Search

Introduction: Oxidative stress in the newborn period may cause cell injury and inflammation if the antioxidant capacity is insufficient. To monitor antioxidant and inflammatory activity we examined by in vivo imaging various strains of luciferase reporter mice whose light-emitting properties were regulated by response elements or complete promoters related to oxidative stress and/or inflammation. The aim of this study is to present a model that can monitor genetic activity in vivo during pregnancy and the first 10 days of life., Methods: One mouse strain reports the activity of nuclear factor-kappaB (NF-kappaB) activity, a transcription factor essential for modulating inflammation, apoptosis, differentiation and cell growth. A second mouse strain reports on superoxide dismutase 1-promoter activity. A third strain reports the promoter activity of gamma-glutamylcysteine synthetase, the rate limiting enzyme in glutathione production, and the last strain reports on antioxidant responsive element (ARE)/electrophil responsive element. Wild-type female mice mated with NF-kappaB mice were imaged through pregnancy to monitor intrauterine NF-kappaB activation., Results: Intrauterine NF-kappaB activity increased dramatically from day 17 towards labor. During the first 4 days of life luminescence measured was intense in all mice with distinct strain differences. All strains had high luminescence levels at day 1 and a considerably lower level at day 10., Conclusion: This model allows investigation of the transcriptional regulation of key proteins related to oxidative stress and inflammation in pregnancy and the first days of life. With very little stress to the newborn animals genetic activity can be monitored day by day., ((c) 2007 S. Karger AG, Basel)

Background: Hemodynamic abnormalities have been documented in the chronic fatigue syndrome (CFS), indicating functional disturbances of the autonomic nervous system responsible for cardiovascular regulation. The aim of this study was to investigate autonomic heart rate control during mild orthostatic stress in adolescents with CFS., Methods: A total of 14 CFS patients and 56 healthy controls having equal distribution of age and gender underwent lower body negative pressure (LBNP) of horizontal line 20 mmHg. The RR interval (RRI) was recorded continuously, and spectral power densities were computed in the low-frequency (LF) band (0.04-0.15 Hz) and the high-frequency (HF) band (0.15-0.50 Hz) from segments of 120-second length, using an autoregressive algorithm. In addition, the time-domain indices SDNN, pNN50, and r-MSSD were computed., Results: At rest, CFS had lower RRI than controls (P < 0.05), but indices of variability were similar in the two groups. During LBNP, compared to controls, CFS patients had lower normalized and absolute HF power and r-MSSD (P < 0.05), and higher RRI (P < 0.001), normalized LF power and LF/HF (P < 0.05)., Conclusions: During mild orthostatic stress, adolescents with CFS appear to have enhanced vagal withdrawal, leading to a sympathetic predominance of heart rate control compared to controls. Possible underlying mechanisms include hypovolemia and abnormalities of reflex mechanisms.

Aim: To register chromosomal anomalies, syndromes and extracardiac malformations in patients with Congenital heart defects (CHDs)., Method: Population-based prospective observational study., Results: Of 57 027 live births during 1982-2005, CHDs were detected in 662 (11.6 per 1000), of whom 146 (22%) had associated anomalies. Of these 52 (36%) had chromosomal anomalies (exclusive microdeletions), 26 (18%) genetic syndromes/microdeletions, 1 (0.7%) a teratogenous syndrome and 67 (46%) extracardiac malformations. In perimembraneous ventricular septal defects (VSDs), associated anomalies occurred in 22 of 70 (31%) compared to 27 of 298 (9%) in VSDs located in the muscular part of the septum (p < 0.0001). The prevalence of CHDs with associated disorders increased significantly from the cohort born during 1982-1993 to those born during 1994-2005 (2.0 vs. 3.1 per 1000, respectively; p < 0.0001), mainly caused by an increase of chromosomal trisomies (0.5 vs. 1.1 per 1000; p = 0.026). The percentage of women giving live birth at 35 years of age or more was 7.6% for the period 1982-1993 compared to 13.4% for 1994-2005 (p = 0.001)., Conclusions: Chromosomal anomalies, syndromes and extracardiac malformations occurred in nearly one-fourth of CHD cases. Muscular VSDs had a low prevalence of such conditions. The prevalence of CHDs with chromosomal trisomies increased, and was probably related to an increasing age of women giving birth.

Aims: Our objectives were, first, to study seasonal distribution of perioperative deaths within 30 days after surgery, and late death, in children undergoing surgery for congenitally malformed hearts, and second, to study the causes of late death., Methods: We analysed a retrospective cohort of 1,753 children with congenital cardiac malformations born and undergoing surgery in the period from 1990 through 2002 with a special focus on the causes of late death. The data was obtained from the registry of congenital cardiac malformations at Rikshospitalet, Oslo, and the Norwegian Medical Birth Registry. The mean follow-up from birth was 8.1 years, with a range from zero to 15.2 years., Results: During the period of follow-up, 204 (11.6%) of the children died having undergone previous surgery. Of these 124 (7.1%) died in the perioperative period, and 80 (4.5%) were late deaths. There were 56 late deaths during the 6 coldest months, compared with 24 during the 6 warmest months (p < 0.01). There was no significant seasonal variation in perioperative deaths. Respiratory infection was the most common cause of late death, and occurred in 25 children, of whom 24 died during the 6 coldest months. Of the 8 sudden late deaths, 7 occurred during the 6 coldest months. There was no seasonal variation for the other causes of death., Conclusions: In children undergoing surgery for congenital cardiac malformations in Norway, there is a seasonal variation in late death, with a higher proportion occurring in the coldest months. Death related to respiratory infections predominantly occurs in the winter season, and is the overall most common cause of late death.

Haemodynamic abnormalities have been documented in the chronic fatigue syndrome (CFS), indicating functional disturbances of the autonomic nervous system responsible for cardiovascular control. This study was designed to explore the pathophysiology in adolescent CFS-patients by analysing RR-interval (RRI) variability and diastolic blood pressure (DBP) variability during mild orthostatic stress, using an algorithm which accounts for non-stationary biosignals. A total of 27 adolescents with CFS and 33 healthy control subjects having equal age- and sex distribution underwent 15 min of 20 degrees head-up tilt (HUT). The spectral power densities of RRI and DBP were computed in the low-frequency (LF) band (0.04-0.15 Hz) and the high-frequency (HF) band (0.15-0.4 Hz) using an adaptive autoregressive algorithm to obtain a time-varying spectrum. RMSSD, a time domain index of RRI variability, was also computed. At rest, all indices of variability were similar in the two groups. During tilt, CFS patients had a larger increase in the LF/HF ratio (P

We describe the effect of propranolol in an adolescent with chronic fatigue syndrome and orthostatic intolerance. Our observations suggest that the head-up tilt-test and beta-blocker treatment might be considered in patients with chronic fatigue syndrome and that enhanced sympathetic nervous activity might be part of the underlying pathophysiology.

