Amiodarone attenuates the proarrhythmic effects of dobutamine in patients with advanced congestive heart failure.

INTRODUCTION: The long-term use of positive inotropic pharmaceuticals in patients suffering from end-stage congestive heart failure (CHF) has been associated with increased mortality, presumed to be due to proarrhythmia. Oral amiodarone combined with intermittent dobutamine infusions (IDI), on the other hand, has been shown to increase survival. This study evaluated the effects of oral amiodarone on the arrhythmias caused by dobutamine in patients with advanced CHF. METHODS: Thirty patients with CHF, in New York Heart Association functional class III or IV despite optimal medical therapy, were treated with weekly 8-h infusions of dobutamine 10 Ig/kg/min. All patients were treated for 1 month with oral amiodarone, 400 mg/day, before initiation of IDI. A 24-h ambulatory electrocardiogram was recorded on the day before dobutamine infusion and repeated the next day, starting with the onset of infusion. RESULTS: The average heart rate on the 24-h ambulatory electrocardiogram was 72 +/- 14 beats/min before vs. 72 +/- 12 beats/min during IDI (p=1.000). Likewise, dobutamine did not increase the frequency of premature ventricular complexes (23 +/- 32 per h before vs. 42 +/- 69 per h during infusion, p=0.131), ventricular couplets (18 +/- 36 per 24 h vs. 17 +/- 28 per 24 h, p=0.859), or the incidence of non-sustained ventricular tachycardia (27% vs. 40%, p=0.383). No patient developed ventricular fibrillation or sustained ventricular tachycardia during or after IDI. CONCLUSIONS: Chronic low-dose oral amiodarone attenuates the proarrhythmic effects of dobutamine, increasing the safety of ambulatory IDI.

Etiology of anemia in patients with advanced heart failure.

OBJECTIVES: We prospectively investigated the causes of anemia in patients with advanced congestive heart failure (CHF). BACKGROUND: Anemia is common in patients with advanced CHF, and its etiology is generally considered to be multifactorial. However, despite its importance, precise information is lacking regarding the prevalence of putative etiologic factors. METHODS: Patients who were hospitalized for decompensated advanced CHF and who were stabilized after their initial treatment underwent evaluation of "clinically significant" anemia, defined as a hemoglobin content <12 g/dl for men and <11.5 g/dl for women. Patients with a serum creatinine concentration >3 mg/dl or patients with concurrent diseases that are known to cause anemia were not included. The initial evaluation included measurements of vitamin B(12), folic acid, thyroid-stimulating hormone, erythropoietin, lactate dehydrogenase, Coombs test, multiple fecal occult tests, and bone marrow aspiration. Patients without diagnosis by these methods underwent red cell mass measurement with (51)Cr assay. RESULTS: The mean age of the 37 patients was 57.9 +/- 10.9 years and mean left ventricular ejection fraction 22.5 +/- 5.9%. Iron deficiency anemia was confirmed by bone marrow aspiration in 27 patients (73%), 2 patients (5.4%) had dilutional anemia, and 1 patient (2.7%) had drug-induced anemia. No specific cause was identified in 7 patients (18.9%) who were considered to have "anemia of chronic disease." Serum ferritin for the iron-deficient patients was not a reliable marker of iron deficiency in this population. CONCLUSIONS: In this group of patients, iron deficiency was the most common cause of anemia. The iron status of patients with end-stage chronic CHF should be thoroughly evaluated and corrected before considering other therapeutic interventions.

Prevalence and prognostic significance of anemia in patients with congestive heart failure treated with standard vs high doses of enalapril.

BACKGROUND: Anemia is common in patients with congestive heart failure (CHF), although its etiology and pathophysiology remain largely unexplained. The purpose of this study was to examine the prognostic significance of a low hematocrit (Hct) in patients with CHF and the possible role of angiotensin-converting enzyme inhibition in anemia development. METHODS: Hct was measured at the time of enrollment of 160 patients with CHF, mean age 56 +/- 12 years, in New York Heart Association (NYHA) functional class 2.6 +/- 0.7 and with left ventricular ejection fraction of 20 +/- 9%. They were randomized to standard (mean: 17.9 +/- 4.3 mg/day) or high (mean: 42 +/- 19.3 mg/day) doses of enalapril. The follow-up duration was 2 years. Cox regression models were used to identify prognostic factors, and correlations among individual variables were tested. RESULTS: Mean baseline Hct was 42.7 +/- 5%. In multivariate analyses, low Hct (p = 0.036), older age (p = 0.022) and low systolic blood pressure (p = 0.032) were independent predictors of death within 2 years. A correlation was found between baseline Hct and NYHA class (Spearman's correlation coefficient: -0.183, p = 0.008). A significant decrease in Hct from 43.2 +/- 4.9% at baseline to 40.7 +/- 4.4% at 2 years was observed in the group treated with high doses of enalapril (p < 0.001). CONCLUSIONS: Low baseline Hct predicted poor 2-year prognosis in patients with CHF. Enalapril administered in high doses increased the incidence of anemia in this population. The underlying pathophysiologic mechanism and effects of maintaining a normal Hct on clinical outcomes remain to be determined.

