHA status, symptom score and patients' global assessment. The difference between the active study drugs was not statistically significant (p greater than 0.05). Complicating events, including diuretic use, frequency of hospitalization, worsening of CHF and deaths, were grouped by patient-years. These events were significantly (p less than 0.01) lower (captopril: 28/75 patient-years; ibopamine 33/74 patient-years) in the active treatment groups with respect to placebo (58/96 patient-years). Captopril and ibopamine showed a different safety profile. Creatinine increase (2 patients), symptomatic hypotension (4 patients), hyperkalemia (2 patients) and upper respiratory symptoms were mostly associated with captopril treatment. Gastrointestinal adverse events were observed in 11 patients under ibopamine treatment. The study provides evidence of the clinical usefulness of both captopril or ibopamine in the long-term treatment of CHF in old patients. The safety profile of each drug will suggest the preferred therapeutic application.     

Differences between cardiologists and internists in the management of heart failure. Medical guidelines compared with every-day practice

BACKGROUND: A marked progress in the treatment of chronic heart failure (CHF) took place during the last decade. Large, randomised studies documented the role of angiotensin-converting enzyme inhibitors (ACE-I) and beta-blockers in the reduction of mortality and morbidity in CHF. AIM: To assess differences in the management of CHF patients between cardiologists and internists. METHODS: Medical records of 433 patients with CHF, aged 38-98 years, hospitalised between October 2000 and May 2002 in an academic centre, were retrospectively analysed. Cardiologists treated 241 patients, and internists - 192 patients. In addition, 12 randomly selected physicians who treated CHF patients, filled-in a questionnaire concerning CHF treatment. Next, the answers were compared with the actual treatment, documented in patients medical files. RESULTS: There were significant differences in the CHF treatment between cardiologists and internists. Cardiologists significantly more often prescribed ACE-I in NYHA class III patients (77% vs 58%, p=0.003), beta-blockers in all NYHA classes (80% vs 57%, p<0.001), loop diuretics in NYHA classes III and IV (76% vs 42%, p<0.001 and 91% vs 44%, p=0.005), and thiazides in NYHA class III patients (36% vs 11%, p<0.001). Internists more often used loop diuretics (37% vs 15%, p<0.001), digoxin (28% vs 7%, p<0.001) and aldosterone antagonists (24% vs 13%, p=0.022) in NYHA class II patients. All cardiologists and almost half of internists declared combined usage of ACE-I and beta-blockers at increasing dosages as the treatment was continued. The highest concordance between declared and actual medication concerned the concomitant use of ACE-I and beta-blockers. CONCLUSIONS: Cardiologists used more often ACE-I and beta-blockers than internists in the treatment of CHF patients. A satisfactory knowledge of treatment guidelines was not associated with widespread usage of ACE-I and beta-blockers in every-day practice.     

西拉普利对充血型心力衰竭的疗效观察

目的ACE抑制剂已经广泛地用于治疗严重充血性心力衰竭,但是用于治疗轻、中度心力衰竭少见报道。本组观察西拉普利对轻、中度心力衰竭的疗效。 方法68例心力衰竭病人,NYHAⅡ～Ⅲ级,观察治疗前后试验组病人症状、体征和运动试验耐受情况,并同安慰剂组进行对照。 结果试验组运动耐受程度改善27%,而安慰剂组仅为5%(\%P\%<0.001);试验组心力衰竭和NYHA分级也明显提高,两组血清钾、肌酐和尿酸无显著差异。 结论西拉普利明显改善轻、中度心力衰竭的症状,提高运动耐量,而且耐受良好。     

Cellular endotoxin desensitization in patients with severe chronic heart failure

BACKGROUND: Increased levels of bacterial lipopolysaccharide (LPS) have been demonstrated in chronic heart failure (CHF). LPS can induce cellular desensitization, with specific down-regulation of LPS-mediated cellular tumor necrosis factor (TNF-alpha) production which does not affect other cytokine parameters. It is not known if LPS desensitization occurs in CHF. METHODS AND RESULTS: Mononuclear cells from 24 CHF patients (mean age 70+/-2 years, age range 58 to 78 years, NYHA class 3.0+/-0.2) and 11 healthy controls (mean age 53+/-3 years, age range 39 to 75 years) were separated from venous blood and cultured for 24 h with LPS (E. coli, 0-10 ng/mL). Culture supernatants were tested for TNF-alpha and interleukin-1 receptor antagonist (IL-1RA). Patients were subgrouped into mild (n=10), moderate (n=5), and severe (n=9) CHF. Independently of age, mononuclear cells from patients with severe heart failure produced less TNF-alpha than controls (p<0.05) and patients with mild (p<0.001) or moderate CHF (p<0.05). IL-1RA release was higher for CHF patients as a group, compared with controls (p<0.05). There was no significant difference in IL-1RA release between CHF patient subgroups. CONCLUSIONS: Mononuclear cells from patients with severe heart failure produce significantly less TNF-alpha than healthy controls or patients with mild to moderate disease. Production of IL-1RA is not affected. This resembles a picture indicative of LPS desensitization occurring in patients with severe CHF.     

Predictors of total mortality and sudden death in mild to moderate heart failure. Captopril-Digoxin Study Group

The relation between baseline clinical variables and subsequent mortality was examined in 295 patients with mild to moderate heart failure who participated in a multicenter trial comparing the effect on treadmill exercise tolerance of captopril, digoxin and placebo given in addition to a diuretic drug. At baseline study, all patients had a left ventricular ejection fraction less than or equal to 40%; 81% were in New York Heart Association functional class II. The etiology of heart failure was ischemic in 62% and nonischemic in 38%. During an average follow-up period of 16 months, 47 patients (16%) died and 24 deaths were classified as sudden. By univariate analysis, left ventricular ejection fraction, ventricular premature beat frequency, couplet frequency, ventricular tachycardia frequency, functional class, treadmill exercise time and nonischemic heart disease were statistically associated with mortality. With multiple logistic regression analysis, left ventricular ejection fraction was identified as the variable most closely associated with total mortality (p = 0.006). Twenty-seven percent of patients with an ejection fraction less than or equal to 20% died compared with 7% with an ejection fraction greater than or equal to 30%. Ventricular tachycardia frequency on Holter monitoring was independently associated with both total mortality (p = 0.008) and sudden death (p = 0.003). Patients with a ventricular tachycardia frequency of greater than 0.088 events/h had a mortality rate of 34% compared with 12% in those without ventricular tachycardia. In the multivariate model, functional class (p = 0.02) and etiology of nonischemic heart disease (p = 0.04) remained as independent predictors of mortality, whereas treadmill exercise duration did not.(ABSTRACT TRUNCATED AT 250 WORDS)