We treated prospectively 14 patients with Eisenmenger's syndrome, with a mean age of 10 years, ranging from 3 to 18 years. Treatment continued for 12 months, and demonstrated a lasting symptomatic improvement, but no improvement in terms of mean saturation of oxygen over 24 hours. Exercise capacity, as judged by peak uptake of oxygen, worsened in the six patients able to perform a treadmill test. The symptomatic benefit from dual blockage of endothelin receptors in these patients may be due to mechanisms other than selective pulmonary vasodilatation alone.

Hemodynamic dysfunction is documented in chronic fatigue syndrome (CFS). This study was conducted to investigate cardiovascular responses to orthostatic stress in adolescents with CFS, using a novel procedure for tilt-table testing. A total of 27 adolescents with CFS and 33 healthy control subjects with equal age and gender distribution underwent 15 minutes of 20 degrees head-up tilt testing. Heart rate, systolic blood pressure (BP), mean BP, diastolic BP, stroke index, total peripheral resistance index, end-diastolic volume index, and acceleration index were continuously and noninvasively recorded. At rest, patients with CFS had higher total peripheral resistance index values (p<0.01) and lower stroke index and end-diastolic volume index values (p<0.05) than controls. During 20 degrees head-up tilt testing, patients with CFS had greater increases in heart rate, diastolic BP (p<0.001), mean BP (p<0.01), and total peripheral resistance index (p<0.05) than controls and greater decreases in stroke index (p<0.05). Syncope or near syncope was not observed. In conclusion, this study found that adolescents with CFS have significant abnormalities of cardiovascular regulation in response to mild orthostatic stress, differentiating them from healthy controls.

Aim: To measure the difference in lung function between newborns with univentricular hearts and healthy controls and study associations between lung function and pulmonary blood flow and pulmonary vasculature markings., Method: Tidal flow-volume measurements and single occlusion tests were performed before surgery on 25 unsedated spontaneously breathing newborns with univentricular hearts recruited over a 3-year period. Seventy-five healthy control infants were measured. Pulmonary blood flow was graded according to the haemodynamic effect of the echocardiographically defined anatomy of the heart defect. Pulmonary vasculature was graded according to radiological markings., Results: The infants with univentricular hearts had a lower mean tidal volume of 4.7 ml (CI 2.3, 7.2, p < 0.001) (n = 24) and a lower mean compliance of the respiratory system of 12.7 ml/kPa (CI 4.6, 20.8, p = 0.004) (n = 14). Pulmonary blood flow grading was associated with respiratory rate (r = 0.53, p < 0.001), tidal volume (r =-0.48, p < 0.001), compliance (r =-0.55, p < 0.001) and resistance (r =-0.31, p = 0.043). Pulmonary vasculature grading was associated with compliance (r =-0.68, p = 0.006), resistance (r =-0.69, p = 0.007) and the time constant (r =-0.62, p = 0.042)., Conclusion: Newborns with univentricular hearts have reduced tidal volumes and reduced compliance of the respiratory system. The lung function abnormalities are associated with the degree of pulmonary blood flow and pulmonary vasculature markings.

Most children with functionally univentricular hearts nowadays are treated surgically by creating a total cavopulmonary connection. In the resulting Fontan circulation, the venous return and the pulmonary arterial bed are coupled in series, bypassing the heart. This gives the potential for interaction between the abnormal circulation and function of the lungs. In this study, we investigated the pattern of impairment of pulmonary function, and its relation to decreased exercise capacity. We performed spirometry in 33 (85 percent) of 39 eligible Norwegian children, aged from 8 to 16, with a total cavopulmonary connection, along with whole body plethysmography, the carbon monoxide single breath test, and a peak treadmill exercise test. The single breath test showed a mean corrected diffusing capacity of 66.5 percent of predicted, giving a z score of minus 2.88. The mean residual volume measured by whole body plethysmography was 146.8 percent, equivalent to a z score of 2.46, whereas the mean residual volume measured by the single breath test was 102.4 percent of predicted, this being the same as a z score of 0.43. The mean peak treadmill exercise test was 70.0 percent of predicted, equivalent with a z score of minus 3.07. Mean forced vital capacity was 85.7 percent of predicted, the equivalent z score being minus 0.92. Lung function correlated with the peak treadmill exercise test. We have shown, therefore, that children with the Fontan circulation have reduced diffusing capacity, possibly caused by the abnormal circulation through the lungs. The difference between residual volume measured by plethysmography and the single breath test implies trapping of air. The correlation of parameters for lung function with peak consumption of oxygen during exercise indicates that the abnormalities of pulmonary function may affect physical capacity.

Background: After more than a decade of experience with off-pump coronary bypass surgery, still no consensus exists concerning its benefit on clinical outcome compared to the on-pump technique. In this 12-month follow-up, we compare off-pump and on-pump surgery on the appearance of graft patency, myocardial function, and clinical outcome., Methods: One hundred twenty patients were randomized to off-pump or on-pump coronary surgery. Angiography was performed intraoperatively, at 3 and 12 months. Global myocardial function was estimated by magnetic resonance imaging (MRI) preoperatively and 12 months postoperatively, as well as functional class and stress testing., Results: After 12 months internal mammary artery patency was 94% in the off-pump group and 96% in the on-pump group. Vein graft patency was 80% and 87%, respectively. No statistically significant difference between the two groups existed. There were no differences in exercise capacity improvement and attenuation of symptoms between the groups., Conclusions: At 12-months follow-up, off-pump coronary bypass surgery provided the same angiographic graft patency as the on-pump technique. Improvement in functional class and exercise capacity was the same in both groups.

