B.J.M. Mulder

Brain Natriuretic Peptide as a Predictor of Adverse Outcome in Patients With Pulmonary Embolism

Background—Despite effective treatment with anticoagulants, 2% to 7% of patients with pulmonary embolism will die as a result of their disease. Methods and Results—We examined in 110 consecutive patients with pulmonary embolism whether plasma brain natriuretic peptide (BNP), a novel marker of (right) ventricular dysfunction, is a predictor of fatal pulmonary embolism. The relationship between BNP concentration measured at presentation and clinical outcome was assessed by comparing the proportion of outcome events among tertiles. Positive and negative predictive values of BNP levels in the highest and lowest tertiles were calculated. The risk of death related to pulmonary embolism if the BNP level is >21.7 pmol/L is 17% (95% CI, 6% to 33%). The negative predictive value for uneventful outcome of a BNP value <21.7 pmol/L is 99% (95% CI, 93% to 100%). Conclusion—This is the first study to show that plasma BNP levels seem to predict adverse outcome in patients with acute pulmonary embolism.

Increased brain and atrial natriuretic peptides in patients with chronic right ventricular pressure overload: correlation between plasma neurohormones and right ventricular dysfunction

OBJECTIVE To evaluate the role of plasma neurohormones in the diagnosis of asymptomatic or minimally symptomatic right ventricular dysfunction. SETTING Tertiary cardiovascular referral centre. METHODS Plasma brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) concentrations were measured in 21 asymptomatic or minimally symptomatic patients with chronic right ventricular pressure overload caused by congenital heart disease, and in seven healthy volunteers. Right ventricular ejection fraction was determined using magnetic resonance imaging. RESULTS Right ventricular ejection fraction in the volunteers was higher than in the patients (69.0 (8.2)% v 58.0(12.0)%, respectively; pu2009<u20090.006). Left ventricular ejection fraction was 72.3(7.8)% in volunteers and 68.1(11.0)% in patients (NS). There was a significant difference between patients and volunteers in the plasma concentrations of BNP (5.3 (3.5) v 2.3 (1.7)u2009pmol/l, respectively; pu2009<u20090.009) and ANP (7.3 (4.5)v 3.6 (1.4)u2009pmol/l; pu2009<u20090.05). In both patients and volunteers, mean plasma ANP was higher than mean plasma BNP. Right ventricular ejection fraction was inversely correlated with BNP and ANP (respectively, ru2009=u20090.65; pu2009<u20090.0002 and ru2009=u20090.61; pu2009<u20090.002). There was no correlation between left ventricular ejection fraction and BNP (ru2009=u20090.2; NS) or ANP (ru2009=u20090.52; NS). Similarly, no correlation was shown between the level of right ventricular systolic pressure and either plasma BNP (ru2009=u20090.20) or plasma ANP (ru2009=u20090.07). CONCLUSIONS There was a significant inverse correlation between right ventricular ejection fraction and the plasma neurohormones BNP and ANP in asymptomatic or minimally symptomatic patients with right ventricular pressure overload and congenital heart disease. Monitoring changes in BNP and ANP may provide quantitative follow up of right ventricular dysfunction in these patients.

Survival and complication free survival in Marfan’s syndrome: implications of current guidelines

OBJECTIVE To evaluate survival and complication free survival in patients with Marfan’s syndrome and to assess the possible influence of recently revised guidelines for prophylactic aortic root replacement in these patients. METHODS 130 patients who had been attending one institution over 14 years were evaluated. Kaplan–Meier analysis was performed in 125 patients who did not present with aortic root dissection as the first sign of Marfan’s syndrome, with the end points: death, aortic root dissection, and prophylactic aortic root replacement after diagnosis. In the patients developing aortic root dissection, current guidelines for prophylactic aortic root replacement were retrospectively applied to investigate the number of dissections that could theoretically have been prevented. The guidelines were: (1) aortic root diameter ⩾u200955 mm, (2) positive family history of aortic dissections and aortic root diameter ⩾u200950 mm, and (3) aortic root growth ⩾u20092 mm/year. Outcomes following emergency surgery (15 patients) and prophylactic surgery of the aortic root (30 patients) were compared. RESULTS Five and 10 year survival after diagnosis was 95% and 88%, and the five and 10 year complication free survival was 78% and 66%, respectively. Thirteen patients developed dissection, 30 underwent prophylactic repair, and 82 had an uncomplicated course. Eleven dissections could theoretically have been prevented by application of the current guidelines. Five year survival following emergency and prophylactic repair of the aortic root was 51%, and 97%, respectively. CONCLUSIONS Survival in the Marfan’s syndrome in the past 14 years seems satisfactory; with application of current guidelines, it has probably even improved. However, because of the high fatality rate in Marfan patients developing aortic root dissection, more extensive screening for Marfan’s syndrome and a search for additional risk factors are desirable.

Pregnancy and delivery in women after Fontan palliation.

