Outpatient management program of patients with chronic heart failure

Hospitalization of patients with heart failure is often caused by poor adherence to drug therapy, by suboptimal utilization of ACE inhibitors and beta-blockers, and by the lack of systematic monitoring of patients after discharge. The aim of the study is to verify the impact of an outpatient management program on the hospitalization rate and functional status of patients with chronic heart failure. Over a five-year period, 435 patients entered our outpatient management program, which includes adjustment in medical therapy, patient education and visits timed according to the patient's status. Fifty-six percent of the patients were in New York Heart functional class I-II; 74% were male; mean age was 62 +/- 11 years. Heart failure was due to coronary heart disease in 42%, dilated cardiomyopathy in 35%, hypertensive heart disease in 13%, other etiologies in 10%. The following changes in medical therapy were made compared to the period before referral: ACE inhibitors in 88% of the patients vs 70% (p < 0.05), mean dose of enalapril and captopril respectively 18 +/- 6 mg vs 11 +/- 4 mg (p < 0.05) and 89 +/- 28 mg vs 61 +/- 34 mg (p < 0.05); digoxin in 71 vs 70% (NS); furosemide in 90 vs 87%; beta-blockers in 16 vs 6% (p < 0.05); amiodarone in 24 vs 16% (p < 0.05); oral anticoagulants in 22 vs 12% (p < 0.05); calcium channel blockers in 10 vs 16% (p < 0.05). During the follow-up period (35 +/- 11 months), there were 111 hospital admissions compared to 518 during the year before recruitment (p < 0.05). Seventy-two patients died (65 for cardiac causes) and four patients underwent cardiac transplantation. Functional status improved (301 patients in I-II functional class and 56 in III-IV after referral compared to 225 and 132 before referral, respectively). Our results were obtained through adjustment in pharmacological therapy, intensive patient education and therapeutic continuity made possible by our outpatient heart-failure clinic organization. It is likely that the increase in costs due to therapeutic adjustment and to the increase in the number of visits is counterbalanced by the reduced rate of hospital admissions.     

Relation of daily activity levels in patients with chronic heart failure to long-term prognosis

Symptom-limited, laboratory-based exercise tests are often used to define prognosis in patients with chronic heart failure, but they do not relate to measures of normal daily activity. Invasive measures of central hemodynamics similarly relate poorly to outcome. Pedometer scores of weekly walking are markedly reduced in patients with heart failure, but whether this less artificial measure of exercise capacity is important in predicting prognosis is not known. Eighty-four patients with chronic heart failure were followed for a mean of 710 days during which 44 died and 3 underwent cardiac transplantation. Symptom-limited treadmill exercise capacity using 2 different protocols did not predict survival, whereas reduced weekly pedometer scores were strong predictors of death (p < 0.001). Other variables that predicted death included resting cardiac output, arterial blood pressure, diuretic requirements, New York Heart Association class, increased bilirubin, and hyponatremia (all p < 0.01). Reduced levels of daily activity are strong predictors of death in chronic heart failure and appear more powerful than laboratory-based exercise tests. This type of assessment is valuable in identifying patients at high risk and provides an objective measure of incapacity during normal daily life. The exercise capacity of patients unable to exercise in the laboratory could also be assessed using this technique. This may prove invaluable in clinical and mortality trials.     

Impaired heart rate variability in patients with symptomatic NYHA class II-III hypertrophic cardiomyopathy