Myocardial dysfunction, hypotension, and increased pulmonary artery pressure are induced by asphyxia in neonates. We sought to define left ventricular (LV) systolic function by measuring longitudinal and radial contraction by strain Doppler echocardiography (SDE) in hypoxemic newborn pigs. Hypoxemia was induced in 11 anesthetized and instrumented newborn pigs by ventilation with 8% O2 in nitrogen. When mean arterial blood pressure (BP) decreased to 15 mm Hg or arterial base excess reached -20 mmol/L or less, the pigs were reoxygenated and ventilated for 150 min. Echocardiography was performed at baseline and during hypoxemia and reoxygenation. Baseline measurements of myocardial peak systolic strain demonstrated normal longitudinal shortening and radial thickening. During hypoxemia, systolic longitudinal shortening in the mid-posterior and septal segments changed to systolic stretching. Peak strain in the mid-lateral and anterior segments decreased but without signs of paradox wall motion. Short-axis peak strain remained positive during hypoxemia, although the amplitude was reduced and delayed with respect to timing. In the newborn pig heart, we found a complex and heterogeneous systolic pattern with distinct regional differences during global hypoxemia. Rapid changes in LV function during hypoxemia and reoxygenation are assessable by SDE, and the results indicate that longitudinal systolic contraction is more vulnerable to hypoxemic changes than radial contraction. To explore the full picture of a global hypoxemic injury, both long- and short-axis functions have to be considered.

Aims: To investigate the role of guidelines in structuring the clinical care for adult patients with congenital heart disease (CHD), and to assess adherence to the guidelines in Europe., Methods and Results: A selected number of current guidelines were chosen pertaining to operative procedures, investigations, and the use of medication ('interventions'). The source for this analysis was the database of the Euro Heart Survey on adult CHD, which contains retrospectively collected data on 4110 patients followed-up for a median of 5.1 years. For each guideline investigated, patients were selected from the database for whom the particular guideline was relevant. The selected cases were classified according to two criteria: was there an indication for the particular intervention and did the intervention take place? In this manner, cases of 'undue treatment' and 'insufficient treatment' were identified. Adherence to guidelines was found to be good in the case of operative procedures and prophylactic drug treatment. However, regarding diagnostic procedures there had been adherence to guidelines in only slightly more than half of the cases., Conclusion: Guidelines have an important role in the actual clinical care of adults with CHD. However, large outcome studies are needed to develop more precise guidelines.

Aims: To describe clinical and demographic characteristics at baseline of a European cohort of adults with congenital heart disease (CHD) and to assess mortality and morbidity in a 5 year follow-up period., Methods and Results: Data collected as part of the Euro Heart Survey on adult CHD was analysed. This entailed information transcribed from the files of 4110 patients diagnosed with one of eight congenital heart conditions ('defects'), who consecutively visited the outpatient clinics of one of the participating centres in 1998. The patients were included retrospectively and followed until the end of 2003 for a median follow-up of 5.1 years. Notwithstanding their overall relatively good functional class and low mortality over the follow-up period, a considerable proportion of the patients had a history of endocarditis, arrhythmias, or vascular events. There were major differences between the eight defects, both in morbidity and regarding specific characteristics. Outcomes were worst in cyanotic defects and in the Fontan circulation, but a considerable proportion of the other patients also suffer from cardiac symptoms. In particular, arrhythmias are common., Conclusion: The spectrum of adult CHD in Europe emerging from this survey is one of a predominantly young population with substantial morbidity but relatively low mortality in a 5 year period.

Oxidative stress is closely related to inflammation, a pathologic process characterized by activation of the transcriptional factor nuclear factor-kappa B (NF-kappaB). We have used transgenic NF-kappaB luciferase reporter mice to assess brain NF-kappaB activity noninvasively in living mice. We have studied NF-kappaB activation in hypoxic mice reoxygenated with either 21% O2 (room air) or 100% O2. Forty-one mice exposed for 2 h to 4% oxygen and then randomized to reoxygenation with pure oxygen or room air were investigated. A control mouse was dedicated to every mouse exposed to hypoxia. In vivo luminescence originated from brain was measured from mice 2 d before hypoxia, and 3 h after reoxygenation. A change in luminescence between the mouse exposed to hypoxia and its control demonstrates an alteration in NF-kappaB activity. Because of high mortality among males, only females were included. Six female mice died. Nineteen female mice were reoxygenated with room air, 16 with pure oxygen. We observed a significantly higher luminescence in the brain of the 100% O2 group versus the 21% O2 group. Our data indicate that brain NF-kappaB activity is increased in mice subjected to 4% oxygen followed by reoxygenation with 100% oxygen. However, when reoxygenation occurs with 21% O2 (room air), no elevation in NF-kappaB activity is observed. Thus, reoxygenation with room air may induce less brain inflammation than reoxygenation with pure oxygen.

Aims: To register mortality and causes of death in patients with congenital heart defects (CHDs)., Methods: Prospective population-based observational study., Results: 553 infants with CHD (1.1% of live born) were observed for 1-22 y (median 10 7/12 y). Sixty-four died (11.6%), of whom 32 (50%) died during the first 4 wk, and 51 (79.7%) during the first year of life. Of the total neonatal deaths in the population (3 per 1000), CHDs occurred in 21.5%. Mortality for children with CHDs was not significantly different between the cohorts born in 1982-1991 and 1992-2002, for either neonatal deaths or deaths later on (p>0.05). Out of 170 patients in whom therapeutic procedures (surgery, catheter interventions) were undertaken, 34 (20%) died. Nine cases (1.6%) died with unrecognized CHDs; seven of these on the first day of life with severe extracardiac malformations. In 50 (78.1%) cases, death was judged to be caused directly or indirectly from the CHD, and in 14 (21.9%) from extracardiac malformations or other conditions., Conclusion: CHDs occur in a substantial number of neonatal deaths. Most deaths are caused by cardiac insufficiency. The mortality rate remained unchanged.

Echocardiography is a valuable tool in the investigation and follow-up of adult patients with congenital heart disease. The majority of these patients have been recognised and treated in childhood, and effective investigations in adult life depend on exact knowledge of the patient history and previous treatments/operations. The major lesions are presented and important echocardiographic features briefly discussed.

We describe an infant with an atrioventricular septal defect and separate valvar orifices for the right and left ventricles, the so-called primum defect, who presented with serious pulmonary hypertension. Treatment with sildenafil was changed to intravenous epoprostenol due to lack of any measurable effects of the initial therapy as shown by echocardiography. The girl died three days after the change in treatment. We suggest that a mismatch between ventilation and perfusion contributed significantly to her death.