Objectives: To evaluate the outcome of pregnancy in women after Fontan palliation and to assess the occurrence of infertility and menstrual cycle disorders. Design and patients: Two congenital heart disease registries were used to investigate 38 female patients who had undergone Fontan palliation (aged 18–45 years): atriopulmonary anastomosis (n u200a=u200a 23), atrioventricular connection (n u200a=u200a 5) and total cavopulmonary connection (n u200a=u200a 10). Results: Six women had 10 pregnancies, including five miscarriages (50%) and one aborted ectopic pregnancy. During the remaining four live-birth pregnancies clinically significant complications were encountered: New York Heart Association class deterioration; atrial fibrillation; gestational hypertension; premature rupture of membranes; premature delivery; fetal growth retardation and neonatal death. Four of seven women who had attempted to become pregnant reported female infertility: non-specified secondary infertility (n u200a=u200a 2), uterus bicornis (n u200a=u200a 1) and related to endometriosis (n u200a=u200a 1). Moreover, several important menstrual cycle disorders were documented. In particular, the incidence of primary amenorrhoea was high (n u200a=u200a 15, 40%), which resulted in a significant increase in age at menarche (14.6 (SD 2.1) years, p < 0.0001, compared with the general population). Conclusion: Women can successfully complete pregnancy after adequate Fontan palliation without important long-term sequelae, although it is often complicated by clinically significant (non-)cardiac events. In addition, subfertility or infertility and menstrual disorders were common.

Pregnancy, fertility, and recurrence risk in corrected tetralogy of Fallot.

Objective: To determine in women with surgically corrected tetralogy of Fallot the risk of pregnancy for mother and fetus, whether fertility was compromised, and the recurrence risk of congenital heart disease. Design: Data were collected from 83 patients through interviews and review of medical records. Results: In 29 patients 63 pregnancies were observed, of which 13 ended in an abortion. Fifty successful pregnancies were observed in 26 patients. During six successful pregnancies (12%) complications (symptomatic right sided heart failure, arrhythmias, or both) occurred. Both patients who developed symptomatic heart failure had severe pulmonary regurgitation. No clear relation between offspring mortality, premature birth or being small for gestational age, and cardiac characteristics of the mother was identified. Fifty seven patients were childless (41 (72%) voluntarily). Recurrence risk for congenital heart disease was 2.2%. Infertility was uncommon. Conclusions: Although complications did occur in five of 26 (19%) of the patients with a corrected tetralogy of Fallot, pregnancy was generally well tolerated in this largest report so far. No obvious predictors for maternal events or child outcome were determined, except for a possible relation between severe pulmonary regurgitation and symptomatic heart failure.

Non-cardiac complications during pregnancy in women with isolated congenital pulmonary valvar stenosis

Background: Information on the outcome of pregnancy in patients with pulmonary valvar stenosis is scarce, mostly limited to cardiac complications observed during pregnancy. Objectives: To investigate the magnitude and determinants of non-cardiac and fetal risks during pregnancy of women with isolated pulmonary valvar stenosis. Methods: Using the nationwide registry (CONgenital CORvitia), 106 women with (un-)corrected pulmonary valvar stenosis receiving care in six tertiary medical centres in The Netherlands were included. A total of 51 women had 108 pregnancies, including 21 (19%) miscarriages and 6 elective abortions. Results: In the 81 completed (>20 weeks of gestation) pregnancies, we observed a high number of hypertension-related disorders (nu200a=u200a12, 15%, including pre-eclampsia (nu200a=u200a4) and eclampsia (nu200a=u200a2)), premature deliveries (nu200a=u200a14, 17%, including one twin) and thromboembolic events (nu200a=u200a3, 3.7%). Furthermore, recurrence of congenital heart defects in the offspring was detected in three children (3.7%, pulmonary valvar stenosis (nu200a=u200a2) and complete transposition of the great arteries in combination with anencephaly). In addition to the intrauterine fetal demise of the transposition child, three other children died shortly after birth owing to immaturity, hydrocephalus combined with prematurity and meningitis (overall offspring mortality, 4.8%). Conclusion: In this largest report on pregnancy in women with (un-) corrected isolated pulmonary valvar stenosis, an excessive number of (serious) non-cardiac complications and mortality were observed in the offspring.

Marfan syndrome in children and adolescents: an adjusted nomogram for screening aortic root dilatation

Objective To construct an adjusted nomogram for the echocardiographic screening of aortic root diameter in children with possible Marfan disease. Design In 91 children (42 boys, 49 girls, age range 3.2 to 18.4 years) undergoing Marfan screening from 1983 until 1996, the diagnosis Marfan syndrome and any other aortic pathology was definitely ruled out. These served as a control population to set appropriate reference standards. Results Compared with a standard Dutch reference population, body surface area of the control subjects (mean (SD)) was above the 50th centile (boys 0.09u2009(0.20)u2009m2, range −0.28 to 0.69u2009m2; girls 0.09u2009(0.17)u2009m2, range −0.17 to 0.69u2009m2). Echocardiographically determined aortic root diameter and body surface area showed a linear relation and a greater variability of aortic root diameter in these relatively tall subjects (nu2009=u200991,R 2u2009=u20090.62) than in the standard nomogram (nu2009=u200956, R 2u2009=u20090.93). In 24% of cases (nu2009=u200922), the aortic root exceeded the upper limit of normal in the standard nomogram, by 2.2u2009(2.0)u2009mm. An adjusted nomogram was constructed with a higher upper limit. Conclusions A Marfan screening population differs from the unselected population in body surface area and aortic root size variability. An adjusted nomogram should therefore be used to detect a truly enlarged aortic root.