Power spectral analysis of heart rate variability was performed to assess cardiac autonomic function using Holter monitoring in 19 hospitalized patients with symptomatic NYHA class II-III hypertrophic cardiomyopathy (sHCM), 20 ambulatory patients with asymptomatic NYHA class I hypertrophic cardiomyopathy (asHCM) and 20 normal control subjects. Power spectral analysis decomposed the heart rate variability into high-frequency power (HF: 0.15-0.40 Hz) and low-frequency power (LF: 0.04-0.15 Hz). HF was corrected by mean RR intervals (CCVHF). CCVHF values and LF/HF ratios were used as indices of vagal and sympathetic modulations, respectively. The sHCM group demonstrated no significant elevation in CCVHF during the nighttime as compared to the daytime, while asHCM and control groups showed significant CCVHF elevation during the nighttime (p < 0.05-0.01). The nighttime CCVHF, therefore, was significantly lower in the sHCM group than in the control or asHCM group (sHCM, 1.08 +/- 0.36%; control, 1.60 +/- 0.57%; asHCM 1.82 +/- 0.77%; sHCM vs. control or sHCM vs. asHCM, p < 0.01). All of these three groups showed significant reduction in LF/HF ratio during the nighttime as compared to the daytime (p < 0.01). However, the reduction in the sHCM group was not as great as that in the control group and there was a significant difference between the sHCM and control group (2.01 +/- 1.58 vs. 1.08 +/- 0.65, p < 0.05). Two patients in the sHCM group, who later died suddenly, demonstrated very low CCVHF throughout a 24-hour period (0.2-0.8%). Both vagal and sympathetic impairment with a predominance of vagal abnormalities is suggested in patients with symptomatic NYHA class II or III hypertrophic cardiomyopathy.     

Cytokine generation capacities of monocytes are reduced in patients with severe heart failure

BACKGROUND: Immunologic mechanisms mediated by proinflammatory cytokines have been implicated in the pathogenesis of heart failure. Although monocytes are the major source of such cytokines, little is known about their cytokine generation capacities in heart failure. METHODS: We measured plasma levels of 7 major monocyte-related cytokines and the generation capacity of monocytes for 3 cytokines (interleukin-1alpha, interleukin-1beta, and tumor necrosis factor-alpha) on stimulation by lipopolysaccharide in 45 consecutive patients with heart failure and 27 controls. The cytokine levels were measured by enzyme-linked immunosorbent assay. RESULTS: The generation capacities of monocytes for all 3 cytokines were decreased in patients with worsened outcome during hospitalization and the monocyte capacities were significantly reduced in patients with severe heart failure (New York Heart Association class IV). There was a significant negative correlation between the cytokine generation capacities of monocytes and the plasma cortisol levels. Moreover, cortisol significantly inhibited the cytokine production by lipopolysaccharide-stimulated monocytes ex vivo. CONCLUSIONS: These results indicate that the cytokine generation capacities of monocytes are reduced in patients with severe heart failure, partly because of the negative regulation by cortisol. Because monocytes and cytokines play a central role in immune responses, this reduced monocyte function may be involved in part in the pathophysiology of severe heart failure.     

Results of atrioventricular synchronous pacing with optimized delay in patients with severe congestive heart failure

To verify that atrioventricular (AV) synchronous pacing (DDD) with short AV delay improves the condition of patients with severe congestive heart failure, we implanted DDD pacemakers in 10 patients with severe heart failure (New York Heart Association [NYHA] class III to IV). One day after pacemaker implantation, the AV delay was optimized by Doppler echocardiographic measurements over the aortic outflow tract. Patients were evaluated regarding NYHA class, stroke volume, cardiac output, ejection fraction, and quality of life at 1, 3, and 6 months after pacemaker implantation. Although the optimized AV delay was associated with short-term improvement in stroke volume and cardiac output (baseline stroke volume = 22 +/- 7 ml, day 1 = 28 +/- 12 ml; p = 0.03: baseline cardiac output = 1.9 +/- 0.6 L/min, day 1 = 2.2 +/- 1.1 L/min; p = 0.10), the mean stroke volume, cardiac output, NYHA class, and ejection fraction did not change significantly after 1, 3, and 6 months of pacing compared with baseline values. Three patients improved in NYHA class during the follow-up. A consistent improvement in stroke volume, cardiac output, NYHA class, and ejection fraction was observed in only 1 patient. In conclusion, we found no beneficial effects of AV-synchronous pacing with optimized AV delay in patients with severe heart failure.     