Lung function has been associated with mortality after adjusting for other risk factors; however, few studies have adjusted for physical fitness and reported separate analyses according to smoking status. In 1972-1975, spirometry, clinical and physiological parameters were recorded in 1,623 apparently healthy males aged 40-59 yrs. After 26 yrs of follow-up, the current authors investigated the association between baseline lung function and mortality, adjusting for smoking, physical fitness and other potential factors. By 2000, 615 individuals (38%) had died, with 308 (50%) of these deaths from cardiovascular (CV) causes. Forced expiratory volume in one second was a predictor of all-cause mortality (risk ratio (RR) 1.10 per reduction of 10%) after adjusting for smoking, physical fitness, age, systolic blood pressure, body mass index and serum cholesterol. The corresponding multivariate RR was 1.07 for CV causes and 1.34 for respiratory death. In conclusion, in stratified analyses among current and former smokers, forced expiratory volume in one second % predicted was a strong independent predictor of all-cause mortality and respiratory death among current smokers. Forced expiratory volume in one second % predicted was not associated with mortality among never-smokers.

Aim: The objectives of this study were 1) to compare early mortality (first 30 d after surgery) and long-term survival between two cohorts of patients operated on for congenital cardiac defects, and 2) to evaluate the impact of possible changes in early mortality on long-term survival., Methods: 945 patients with congenital cardiac defects, born in 1990-1999 and operated on in the same period were examined in a retrospective cohort study. The patients were divided into three groups: "univentricular cardiac defects", "severe cardiac defects" and "less severe cardiac defects". The study population was divided into two cohorts: group 1 included patients born and operated on in 1990-1994; group 2 included patients born and operated on in 1995-1999. The survival patterns in the two groups were compared., Results: For all patients, except those with univentricular cardiac defects, early mortality (30 d after surgery) was reduced. Among patients with severe cardiac defects, early mortality was reduced from 18.6% in group 1 to 2.9% in group 2. Among patients with less severe cardiac defects, early mortality was reduced from 6.2% to 1.9%. The improved outcome was maintained during the following 5 y. Overall relative risk of death during follow-up was reduced to 0.31 (95% CI: 0.15-0.56) for patients with severe cardiac defects, and to 0.53 (95% CI: 0.31-0.93) for patients with less severe cardiac defects born and operated on in 1995-1999., Conclusion: Early mortality has been substantially reduced in congenital heart defect patients, and corresponds with significantly improved long-term survival.

We describe the prevalence of extra-cardiac anomalies in children with congenital cardiac malformations, and their impact on survival, compared to the outcome in children with the congenital cardiac lesions as the only recognised anomaly. Our population comprises the 3527 children born with congenital cardiac anomalies between 1990 and 1999, and registered at the largest tertiary centre for Paediatric Cardiology in Norway. Extra-cardiac anomalies were found in one-fifth of the population, with Down's syndrome accounting for nearly one-third. Survival improved for children born between 1995 and 1999 compared with those born in the period from 1990 to 1994 for all groups, except for children with additional extra-cardiac anomalies in the absence of Down's syndrome. The results were the same for children undergoing surgical treatment of their cardiac malformation. The survival in children with Down's syndrome improved in comparable fashion to those without extra-cardiac anomalies. Children with extra-cardiac anomalies in the absence of Down's syndrome represent a heterogeneous group, with varying patterns of survival. Survival did not improve in these latter patients during the period of our study.

Patients with congenital heart disease run the risk of overweight and low physical activity. Lifestyle measures are as important in these patients as in the general population. Exercise testing is an effective tool to identify patients in whom exercise may induce arrhythmias or hemodynamic instability but more often to reveal the safety of exercise, which is the conclusion in the majority of these patients. Systematic training programs have only been introduced to small groups of patients with congenital heart disease, and there are only few data on the effects obtained. The studies concluded that the exercise training programs used were safe.

The objective of the study was to assess behavioural and emotional problems, as well as physical capacity, in children and adolescents with congenital cardiac disease. From the database of Paediatric Heart Section, Children's Clinic, Rikshospitalet University Hospital, Oslo, Norway, we identified 430 patients whose parents received questionnaires using the Child Behaviour Check-List. The response rate was 75.8%. In addition, the parents received a questionnaire focusing on special issues with regard to physical activity. Parents of children and adolescents with congenital cardiac diseases reported significantly more behavioural problems than did a reference population and boys were scored higher compared to girls. Analysis showed a significant impact of physical capacity on the score representing total problems, as well as scores for externalising and internalising behaviour. Compared to a reference population, parents of children and adolescents with congenital cardiac disease score their children higher on most scales when rated using the Child Behaviour Check-List. The type of diagnosis did not affect the scores reflecting the total problem. The main factor of impact on behavioural problems was, as evaluated by the parents, the physical capacity of the children.

Background: We report five years' experience with transcatheter closure of defects in the oval fossa at Rikshospitalet University Hospital in Oslo, Norway., Material and Methods: We reviewed the results in 69 patients between 1.3 and 74 years of age (median 5.3), weighing median 20 kg (7.8-109), with pulmonary blood flow 2.40.74 (1.3-4.8) times systemic flow, and median diameter of the defect 18 mm (9-34). The patients were followed clinically for one year., Results: In 69/77 (90%) the defect could be closed. None had a significant residual shunt. One patient showed a very small residual leak after one year. Two children, not yet seen after one year, had a small shunt after one month. The complication rate has been low, and we have not been able to demonstrate any sequelae. The hospital stay is two nights without any convalescence period. The results compare favourably to surgery., Interpretation: The method was efficient and safe in all age and weight groups. The very limited total volume of such procedures indicates they should be centralised and only carried out by a small number of physicians.

Background: Despite successful coronary angioplasty (PTCA), patients may have ischemia after the procedure because of the overall coronary disease and luminal renarrowing at the lesion sites. The aim of this study was to examine the effects of the calcium-channel blocker amlodipine on post-PTCA ischemia., Methods: In a prospective, double-blind design, patients were randomized to receive 10 mg of amlodipine or placebo 2 weeks before angioplasty. Exercise tests and 48-hour ambulatory electrocardiography recordings were performed in 405 patients, 2 weeks before and 2 and 20 weeks (early and late) after PTCA., Results: There were no differences in clinical and angiographic baseline characteristics between the treatment groups. Ischemia and angina were equally distributed before PTCA, and no difference in restenosis was found between the groups at follow-up. The incidence of angina was significantly lower in the amlodipine group compared with the placebo group both early and late after PTCA (P =.04 and.03). Exercise-induced ischemia was reduced by 40% (P =.009) early and 34% (P =.02) late after PTCA in the amlodipine group, and ischemia on ambulatory electrocardiography was reduced by 18% early and 28% late after PTCA compared with placebo (P =.06 and P =.009)., Conclusion: Ischemia and angina occurred after successful PTCA and were significantly reduced by amlodipine.

