Repair of aortic coarctation in infants.

Fifty-three consecutive infants younger than 2 years underwent coarctation repair. A recoarctation occurred in 11 infants (21%). To determine variables associated with recoarctation, we entered preoperative and operative data into a multivariate stepwise logistic regression analysis. Patient weight was an incremental risk factor for recoarctation instead of age, in contrast to previously published studies. Furthermore, the residual gradient after the operation was a strong incremental risk factor. This risk factor was even more significant when expressed as a ratio of the systolic arm pressure, which takes background hemodynamics into account. Because weight is a more significant risk factor than age, we conclude that deferring operation is indicated only when the infant gains weight. Furthermore, a residual gradient is more important in the hemodynamic setting of a lower systolic arm pressure.

Thromboembolism and mechanical heart valves: a randomized study revisited.

BACKGROUND: This study was designed to revise and substantiate previous inferences, based on short-term follow-up, about differences in the incidence of anticoagulant-related events after heart valve replacement among patients who had been randomly assigned to receive either a Björk-Shiley, Edwards-Duromedics, or Medtronic-Hall mechanical heart valve prosthesis. METHODS: Intermediate-term follow-up to January 1995 was completed in 418 of 419 patients randomized to receive one of three types of heart valve prostheses between January 1982 and January 1987. Median follow-up was 98.5 months. Multivariable analysis in the hazard function domain was performed to identify factors that influenced the incidence of time-related thromboembolism and bleeding. These findings were compared with those made previously after a median follow-up of 37.5 months. RESULTS: No differences were found among the three prostheses in rates of anticoagulant-related hemorrhage. However, the incidence of thromboembolism was higher after mitral valve replacement among patients who had received the Medtronic-Hall prosthesis (linearized rate, 5.4% per patient year; 70% confidence interval, 4.0% to 7.1%), compared with Edwards-Duromedics (1.3%; 70% confidence interval, 0.4% to 3.0%) and Björk-Shiley prostheses (1.2%; 70% confidence interval, 0.6% to 2.2%). CONCLUSIONS: At long-term follow-up, in contrast to the findings at short-term follow-up, patients with either Björk-Shiley or Edwards-Duromedics prostheses had low rates of thromboembolism, whereas higher rates occurred in patients with a Medtronic-Hall prosthesis in the mitral position.

Pharmacokinetics of felodipine after intravenous and chronic oral administration in patients with congestive heart failure.

1. In a randomized, parallel, double-blind study felodipine was administered to 11 and placebo to 12 patients with congestive heart failure. The kinetics of felodipine were studied after acute intravenous administration and after chronic oral treatment for 8 weeks. The relationship between cardiac output and pharmacokinetics was analyzed. The pharmacokinetic data were compared with data from young healthy individuals and hypertensive patients. 2. After oral therapy, significant correlations were found between cardiac output and AUC and systemic bioavailability (F). Furthermore, cardiac output before therapy was also significantly correlated with absorption characteristics. No relationship could be demonstrated between cardiac output and i.v. pharmacokinetics. A comparison of patients with heart failure and young healthy individuals revealed that the AUC was three times higher in heart failure patient, while Vss and the ratio of the AUC of the pyridine metabolite to that of felodipine were similar. Oral clearance was reduced by 50% and the terminal half-life was concomitantly increased. Pharmacokinetic data for felodipine are similar in patients with heart failure to published data from elderly hypertensive patients. 3. An increase in liver blood flow during chronic oral therapy, induced by felodipine itself, appears to explain an increase in bioavailability and thus to higher plasma drug concentrations. Thus, it is advisable to start felodipine treatment at a low dosage in patients with congestive heart failure.

Digoxin-felodipine interaction in patients with congestive heart failure.

A possible interaction between felodipine and digoxin was studied in 23 patients with congestive heart failure before and after 8 weeks treatment with both drugs. A modest, non-significant increase in serum digoxin level 2 h postdose (+15%) was found in the felodipine group (n = 11) compared to placebo (n = 12), with no change in the trough and 6 h postdose levels. There was a bimodal distribution of the observed changes in serum digoxin level 2 h postdose: a significant increase (p less than 0.001) was observed only in patients with a high plasma felodipine level, which may have been caused by changes in the absorption rate in those patients. Changes in the elimination of digoxin after felodipine therapy appeared unlikely, since the trough and 6 h post-dose levels were unchanged. Analysis of the clinical characteristics, haemodynamics and laboratory values revealed no significant differences between the subgroups. The observed increase in serum digoxin warrants monitoring the trough and peak levels digoxin in patients with congestive heart failure who are also being treated with felodipine.

Rates of thromboembolism with three different mechanical heart valve prostheses: randomised study.