Evaluation of a new bipyridine inotropic agent--milrinone--in patients with severe congestive heart failure

Milrinone, a derivative of amrinone, has nearly 20 times the inotropic potency of the parent compound and does not cause fever or thrombocytopenia in normal volunteers or in animals sensitive to amrinone. In 20 patients with severe congestive heart failure, intravenous milrinone resulted in significant decreases in left ventricular end-diastolic pressure (from 27 +/- 2 to 18 +/- 2 mm Hg), pulmonary wedge pressure, right atrial pressure, and systemic vascular resistance, as well as a slight reduction in mean arterial pressure. Significant increases occurred in cardiac index (from 1.9 +/- 0.1 to 2.9 +/- 0.2 liters per minute per square meter) and the peak positive first derivative of left ventricular pressure, with a slight increase in heart rate. Hemodynamic improvement was sustained during a 24-hour continuous infusion. Nineteen of the 20 patients subsequently received oral milrinone (29 +/- 2 mg per day) for up to 11 months (mean, 6.0 +/- 0.8), with sustained improvement in symptoms of heart failure. In 10 patients receiving long-term oral milrinone (greater than or equal to 6 months) radionuclide ventriculography showed continued responsiveness, with a 27 per cent increase in left ventricular ejection fraction after 7.5 mg of the drug. Four patients died after a mean of 4.8 months of therapy, and three patients with severe underlying coronary-artery disease and angina pectoris required additional antianginal therapy. No patient had fever, thrombocytopenia, gastrointestinal intolerance, or aggravation of ventricular ectopy. We conclude that milrinone shows promise for the longterm treatment of congestive heart failure.     

Short-term oral endothelin-receptor antagonist therapy in conventionally treated patients with symptomatic severe chronic heart failure

BACKGROUND: The vasoconstrictor peptide endothelin-1 (ET-1) is important for increased vascular tone in patients with chronic heart failure, but the effects of endothelin-receptor blockade in addition to conventional triple therapy are unknown. METHODS AND RESULTS: Thirty-six men (mean age+/-SD, 55+/-8 years) with symptomatic heart failure (NYHA class III; left ventricular ejection fraction, 22.4+/-4.5%) despite treatment with diuretics, digoxin, and ACE inhibitors received, in a double-blind and randomized fashion, either additional oral bosentan (1.0 g BID; n=24) or placebo (n=12) over 2 weeks. Hemodynamic and hormonal (plasma ET-1, norepinephrine, renin activity, and angiotensin II) measurements were obtained before and repeatedly for 24 hours after administration of bosentan on days 1 and 14. Bosentan was discontinued in 1 patient with symptomatic hypotension, and 2 patients (bosentan group) declined hemodynamic investigations on day 14. Compared with placebo, bosentan on day 1 significantly decreased mean arterial pressure (difference from baseline over 12 hours [95% CIs], -13.9% [-16.0% to -11.7%]), pulmonary artery mean (-12.9% [-17. 4% to -8.3%]) and capillary wedge (-14.5% [-20.5% to -8.5%]) pressures, and right atrial pressure (-20.2% [-29.4% to -11.0%]). Cardiac output increased (15.1% [10.7% to 19.7%]), but heart rate was unchanged. Both systemic (-24.2% [-28.1% to -20.3%]) and pulmonary (-19.9% [-28.4% to -11.4%]) vascular resistance were reduced. After 2 weeks, cardiac output had further increased (by 15. 2% [10.8% to 19.6%]) and systemic (-9.3% [-12.3% to -6.4%]) and pulmonary (-9.7% [-16.3% to -3.1%]) vascular resistances further decreased compared with day 1. Heart rate remained unchanged. Plasma ET-1 levels increased after bosentan, but baseline levels of the other hormones were unchanged. CONCLUSIONS: Additional short-term oral endothelin-receptor antagonist therapy improved systemic and pulmonary hemodynamics in heart failure patients who were symptomatic with standard triple-drug therapy. Further investigations are warranted to characterize the effects of long-term endothelin-receptor antagonist therapy on symptoms, morbidity, and mortality in such patients.     