Background: We investigated the aerobic capacity of 168 adult patients who had undergone successful surgical repair of retralogy of Fallot at the University of Toronto Congenital Cardiac Centre for Adults., Methods: We compared values of peak uptake of oxygen, peak heart rate, forced vital capacity, and forced expiratory volume in 1 second to predicted values for their age groups., Results: The patients who had undergone surgical repair of tetralogy of Fallot demonstrated an overall diminished peak uptake of oxygen, at 51%,and peak heart rate, at 79%, compared to predicted values. No difference in peak aerobic capacity was found according to the initial surgical strategy of palliation or repair., Conclusions: Adult patients who have undergone surgical repair of tetralogy of Fallot have lower peak uptake of oxygen, and peak heart rate, compared to predicted values. The reduction in the peak heart rate may affect their exercise capacity. The peak uptake of oxygen also decreased with increasing age at the time of testing, and the age at surgical repair.

Introduction: The objective of this analysis was to evaluate the health economic benefits of using amlodipine in patients undergoing angioplasty procedures in Canada and Norway., Methods: A decision tree model was constructed to find the total expected cost per patient for a 4-month time period following an initial angioplasty. The model used clinical data from the Coronary Angioplasty Amlodipine Restenosis Study (CAPARES), a prospective, randomized, double blind, placebo-controlled trial conducted to investigate the effects of amlodipine on restenosis and clinical events in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). Outcomes of interest to this analysis included MI, repeat PTCA, CABG, and all-cause mortality. Clinical experts from Canada and Norway were enlisted and a modified Delphi study approach was used to quantify healthcare resources consumed for each clinical outcome., Results: The use of amlodipine decreased the rates of MI, PTCA, and CABG by 2.0, 4.7, and 2.7%, respectively. The total expected cost per patient using amlodipine was $6,398.30 (US$4,323) in Canada and kr 59,993.27 (US$6,846) in Norway. The total expected cost per patient not using amlodipine was $6,519.37 (US$4,405) in Canada and kr 64,292.17 (US$7,337) in Norway. The model demonstrated potential cost-savings over a 4-month follow up period resulting from the improved clinical outcomes for patients using amlodipine with PTCA--$121,071 (US$81,844) per 1000 patients in Canada and kr 4,298,899 (US$490,074) per 1000 patients in Norway., Conclusions: The adjunctive use of amlodipine is a cost-effective therapeutic strategy to achieve more favorable clinical outcomes in patients undergoing PTCAs in Canada and Norway.

Aim and Methods: The outcome of 1999 apparently healthy men, aged 40-59 years, initially investigated in the period 1972-1975, has previously been ascertained at 7 and 16 year follow-ups. This has now been repeated after 21 years, to determine whether seated systolic blood pressure (BP) during a bicycle ergometer exercise test adds prognostic information on cardiovascular (CV) mortality beyond that of systolic BP measured after 5 min of supine rest., Results: After 21 years, 41 979 years of observation, 470 patients had died, 255 from CV causes. Supine systolic BP [2 SD increase: relative risk (RR) 1.6, 95% confidence interval (CI) 1.3-2.0, P < 0.0001], 6 min exercise systolic BP (2 SD increase: RR 1.6, 95% CI 1.3-2.0, P < 0.0001) on the starting workload of 600 kpm/min (approximately 100 W, 5880 J/min) and maximal systolic BP (2 SD increase: RR 1.5, 95% CI 1.2-1.9, P = 0.0005) during work were all related to CV mortality when adjusting for a large number of variables measured in the present study including age, exercise capacity, heart rates, smoking habits, glucose tolerance and serum cholesterol. When including other systolic BPs in the continuous multivariate analysis, supine systolic BP (2 SD increase: RR 1.4, 95% CI 1.04-1.9, P = 0.029) and 6 min systolic BP at 600 kpm/min (2 SD increase: RR 1.4, 95% CI 1.06-1.9, P = 0.017) were independent predictors of CV death but not maximal systolic BP during exercise (2 SD increase: RR 1.0, 95% CI 0.7-1.2, P = 0.95)., Conclusion: These results are different from the mortality data at 16 years, when the independent predictive effect of supine systolic BP was cancelled out by 6 min exercise systolic BP at 600 kpm/min. Twenty-one years of follow-up of 1999 apparently healthy men disclose independently predictive information on CV death, of both supine systolic BP and 6 min exercise systolic BP taken at an early moderate workload. The influence of maximal exercise systolic BP on CV death is however cancelled out by the two other systolic BPs.

We describe a profoundly retarded infant girl with multiple anomalies caused by trisomy 13. Due to heart failure, which was resistant to medical treatment, we closed successfully a ventricular septal defect at three months of age. She died at 10 months of age. Despite the short survival, we believe that the patient benefitted significantly from the surgical repair of her cardiac defect.

Objective: Although an excess transmission of type 2 diabetes from mothers has been documented, whether this is an independent trait or whether the effect can be detected early through risk factors for type 2 diabetes remains to be elucidated. The objective of this study was to investigate the prevalence of and the possible prospective effect of family history on type 2 diabetes incidence adjusted for multiple diabetes risk factors in a 22.5-year follow-up study of healthy men., Research Design and Methods: A total of 1,947 apparently healthy nondiabetic men with fasting blood glucose (FBG) levels <110 mg/dl at baseline, in whom an intravenous glucose tolerance test (IVGTT) was administered and several conventional risk factors were measured, were followed for 22.5 years. Family history data were obtained at the baseline examination, and morbidity data were obtained from repeated investigations, hospital records, and death certificates., Results: A total of 131 men reported maternal diabetes family history only, 65 men reported paternal diabetes family history only and 10 men reported both maternal and paternal diabetes family history. Among the 1,947 men, 143 cases of type 2 diabetes developed during 22.5 years of observation. Maternal family history and combined maternal and paternal family history predisposed to future type 2 diabetes both in univariate Cox analysis and in multivariate Cox regression analysis after adjusting for glucose disappearance rate (Rd) during an IVGTT, FBG level, BMI, physical fitness, triglyceride level, and age. Maternal family history showed a relative risk (RR) of 2.51 (95% CI 1.55-4.07), combined maternal and paternal family history showed an RR of 3.96 (1.22-12.9), and paternal family history showed an RR of 1.41 (0.657-3.05) in multivariate analysis., Conclusions: Maternal family history appears to be an important risk factor for type 2 diabetes independent of prediabetic Rd, FBG, BMI, and physical fitness levels.

