Effects of L-NAME on coronary blood flow, infarct size and the extent of the no-reflow phenomenon.

BACKGROUND: NOS inhibitors are a potential treatment for patients with cardiogenic shock during acute myocardial infarction. Despite hemodynamic efficacy, their effects on the extent of myocardial infarction (MI) and the no-reflow phenomenon (NRP) have not been clarified. METHODS: Sixteen pigs underwent occlusion of the mid left anterior descending coronary artery for 1h followed by reperfusion for 2h. Coronary blood flow (CBF), distal to the occlusion site, was measured. In eight experiments, L-NAME (non selective NO synthetase inhibitor) administration began 10 min before the onset of reperfusion and continued for 2h (loading dose 1mg/kg, perfusion rate: 1mg/kg/h) (L-NAME group). Eight pigs received similarly normal saline (controls). At the end of each experiment, the myocardial area at risk (MAR) and extent of MI and NRP were measured. RESULTS: Hemodynamics at baseline and during ischemia were similar in both groups. During reperfusion, the mean aortic blood pressure was significantly higher in the l-NAME group. In both groups, CBF reached a peak at 5 min of reperfusion, (no difference between groups). CBF gradually returned to baseline levels within 60 min of reperfusion in both groups. No statistically significant differences in the extent of the NRP (51.8 ± 19.7 vs 60.9 ± 11.4 p=0.35) and MI (77.9 ± 13.9 vs 77.1 ± 8.8 p=0.92), both expressed as a percentage of MAR, were observed between the L-NAME group and the control group. CONCLUSIONS: L-NAME administration started immediately before and maintained throughout reperfusion has no effect on NRP and MI size. L-NAME might stabilize patients with post-MI cardiogenic shock without adverse effects on infarct size.

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.

Early heart rate recovery after exercise predicts mortality in patients with chronic heart failure.

BACKGROUND: Patients with chronic heart failure (CHF) have multiple abnormalities of autonomic regulation that have been associated to their high mortality rate. Heart rate recovery immediately after exercise is an index of parasympathetic activity, but its prognostic role in CHF patients has not been determined yet. METHODS: Ninety-two stable CHF patients (83M/9F, mean age: 51+/-12 years) performed an incremental symptom-limited cardiopulmonary exercise testing. Measurements included peak O2 uptake (VO2p), ventilatory response to exercise (VE/VCO2 slope), the first-degree slope of VO2 for the 1st minute of recovery (VO2/t-slope), heart rate recovery [(HRR1, bpm): HR difference from peak to 1 min after exercise] and chronotropic response to exercise [%chronotropic reserve (CR, %)=(peak HR-resting HR/220-age-resting HR)x100]. Left ventricular ejection fraction (LVEF, %) was also measured by radionuclide ventriculography. RESULTS: Fatal events occurred in 24 patients (26%) during 21+/-6 months of follow-up. HRR1 was lower in non-survivors (11.4+/-6.4 vs. 20.4+/-8.1; p<0.001). All cause-mortality rate was 65% in patients with HRR112 bpm (log-rank: 32.6; p<0.001). By multivariate survival analysis, HRR1 resulted as an independent predictor of mortality (chi2=19.2; odds ratio: 0.87; p<0.001) after adjustment for LVEF, VO2p, VE/VCO2 slope, CR and VO2/t-slope. In a subgroup of patients with intermediate exercise capacity (VO2p: 10-18, ml/kg/min), HRR1 was a strong predictor of mortality (chi2: 14.3; odds ratio: 0.8; p<0.001). CONCLUSIONS: Early heart rate recovery is an independent prognostic risk indicator in CHF patients and could be used in CHF risk stratification.

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).

Hemodynamic effects of levosimendan added to dobutamine in patients with decompensated advanced heart failure refractory to dobutamine alone.

A 24-hour infusion of levosimendan was added to dobutamine in 18 patients (aged 63 +/- 9 years) hospitalized for management of decompensated New York Heart Association functional class IV heart failure refractory to a continuous 24-hour infusion of dobutamine (10 microg/kg/min) and furosemide (10 mg/hour); the primary study end point was a >or=40% increase in cardiac index and a >or=25% decrease in pulmonary capillary wedge pressure compared with pretreatment measurements. The primary end point was reached in one of the patients treated with dobutamine alone versus 7 patients (39%) treated with levosimendan and dobutamine combined (p = 0.008), whereas at 24 hours, the combined treatment was associated with a 0.76 +/- 0.78 L/min/m(2) (p = 0.001) mean increase in cardiac index and a 6.4 +/- 7.3 mm Hg (p = 0.002) mean decrease in pulmonary capillary wedge pressure compared with measurements obtained after 24 hours of dobutamine infusion alone. Symptoms were alleviated in all patients, and all but 3 were discharged from the hospital.