Marfan syndrome in children and adolescents: predictive and prognostic value of aortic root growth for screening for aortic complications

Objective To assess and measure the diagnostic and prognostic value of individual aortic root growth in children and adolescents with Marfan syndrome. Design From 1983 to 1996, 250 children were screened for Marfan syndrome. Serial echocardiographic aortic root measurements of 123 children (57 Marfan, 66 control) were available for evaluation of aortic root growth. Aortic root diameters were correlated with body surface area. Based on individual growth of the aortic root a discrimination formula was derived to distinguish Marfan patients from control subjects. Results Sensitivity and specificity of this method, which were dependent on the number of measurements, were 84% and 73%, respectively, for three serial measurements. The discrimination score also predicted a five year complication free survival in all patients. Conclusions In children and adolescents with Marfan syndrome, aortic root growth differs significantly from subjects in whom Marfan syndrome was definitely ruled out during screening. Measurement of individual aortic root growth may serve to establish diagnosis at an early stage and is of prognostic value for occurrence of aortic complications.

ECG determinants in adult patients with chronic right ventricular pressure overload caused by congenital heart disease: relation with plasma neurohormones and MRI parameters

Objective: To examine retrospectively the changes in ECG parameters over time and their correlation with other quantitative right ventricular (RV) function parameters in patients with chronic RV pressure overload caused by congenital heart disease. Methods: 48 patients with chronic RV pressure overload caused by the following congenital heart diseases were studied: nine with congenitally corrected transposition of the great arteries (TGA), 12 with surgically corrected TGA, and 27 with a subpulmonary pressure overloaded RV. QRS duration and dispersion were measured manually from standard ECG recorded twice within five years. RV end diastolic volume (EDV) and RV mass were determined by magnetic resonance imaging. Brain natriuretic peptide (BNP) plasma concentrations were measured. Results: QRS duration and QRS dispersion increased in all patient groups during the follow up period. QRS duration increased significantly in the congenitally corrected TGA (p = 0.04) and the subpulmonary pressure overloaded RV groups (p = 0.01). QRS dispersion increased significantly in patients with surgically corrected TGA (p = 0.03) and in the subpulmonary pressure overloaded RV group (p = 0.02). A significant correlation was found between QRS duration and RVEDV (r = 0.71, p < 0.0001). RV mass was significantly correlated with QRS duration in patients with tetralogy of Fallot (r = 0.67, p = 0.01). Mean (SD) plasma brain natriuretic peptide concentrations (6.6 (5.4) pmol/l) were increased compared with normal reference values but no correlation was found with ECG parameters or RV systolic pressure. No malignant arrhythmia or sudden death occurred. Conclusions: ECG parameters worsened gradually in asymptomatic or minimally symptomatic patients with chronic RV pressure overload, regardless of the nature of their congenital heart disease. In all patients, a significant positive correlation was found between QRS duration and RVEDV. In patients with tetralogy of Fallot there was also a correlation between QRS duration and RV mass.

A comparison of internal mammary artery and saphenous vein grafts after coronary artery bypass surgery. No difference in 1-year occlusion rates and clinical outcome. CABADAS Research Group of the Interuniversity Cardiology Institute of The Netherlands.

BACKGROUNDnSuperior patency rates for internal mammary artery (IMA) grafts compared with vein coronary bypass grafts have been demonstrated by retrospective studies. This difference may have been affected by selection bias of patients and coronary arteries for IMA grafting.nnnMETHODS AND RESULTSnTo estimate the difference between IMA and vein grafts, we analyzed graft patency data of 912 patients who entered a randomized clinical drug trial. In this trial, 494 patients received both IMA and vein grafts (group 1) and 418 only vein grafts (group 2). Occlusion rates of IMA grafts and IMA plus vein grafts in group 1 were compared with those of vein grafts in group 2. Multivariate analysis was used to compare occlusion rates of IMA and vein grafts while other variables related to graft patency were controlled for. In addition, 1-year clinical outcome was assessed by the incidence of myocardial infarction, thrombosis, major bleeding, and death. Occlusion rates of distal anastomoses in group 1 versus group 2 were 5.4% (IMA grafts) versus 12.7% (vein grafts) (P < .0001) and 10.4% (IMA plus vein grafts) versus 12.7% (vein grafts) (P = .14). There was no difference in adjusted risk of occlusion between IMA grafts and vein grafts (P = .089). Type and location of distal anastomosis and lumen diameter of the grafted coronary artery were shown to be predictors of occlusion. Clinical events occurred in 17.8% (group 1) and 16.0% (group 2) of patients (P = .53).nnnCONCLUSIONSnThe observed difference in 1-year occlusion rates between IMA and vein grafts can be explained by a maldistribution of graft characteristics by selection of coronary arteries for IMA grafting rather than being ascribed to graft material. One-year clinical outcome is not improved by IMA grafting.