The Coronary AngioPlasty Amlodipine REStenosis Study (CAPARES) is a multicentre, double-blind, placebo controlled restenosis trial investigating the effect of amlodipine on angiographic and clinical endpoints in patients undergoing routine percutaneous transluminal coronary angioplasty (PTCA) for stable angina pectoris. A total of 635 patients were randomized to amlodipine or placebo two weeks before PTCA and were followed for four months after PTCA. There were 451 nonstented patients who completed the study with angiographic follow-up. Quantitative coronary angiography revealed that the loss in minimal luminal diameter from immediately after PTCA to the four-month follow-up was unaffected by amlodipine treatment. However, the incidence of repeat PTCA and composite clinical events were significantly lower in patients treated with amlodipine.

Background: The mechanisms behind development of tolerance to nitrate effects during sustained, asymmetric isosorbide dinitrate (ISDN) therapy are not fully understood., Hypothesis: The study was undertaken to investigate the changes of the relationships between left ventricular (LV) function and plasma concentrations of ISDN and its vasoactive metabolites (2- and 5-ISMO) during acute and sustained, asymmetric ISDN therapy., Methods: Left ventricular function and plasma concentrations of ISDN, 2- and 5-isosorbide mononitrates (P-ISDN, P-2- and 5-ISMO) were measured at rest and at supine exercise before and for 4 h after peroral 30 mg ISDN in 15 patients with coronary artery disease, all with initial exercise pulmonary artery wedge pressure (PAWP) > 25 mmHg. Seven patients were untreated (acute group), while eight received 30 mg ISDN b.i.d. for 2 weeks before the invasive study. P-ISDN and the concentration of available isosorbide-bound nitrate (NO2) in plasma (P-ISDN.2 + P-2-ISMO + P-5-ISMO) (P-NO2) were used as measures of the nitric oxide (NO) offer to the tissues., Results: Throughout the study, after administration of medication, all plasma concentrations, in particular P-ISDN, were higher in the chronic than in the acute group. Peak P-ISDN was reached after 15 min in the chronic group and after 25 min in the acute group, while P-2- and 5-ISMO reached maximum only after 40 min in both groups. At rest, the full effect on PAWP was observed after 10 min in both groups, but at markedly higher levels of P-ISDN and P-NO2 in the chronic group. Afterward, no further changes in PAWP were observed. During exercise, 1 h after medication, PAWP and stroke index to PAWP ratio (SI/PAWP) were normal in both groups. Thereafter, at slowly declining P-NO2, PAWP rose and SI/PAWP declined toward the initial level in the chronic group, but remained unchanged in the acute group, in spite of higher P-NO2 and greater NO release in the former., Conclusions: Patients receiving sustained, asymmetric 30 mg ISDN b.i.d. dosing had the same immediate beneficial effects on LV function during exercise after a morning dose as did untreated patients. However, in spite of higher P-NO2 and higher rate of NO release during sustained treatment, the effects deteriorated gradually 2 to 3 h after medication. The changes in metabolism and/or distribution of isosorbide-bound NO2 may possibly be part of the tolerance induced by long-term treatment, even with asymmetric dosing.

Plasma levels of natriuretic peptides are used as diagnostic markers of heart failure. The aim of this study was to analyse the relation between plasma levels of N-terminal proatrial natriuretic peptide (Nt-proANP) and renal function, and to develop reference values in children. Nt-proANP was measured in the plasma of 86 patients whose glomerular filtration rate (GFR) was determined by use of the X-ray contrast medium iohexol and a fluorescence technique. Blood samples for Nt-proANP were also collected in 399 reference children, aged 0 - 15 years. The relationship between Nt-proANP and GFR was examined using a multiple regression analysis. The mean value of Nt-proANP was markedly higher in children with heart failure than in children with malignant or urologic diseases (p<0.001). The variability in plasma levels of Nt-proANP was mainly (adjusted R2=0.81) explained by the following four variables: presence of heart failure, GFR, age and previous treatment with anthracyclins. Plasma levels of the peptide are raised at birth, but fall rapidly to adult levels. We conclude that the plasma levels of Nt-proANP are age-dependent. Moderately elevated values were registered in children with severe renal impairment. Heart failure is regularly associated with excessive elevation of Nt-proANP in plasma. Our findings suggest that the influence of heart failure on levels of this peptide in children greatly exceeds the influence of renal dysfunction.

Background: Patent ductus arteriosus is increasingly treated with catheter based techniques. We present our results as by the end of 1998 of the first 100 patients given such treatment., Material and Methods: The 100 patients between 0.6 and 31.4 years were initially treated with one of these devices: The Rashkind umbrella (60 patients), Cook PDA coils (31 patients) or Amplatzer ductal occluders (ten patients). Seven umbrella patients were treated twice, one with an additional umbrella, six with coils; two coil patients twice, one with another coil and one--after embolisation--with a peg., Results: The overall complete closure rate for all groups was 90% after nine patients had been treated a second time. The primary complete closure rate in pegs was 100%, after reintervention 85% in umbrella and 97% in coil patients. Neither umbrellas nor pegs have embolised. One coil embolised in the course of implantation of 40 coils (2.5%). No other complication has occurred., Interpretation: The closure of the arterial duct with catheter techniques compares favorably with surgery and is now established as the method of choice. Following the investigational introduction of pegs there is no longer an upper limit in the size of ducts suitable for such treatment.

In order to test the effect of systematic supervised physical training, we divided a total of 129 children and adolescents with congenital heart disease into a group undergoing intervention and a control group. All patients underwent exercise tests, measurements of physical activity, and a survey of psychosocial factors. An improvement in uptake of peak level of oxygen was observed after intervention. There was also an improvement in physical activity in both groups measured by a monitor, although this was significant only in those with intervention. The psychosocial scales measured by the Child Behavior Checklist showed a decrease in internalizing scores for those subjected to intervention. This was decreased due to decreased withdrawal and somatic complaints. In conclusion, we recommend systematic supervised training, including testing of routine follow-ups, in patients with congenital heart disease.