The current role of amiodarone in patients with congestive heart failure

Amiodarone in low to moderate doses is generally safe in controlling arrhythmias in patients with congestive heart failure (CHF). However, its role is uncertain, because it did not affect the overall mortality rate in three out of four large-scale studies. Whether some subgroups might benefit is a matter of speculation. In patients with sustained ventricular tachycardia, or in those who have survived an episode of sudden death, implantation of a cardioverter-defibrillator may be a better strategy.     

A dose-dependent increase in mortality with vesnarinone among patients with severe heart failure. Vesnarinone Trial Investigators

BACKGROUND: Vesnarinone, an inotropic drug, was shown in a short-term placebo-controlled trial to improve survival markedly in patients with severe heart failure when given at a dose of 60 mg per day, but there was a trend toward an adverse effect on survival when the dose was 120 mg per day. In a longer-term study, we evaluated the effects of daily doses of 60 mg or 30 mg of vesnarinone, as compared with placebo, on mortality and morbidity. METHODS: We enrolled 3833 patients who had symptoms of New York Heart Association class III or IV heart failure and a left ventricular ejection fraction of 30 percent or less despite optimal treatment. The mean follow-up was 286 days. RESULTS: There were significantly fewer deaths in the placebo group (242 deaths, or 18.9 percent) than in the 60-mg vesnarinone group (292 deaths, or 22.9 percent) and longer survival (P=0.02). The increase in mortality with vesnarinone was attributed to an increase in sudden death, presumed to be due to arrhythmia. The quality of life had improved significantly more in the 60-mg vesnarinone group than in the placebo group at 8 weeks (P<0.001) and 16 weeks (P=0.003) after randomization. Trends in mortality and in measures of the quality of life in the 30-mg vesnarinone group were similar to those in the 60-mg group but not significantly different from those in the placebo group. Agranulocytosis occurred in 1.2 percent of the patients given 60 mg of vesnarinone per day and 0.2 percent of those given 30 mg of vesnarinone. CONCLUSIONS: Vesnarinone is associated with a dose-dependent increase in mortality among patients with severe heart failure, an increase that is probably related to an increase in deaths due to arrhythmia. A short-term benefit in terms of the quality of life raises issues about the appropriate therapeutic goal in treating heart failure.     

Inhaled nitric oxide improves exercise capacity in patients with severe heart failure and right ventricular dysfunction

Fourteen cardiac transplant candidates were studied with cardiopulmonary exercise testing at baseline and while breathing nitric oxide (40 ppm). Oxygen consumption at the anaerobic threshold was improved by breathing nitric oxide in patients with pulmonary hypertension and in patients with an elevated left ventricular end-diastolic volume index.     

Value of right ventricular ejection fraction in predicting short-term prognosis of patients with severe chronic heart failure

BACKGROUND: The prognosis of chronic heart failure has been studied extensively, but factors predicting short-term outcome in patients with severe chronic heart failure are still poorly defined, and the current indications for heart transplantation as a treatment for end-stage heart failure need on objective analysis. METHODS: Purpose of the study was to identify the determinants of short-term prognosis in a group of 142 consecutive ambulatory patients (mean age 49.8 +/- 11 years). Referred for heart transplantation because of severe chronic heart failure, the patients were admitted with left ventricular ejection fraction markedly depressed and had had symptoms in spite of an optimal standardized medical therapy for at least 1 month. Baseline clinical and instrumental evaluation included right-sided heart catheterization with a flow-directed multilumen thermodilution catheter, which enables determination of pressures, cardiac output, right ventricular volumes, and ejection fraction. RESULTS: Most patients were in New York Heart Association class III (61%) and IV (24%), and the hemodynamic profile was characterized by mean left ventricular ejection fraction of 20.2% +/- 6%, cardiac index of 2.13 +/- 0.6 l/min/m2, pulmonary capillary wedge pressure of 23.1 +/- 11 mm Hg, right atrial pressure of 7.9 +/- 6 mm Hg, right ventricular ejection fraction of 23.2% +/- 12.4%. During a mean follow-up of 11.1 +/- 9.4 months, 33 patients underwent transplantation (23.4%), 41 died (28.8%), and 68 were still alive (47.8%). There was a substantial overlap in left ventricular ejection fraction between patients divided on the basis of outcome, whereas right ventricular ejection fraction was significantly lower in patients who died or underwent transplantation. Cox multivariate analysis showed three independent prognostic variables: cause (p = 0.03), heart failure score (p = 0.001), and right ventricular ejection fraction (p = 0.000). Short-term survival (10 months) was significantly (p = 0.000) different in patients with > or = 24% or < 24% right ventricular ejection fraction. Statistical analysis identified right ventricular ejection fraction as the single variable to be highly correlated with an increased risk of early death. CONCLUSIONS: This study suggests that right ventricular function is a crucial determinant of short-term prognosis in severe chronic heart failure. Statistical analysis identified right ventricular ejection fraction, determined by thermodilution during right-sided heart catheterization, as the single most important predictor of short-term prognosis in a large cohort of patients who had symptoms in spite of a standardized, optimized, multipharmacologic treatment. The variable allows a useful risk stratification in patients with severe chronic heart failure and uniformly depressed left ventricular ejection fraction and provides guidance in the assessment of indications and timing for transplantation.     