The long-term survival benefit conferred by intermittent dobutamine infusions and oral amiodarone is greater in patients with idiopathic dilated cardiomyopathy than with ischemic heart disease.

BACKGROUND: Intermittent dobutamine infusions (IDI) combined with oral amiodarone improve the survival of patients with end-stage congestive heart failure (CHF). The purpose of the present study was to evaluate whether the response to long-term treatment with IDI+amiodarone is different in patients with ischemic heart disease (IHD) versus idiopathic dilated cardiomyopathy (IDC). METHODS: The prospective study population consisted of 21 patients with IHD (the IHD Group) and 16 patients with IDC (the IDC Group) who presented with decompensated CHF despite optimal medical therapy, and were successfully weaned from an initial 72-h infusion of dobutamine. They were placed on a regimen of oral amiodarone, 400 mg/day and weekly IDI, 10 microg/kg/min, for 8 h. RESULTS: There were no differences in baseline clinical and hemodynamic characteristics between the 2 groups. The probability of 2-year survival was 44% in the IDC Group versus 5% in the IHD Group (long-rank, P=0.004). Patients with IDC had a 77% relative risk reduction in death from all causes compared to patients with IHD (odd ratio 0.27, 95% confidence interval 0.13 to 0.70, P=0.007). In contrast, no underlying disease-related difference in outcomes was observed in a retrospectively analyzed historical Comparison Group of 29 patients with end stage CHF treated by standard methods. CONCLUSIONS: Patients with end stage CHF due to IDC derived a greater survival benefit from IDI and oral amiodarone than patients with IHD.

Reverse left ventricular remodeling by intermittent dobutamine infusions and amiodarone in end-stage heart failure due to idiopathic dilated cardiomyopathy.

BACKGROUND: The aim of this study was to evaluate the long-term effect of combined intermittent dobutamine infusions (IDI) and oral amiodarone on reverse left ventricular (LV) remodeling and hemodynamics of patients with idiopathic dilated cardiomyopathy (IDC) and end-stage congestive heart failure (CHF). METHODS: This non-randomized, prospective, clinical trial included sixteen consecutive patients suffering from dyspnea for a mean of 76+/-43 months, who presented with acute cardiac decompensation and were weaned from dobutamine therapy after an initial 72-h infusion. They were then placed on a regimen of oral amiodarone, 400 mg/day and weekly IDI, 10 microg/kg/min, for 8 h. The long-term clinical outcomes and the effects of treatment on reverse LV remodeling (echocardiographic parameters) and hemodynamics were evaluated at 3, 6, and 12 months of follow up. RESULTS: A significant degree of reverse LV remodeling, hemodynamic improvements, and survivals >1.5 years were observed in 9 of the 16 patients (56%). In addition, 5 patients (31% of entire cohort) were weaned from IDI after a mean of 61+/-41 weeks, and 4 remained clinically stable for 116+/-66 weeks thereafter. At 12 months of follow-up, LV end-diastolic and end-systolic volume indices had decreased from 231+/-91 to 206+/-80 ml/m2 (P=0.002) and from 137+/-65 to 110+/-50 ml/m2 (P=0.003), respectively, right atrial pressure from 16+/-6 to 5.6+/-4 mm Hg, (P=0.031), and pulmonary capillary wedge pressure from 29+/-4 to 16+/-5.4 mm Hg, P=0.000, while LV ejection fraction had increased from 22+/-6% to 27.3+/-8% (P=0.006). CONCLUSIONS: In end-stage CHF due to IDC, long-term treatment with IDI and oral amiodarone caused reverse LV remodeling, and allowed permanent and successful weaning from IDI in 1/4 of patients.