Objectives: Our intent was to investigate the effect of the dihydropyridine calcium channel blocker amlodipine on restenosis and clinical outcome in patients undergoing percutaneous transluminal coronary angioplasty (PTCA)., Background: Amlodipine has sustained vasodilatory effects and relieves coronary spasm, which may reduce luminal loss and clinical complications after PTCA., Methods: In a prospective, double-blind design, 635 patients were randomized to 10 mg of amlodipine or placebo. Pretreatment with the study drug started two weeks before PTCA and continued until four months after PTCA. The primary angiographic end point was loss in minimal lumen diameter (MLD) from post-PTCA to follow-up, as assessed by quantitative coronary angiography (QCA). Clinical end points were death, myocardial infarction, coronary artery bypass graft surgery and repeat PTCA (major adverse clinical events)., Results: Angioplasty was performed in 585 patients (92.1%); 91 patients (15.6%) had coronary stents implanted. Follow-up angiography suitable for QCA analysis was done in 236 patients in the amlodipine group and 215 patients in the placebo group (per-protocol group). The mean loss in MLD was 0.30 +/- 0.45 mm in the amlodipine group versus 0.29 +/- 0.49 mm in the placebo group (p = 0.84). The need for repeat PTCA was significantly lower in the amlodipine versus the placebo group (10 [3.1%] vs. 23 patients [7.3%], p = 0.02, relative risk ratio [RR]: 0.45, 95% confidence interval [CI]: 0.22 to 0.91), and the composite incidence of clinical events (30 [9.4%] vs. 46 patients (14.5%), p = 0.049, RR: 0.65, CI: 0.43 to 0.99) within the four months follow-up period (intention-to-treat analysis)., Conclusions: Amlodipine therapy starting two weeks before PTCA did not reduce luminal loss, but the incidence of repeat PTCA and the composite major adverse clinical events were significantly reduced during the four-month follow-up period after PTCA with amlodipine as compared with placebo.

Background: The effect of percutaneous transluminal coronary angioplasty (PTCA) on physiologic measurements has previously been shown, but the relation between physiologic response and degree of change in coronary luminal diameter is not known. We studied the relation between exercise capacity and minimal luminal diameter before and after PTCA. We also explored the usefulness of measurement of attenuation in exercise capacity after PTCA to predict the likelihood of restenosis., Methods: Bicycle exercise testing was performed 2 weeks before and 2 and 20 weeks after PTCA in 395 consecutively enrolled patients. Angiograms obtained before and after PTCA and 20 weeks afterward were analyzed by quantitative coronary angiography. Restenosis was defined as both angiographic (>/=50% diameter stenosis at follow-up angiography) and clinical (target-vessel revascularization), after successful PTCA. Exercise capacity was defined as the cumulative work performed divided by body weight (watt x minutes x kilograms(-1))., Results: Exercise capacity increased 43% (P <.0001) from before PTCA to 2 weeks after PTCA (early increase) and decreased 4% (P =.01) from 2 to 20 weeks after PTCA (late decrease). The gain in minimal luminal diameter (Minimal luminal diameter after - Minimal luminal diameter before) was 0.92 +/- 0.46 mm. The loss in minimal luminal diameter (Minimal luminal diameter after PTCA - Minimal luminal diameter at follow-up examination) was 0.27 +/- 0.42 mm. Exercise capacity and minimal luminal diameter measured before PTCA were positively correlated (coefficient 3.3; R = 0.12; P =.01). Gain in minimal luminal diameter correlated with the early increase in exercise capacity (coefficient -3.8; R = 0.23; P <.0001). Loss in minimal luminal diameter correlated with the late decrease in exercise capacity (coefficient 3.3; R = 0.20; P <.0001). Multivariate logistic regression analysis revealed that the late decrease in exercise capacity was independently predictive of both angiographically (odds ratio 1.13; P <.0001) and clinically (odds ratio 1.12; P <.0001) defined restenosis., Conclusions: The results demonstrated a linear relation between the severity of coronary stenosis and exercise capacity measured before PTCA. The degree of coronary luminal enlargement achieved with angioplasty and the luminal reduction that occurred between PTCA and follow-up evaluation correlated with increases and decreases in exercise capacity. Attenuation in exercise capacity was found to be a strong predictor of restenosis.

The aim of the present study was to evaluate different aspects of a device designed to monitor physical activity. Measurements of different axes and placement of the monitor were tested using a treadmill with ranging increments in incline or speed. The monitor was also used to assess the level of physical activity among children and adolescents with congenital heart disease and in healthy controls at the same age. The results indicate that the monitor is a valid and reproducible instrument for measurements of physical activity. The study revealed that the level of activity was higher for healthy boys than healthy girls (p<0.0001). Boys with congenital heart disease also displayed higher values compared to girls with congenital heart disease, although the difference was not significant (p=0.067). Healthy boys revealed a significantly higher level of activity than did boys with congenital heart disease (p=0.003), but no such difference was found in girls (p=0.757). Nor were any differences found between younger and older individuals among patients with congenital heart disease. Young healthy controls, however, showed significantly higher levels of activity than their older counterparts. There were differences in activity monitored during the week, with lower activity in the weekends, but the activity on the same day in different weeks seemed stable. Neither were there any differences between measurements over whole weeks. The results indicate that the Computer Science & Application monitor is a valid instrument for assessing physical activity. The monitor may also be used, therefore, to validate the levels of physical activity level in children with congenital heart disease after medical and surgical treatment.

There are about 500 new cases of congenital heart disease per year in Norway. Modern diagnostic skills, surgical techniques and follow-up programs have contributed to higher survival rates among patients. Based on international experience, 85-90 per cent of these children will survive into adulthood. Half will suffer from conditions which should be followed up by cardiologists. This article is based upon recommendations on long-term follow-up of patients with congenital heart disease.

Aims: Lipoproteins and lipids, especially lipoprotein(a), have been studied as risk factors for restenosis after coronary angioplasty with conflicting results. We investigated the association between serum levels of lipoprotein(a) apolipoprotein A-1, apolipoprotein B-100, total-cholesterol, high density lipoprotein-cholesterol, triglycerides, and coronary luminal loss and restenosis after angioplasty., Methods: The lipoproteins and lipids were measured in 305 consecutive patients who underwent successful angioplasty and reangiography 20+/-3 weeks after angioplasty. Single-vessel dilatation was performed in 251 patients. Luminal loss was defined as minimal luminal diameter post-angioplasty minus minimal luminal diameter at follow-up, divided by the interpolated reference diameter of the vessel. Restenosis was defined according to three dichotomous categorical criteria: (1) >50% diameter stenosis at follow-up (2) loss of >50% of the gain achieved by angioplasty, (3) the need for target vessel revascularization., Results: There was no significant association between the serum levels of lipoproteins and lipids and luminal loss. Univariate analysis did not show any significant difference in the serum levels of any of the lipoproteins and lipids between the restenosis and no-restenosis groups. Multivariate analysis revealed that only the angiographic variables (luminal gain and post-angioplasty minimal luminal diameter) were associated with luminal loss and restenosis after angioplasty., Conclusion: Lipoproteins and lipids were neither associated with luminal loss nor independent risk factors for restenosis after angioplasty.