In 434 operations for valvular heart disease, patients were randomised to receive Björk-Shiley, Edwards-Duromedics, or Medtronic-Hall mechanical prostheses. At a median follow-up time of 37.5 months there were no differences in hazard of death or non-embolic events. In the first six postoperative months the incidence of thromboembolism was about the same for the three valves. Subsequently, however, the incidence of thromboembolism for the Edwards-Duromedics valve was 3.9 times higher than for the Björk-Shiley valve, and for the Medtronic-Hall valve 2.6 times higher than for the Björk-Shiley valve.

Value of New York Heart Association classification, radionuclide ventriculography, and cardiopulmonary exercise tests for selection of patients for congestive heart failure studies.

To evaluate the necessity of an objective cardiopulmonary exercise test in the selection procedure of patients for heart failure studies, 50 patients with congestive heart failure New York Heart Association (NYHA) class II and III and a left ventricular ejection fraction less than 40% were subjected to a cardiopulmonary exercise test. The results of the exercise test were compared with the independent clinical estimation of NYHA class and data of measurements obtained at rest. The NYHA classification separated the patients with a mild to moderate impairment of aerobic capacity from patients with a moderate to severe impairment of aerobic capacity very well, but 32% of the NYHA class II patients had a near normal aerobic capacity, and 29% of the NYHA class III patients had a very severe impairment of aerobic capacity, more compatible with NYHA class IV. Only data from exercise measurements showed differences between groups. The determination of maximal aerobic capacity for an objective assessment of patients' performance at exercise is necessary for a proper selection procedure of patients for heart failure studies.

Different results in cardiopulmonary exercise tests after long-term treatment with felodipine and enalapril in patients with congestive heart failure due to ischaemic heart disease.

We evaluated the cardiopulmonary exercise test results before and after long-term (16 weeks) treatment with the dihydropyridine calcium antagonist, felodipine (10 mg b.i.d., n = 9), and the ACE inhibitor, enalapril (10 mg b.i.d., n = 11), in 20 patients with New York Heart Association class III congestive heart failure. There were no significant differences at baseline. After 16 weeks patients in the enalapril group showed a significant increase in exercise duration and VO2max, without changes in arterial pressures and heart rate. In the felodipine group, exercise duration and VO2max did not change significantly, but arterial pressures and heart rate were significantly reduced at all exercise levels. Between group analysis showed a significant reduction in arterial pressures and heart rate in the felodipine group compared with enalapril, but no differences in aerobic capacity and exercise duration. These results demonstrate that felodipine and enalapril have essentially different effects on cardiopulmonary exercise results in patients with congestive heart failure.

Efficacy of felodipine in congestive heart failure.

The efficacy of felodipine, a vasodilating calcium antagonist, was analysed in 23 patients with congestive heart failure, New York Heart Association class III, during an 8-week, double-blind, randomized, placebo-controlled, parallel study. After felodipine, exercise duration increased significantly without changes in oxygen consumption. Heart rate, arterial pressures and rate pressure product decreased at similar submaximal exercise levels. Invasive haemodynamics before and after 8 weeks of therapy revealed arterial vasodilation without reflex tachycardia and no significant reduction in right atrial, pulmonary and capillary wedge pressures. Subjective symptom scores improved and side-effects were minor. Fluid retention, as assessed by body weight and ankle circumference did not occur. Felodipine has a beneficial effect in patients with moderately severe heart failure. Further research is necessary to demonstrate its long-term efficacy and safety.

Plasma concentration-effect relationship of felodipine intravenously in patients with congestive heart failure.

The pharmacodynamics of felodipine were analyzed in patients with congestive heart failure in a randomized, double-blind, placebo-controlled study. Felodipine at a dose of 1 mg (n = 11) or placebo (n = 12) was given intravenously during a 60-min period. Hemodynamic measurements and plasma samples were obtained every 15 min during a 2-hour period. An increase in heart rate (HR, +8%, p less than 0.01) and cardiac output (CO, +36%, p less than 0.001), and a decrease in mean arterial pressure (MAP, -24%, p less than 0.001) and systemic vascular resistance (SVR, -46%, p less than 0.001), were found. Pulmonary artery, right atrial, wedge pressure, and stroke-work index did not change. Linear regression analysis showed a significant correlation between felodipine plasma levels and changes in HR (r = 0.71, p less than 0.05), MAP (r = 0.94, p less than 0.01), CO (r = 0.73, p less than 0.05), and SVR (r = 0.88, p less than 0.01). A strong hyperbolic correlation was demonstrated between individual plasma levels and changes in MAP (r = 0.97, p less than 0.001). Hysteresis analysis showed that plasma levels are directly related to the concentration at the receptor site. A clockwise hysteresis was found in HR, CO, and SVR, but not in MAP. It is concluded that changes in flow and resistance are based on a physiological adjustment, a baroreflex-mediated response to vasodilation induced by felodipine, resulting in MAPs that remain closely related to felodipine plasma levels over a wide range.