Treatment of congestive heart failure with beta-methyldigoxin (lanitop)

Methylated Digoxin preparation--beta-Methyldigoxin (Lanitop) was used in 50 patients with congestive heart failure of different etiology (tablets of 0.3--0.6 mG per day). Its employment proved very effective in the treatment of congestive heart failure. It is not contraindicated to patients with chronic coronary insufficiency with underlying athrosclerotic cardiosclerosis with signs of congestive circulatory insufficiency. Side-effects of beta-Methyldigoxin are mild and noted rather seldom.     

Safety and efficacy of epoprostenol in patients with severe congestive heart failure. Epoprostenol Multicenter Research Group

Patients with advanced heart failure often remain severely symptomatic and have a high mortality rate despite currently available therapy. We studied the safety and efficacy of a new approach to the patient with refractory heart failure: continuous intravenous treatment via a portable infusion pump with epoprostenol (prostacyclin), a potent pulmonary and systemic vasodilator. A group of 33 patients with severe heart failure (64% New York Heart Association class IV and 36% class III) and profound ventricular dysfunction (median left ventricular ejection fraction, 0.15)--despite prior treatment with diuretics (100%), digitalis (91%), angiotensin-converting enzyme inhibitors (85%), and dobutamine (30%)--underwent a baseline 6-minute walk test prior to dose titration with epoprostenol during invasive hemodynamic monitoring. Subjects responding during the dose titration were randomized, on an open basis, to receive either continuous epoprostenol infusion via an indwelling central venous catheter plus conventional therapy or conventional therapy alone for 12 weeks. The initial dose-ranging study with epoprostenol produced a significant decline in systemic and pulmonary vascular resistance and a substantial increase in cardiac index despite a fall in pulmonary capillary wedge pressure. Symptoms related to vasodilation were noted within the first week after randomization to epoprostenol in 9 of 16 patients but resolved with adjustment of the infusion and concomitant medications in all but one subject. Dose adjustments during the chronic epoprostenol infusion were infrequent after the first week and complications related to the drug delivery system were rare. The change in distance walked from baseline to the last available 6-minute walk test was significantly greater in patients who received epoprostenol compared with patients assigned to standard therapy (72 +/- 40 vs -39 +/- 32 m, mean +/- SEM; p = 0.033). Our study suggests that long-term intravenous infusion of epoprostenol is feasible in patients with severe heart failure and our hemodynamic and functional results suggest clinical benefit as well. However, until recent results indicating an adverse effect of epoprostenol on survival are fully evaluated, the role of this drug in the treatment of advanced heart failure will remain uncertain.     

The treatment of ischemic heart disease in patients with chronic kidney failure

An analysis of the initial type of central hemodynamics and the postoperative period in 177 patients aged older than 70 years having calculous cholecystitis has shown that surgical treatment of patients with the normo- and hyperdynamic types of circulation even with concomitant diseases can give positive results. The least favourable regimen of blood circulation proved to be the hypodynamic type characteristic of patients with pronounced disturbances of homeostasis and/or with recent myocardial infarction.