The peak oxygen uptake (VO2(peak)) of 196 healthy children and adolescents aged 8-16 years, and 187 children and adolescents (in the same age range) with congenital heart disease (CHD), was measured using a graded treadmill test (Oslo-protocol). The healthy population was tested to assess the reference values that were to be used in the interpretation of the results obtained from patients with CHD. The results revealed that patients with CHD exhibited lower VO2(peak) values, with declining values for boys after the age of 12-13 years. When separated into different diagnostic groups, on average, patients with a chronic pressure overload of the left ventricle and patients with tetralogy of Fallot have lower VO2(peak) values, but make approximately the same progress with age as healthy subjects. Patients with transposition of the great arteries, however, displayed a marked decline in VO2(peak) after the age of 12-13 years. Whether exercise testing should be included in routine follow-up in patients with CHD, especially those between the ages of 10 and 16 years, when the condition of some patients deteriorates, requires special attention.

Background: The mechanisms underlying exertional hyperpnea in patients with coronary artery disease and transient left ventricular dysfunction are still not fully understood., Hypothesis: The study was undertaken to investigate whether the ventilatory response to exercise reflects the effects of acute medical treatment of exercise-induced left ventricular dysfunction, and to evaluate mechanisms relevant to excessive exertional ventilation., Methods: In 11 male patients, aged 65.2 +/- 6.0 years, all with pulmonary artery wedge pressure (PAWP) > 25 mmHg and ST depression > 2 mm during moderate supine exercise, ventilation (V), oxygen uptake (VO2), hemodynamics, electrocardiogram (ECG), and arterial and mixed venous blood gases were examined during supine rest and exercise, before and at hourly intervals after peroral intake of 30 mg isosorbide dinitrate (ISDN). Six similar patients were examined with the same protocol without ISDN administration and comprised a control group., Results: Before administration of ISDN, exercise PAWP was 35.3 +/- 5.9 mmHg, ECG showed 2.77 +/- 1.06 mm ST depression, and V/VO2 was 31.8 +/- 4.8 l/l. One h after ISDN administration, exercise mean PAWP was 11.0 +/- 2.5 mmHg (p < 0.001), ST depression 0.59 +/- 0.8 mm (p < 0.001), whereas V/VO2 was unchanged, 30.1 +/- 5.3 l/l. Two h later, PAWP remained reduced and there were only minor ST depressions, while V/VO2 remained high. Exercise cardiac index (CI) and mixed venous oxygen tension (PvO2), initially 4.7 +/- 0.67 l/min/m2 and 3.54 +/- 0.35 kPa, respectively, remained at the same low level throughout the study. In the six nontreated patients, there were no significant changes in ST depression, exercise PAWP, or exertional ventilation., Conclusion: Isosorbide dinitrate treatment markedly improved exercise-induced left heart dysfunction, whereas excessive ventilatory response was unaffected, even after 3 h. Thus, measurements of the exercise hyperpnea did not properly reflect effective reduction of myocardial ischemia.

Measurement of plasma levels of natriuretic peptides are now in clinical use in adult patients with heart failure. Experiences in adult medicine cannot be extended to paediatric cardiology due to important physiological differences between adults and children. The haemodynamic background of heart failure in children with congenital heart disease is diverse, and there is no relevant functional or echocardiographic grading system. The authors present results from published studies and summarizes the results of a research project concerning the clinical potential of N-terminal proatrial natriuretic peptide (Nt-proANP) in paediatric cardiology. Peptide levels in newborn children with or without disease are not fully clarified. In children above three months of age, an elevated Nt-proANP value strongly indicates haemodynamic imbalance. This may be important in the follow-up of children with congenital heart disease. A normal value does not exclude the presence of heart disease. A case report illustrates the clinical use of Nt-proANP, and peptide levels in different haemodynamic situations are discussed.

We postulated previously that variables related to pulmonary flow are independent predictors of levels of atrial natriuretic peptide in children with congenital heart disease. The aim of this study was to test this hypothesis in relation to other hemodynamic and clinical variables. During catheterization we measured the levels of plasma N-terminal atrial natriuretic peptide prohormone in the plasma of 68 children with congenital heart disease. All had undergone complete clinical, echocardiographic and invasive hemodynamic investigations. The influence on the prohormone was analyzed for 10 different variables in a multiple linear regression model. The variability could be explained in large parts (adjusted R2 =77.2%) by variations in atrial pressures or sizes, together with the degree of excessive pulmonary blood flow and signs of heart failure. A value for atrial natriuretic peptide prohormone above 800 pmol/l predicted hemodynamic imbalance (defined as elevated pressures in left or right atrium or the pulmonary arteries, and/or Qp/Qs > 1.5) with a specificity of 94%, a sensitivity of 73%, a positive likelihood ratio of 12.2, and a negative likelihood ratio of 0.29. In conclusion, variables related to pulmonary blood flow are influential determinants of the levels of atrial natriureic peptide in children with congenital heart disease. Atrial pressures, and symptoms of heart failure are also of major importance.

The understanding and control of the healing process after percutaneous transluminal coronary angioplasty (PTCA) and of the pathogenesis of restenosis are incomplete. To date, only stent implantation has been shown to successfully reduce the rate of restenosis. Calcium channel blockers have positive effects on a number of processes that may be associated with restenosis, including reduction of platelet aggregation, minimization of vasospasm, and inhibition of mitogens. Clinical trials have therefore been performed to assess the effect of calcium channel blockers on restenosis and ischemia. A meta-analysis of five restenosis trials investigating calcium channel blockers demonstrated a 30% reduction in the risk for restenosis. The Coronary Angioplasty Amlodipine Restenosis Study (CAPARES) is therefore assessing the effect of amlodipine, a long-acting, third-generation calcium channel blocker in angioplasty patients. Therapy (amlodipine 5 mg with a forced titration to 10 mg once daily, or placebo), is begun 2 weeks before angioplasty and is continued for 4 months after the procedure. The rationale of CAPARES is that amlodipine may offer anti-ischemic protection before, during, and after angioplasty, may have more beneficial effects on restenosis and various clinical end points than calcium channel blockers used in previous trials, and may improve the long-term outcome of PTCA therapy.