Efficacy and safety of intermittent, long-term, concomitant dobutamine and levosimendan infusions in severe heart failure refractory to dobutamine alone.

Thirty-six consecutive patients in New York Heart Association functional class IV, who were resistant to 24-hour continuous dobutamine infusion, were treated with continuous infusions of dobutamine 10 microg/kg/min for > or =48 hours (group I, n = 18), followed by weekly intermittent 8-hour infusions or more often if needed. In group II (n = 18), after the initial 24-hour infusion of dobutamine, a 24-hour levosimendan infusion was added followed by biweekly 24-hour infusions. The addition of intermittent levosimendan infusions prolonged the survival of patients with advanced heart failure refractory to intermittent dobutamine infusions (45-day survival rates were 6% and 61% in groups I and II, respectively; p = 0.0002, log-rank test).

Ultrafiltration in the treatment of severe congestive heart failure.

BACKGROUND: Fluid removal remains a fundamental goal in the treatment of congestive heart failure (CHF). Vacuum ultrafiltration, hemodialysis, or a combination of both was used in patients with severe CHF (NYHA class IV), severe edema, and insensitivity to pharmacological treatment with diuretics. METHODS: The aim of the study was to remove the overload fluid in eighteen patients, 13 men and 5 women, aged 38 to 83, with a man age of 66 years with intractable congestive heart failure. All patients were hospitalized because of severe congestive heart failure and did not respond to treatment with intravenous administration of a high dose of diuretics and positive inotropic agents. They thus underwent vacuum ultrafiltration (1 to 27 sessions) while in 4 of them hemodialysis was also performed because of high serum creatinine levels (over 4 mg/dl). Subclavian catheters were used in all patients and arteriovenous fistula was later performed in 2, because of the need for long term treatment. The average fluid removed was 2 L per session and the total fluid removed ranged from 4 to 29 L. RESULTS: Fourteen of the 18 patients (78%) showed significant improvement in their clinical status. Ten patients (56%) had a short term improvement but expired after 7 to 107 days of hospitalization. Four patients (22%) died after only one session of dialysis and 4 patients (22%) recovered after 8 to 23 dialysis sessions and were discharged from hospital. CONCLUSION: The majority of patients with severe chronic CHF which is intractable to conventional therapy including intravenous diuretics and inotropes improve by the use of ultrafiltration. However, a limited proportion of them survive to be discharged from the hospital.

Lowering of furosemide dosage after clinical stabilization in patients with congestive heart failure.

OBJECTIVES: This study was performed to examine the safety of reducing the long-term doses of furosemide administered to patients with congestive heart failure (CHF) stabilized on a standard medical treatment. METHODS AND RESULTS: Twenty-nine patients with advanced CHF were treated with enalapril, digoxin, nitrates, and furosemide, as needed to alleviate their symptoms, and remained clinically stable for at least 3 months on those doses. Subsequently, the daily dose of furosemide was reduced to 1/3 of the previous dose, while the concomitant therapy was unchanged. All patients underwent a thorough clinical evaluation and right-heart catheterization before and 2 months after the furosemide dose reduction. After the treatment optimization the NYHA functional class decreased from 2.3 +/- 0.6 to 1.4 +/- 0.6 (p = 0.000), and the left ventricular ejection fraction increased from 22 +/- 10% to 32 +/- 13%, (p = 0.000). Clinical and haemodynamic evaluation before and after 2 months of treatment with lower furosemide doses showed that 24 of the 29 patients (83%) remained in a stable NYHA functional class and maintained a stable haemodynamic status. In the remaining 5 patients (17%), mean NYHA functional class increased from 1.8 +/- 0.4 to 2.4 +/- 0.6 (p = 0.07), accompanied by a significant increase of the right and left ventricular filling pressures from 4.2 +/- 2.7 to 9.0 +/- 3.0 mm Hg, p = 0.018 and from 8.6 +/- 3.0 to 19.8 +/- 3.6 mm Hg, p = 0.017, respectively. These 5 patients returned to a stable clinical status upon resumption of the prior doses of furosemide. CONCLUSIONS: Most patients with chronic CHF who were clinically stabilized on high doses of furosemide remained stable on a maintenance dose equal to one-third of the dose needed for their stabilization. Patients unable to tolerate the dose reduction regained their previous clinical status following the resumption of the prior diuretic doses.