Intramolecular locking and coumarin insertion: a stepwise approach for TADF design.

Three novel TADF (thermally activated delayed fluorescence) emitters based on the well-studied Qx-Ph-DMAC fluorophore are designed and synthesized. The photophysical properties of these materials are studied from a theoretical and experimental point of view, demonstrating the cumulative effects of multiple small modifications that combine to afford significantly improved TADF performance. First, an extra phenyl ring is added to the acceptor part of Qx-Ph-DMAC to increase the conjugation length, resulting in BQx-Ph-DMAC, which acts as an intermediate molecular structure. Next, an electron-deficient coumarin unit is incorporated to fortify the electron accepting ability, affording ChromPy-Ph-DMAC with red-shifted emission. Finally, the conjugated system is further enlarged by 'locking' the molecular structure, generating DBChromQx-DMAC with further red-shifted emission. The addition of the coumarin unit significantly impacts the charge-transfer excited state energy levels with little effect on the locally excited states, resulting in a decrease of the singlet-triplet energy gap. As a result, the two coumarin-based emitters show considerably improved TADF performance in 1 w/w% zeonex films when compared to the initial Qx-Ph-DMAC structure. 'Locking' the molecular structure further lowers the singlet-triplet energy gap, resulting in more efficient reverse intersystem crossing and increasing the contribution of TADF to the total emission.

Prognostic value of the coronary artery calcium score in suspected coronary artery disease: a study of 644 symptomatic patients.

AIM: The long-term value of coronary artery calcium (CAC) scanning has not been studied extensively in symptomatic patients, but was evaluated by us in 644 consecutive patients referred for stable chest pain. METHODS: We excluded patients with a history of cardiovascular disease and with a CAC score of zero. CAC scanning was done with a 16-row MDCT scanner. Endpoints were: (a) overall mortality, (b) mortality or non-fatal myocardial infarction and (c) the composite of mortality, myocardial infarction or coronary revascularisation. Revascularisations within 1 year following CAC scanning were not considered. RESULTS: The mean age of the 320 women and 324 men was 63 years. Follow-up was over 8 years. There were 58 mortalities, while 22 patients suffered non-fatal myocardial infarction and 24 underwent coronary revascularisation, providing 104 combined endpoints. Cumulative 8­year survival was 95% with CAC score <100, 90% in patients with CAC score >100 and <400, and 82% with CAC score ≥400 Agatston units. Risk of mortality with a CAC score >100 and ≥400 units was 2.6 [95% confidence interval (CI) 1.23-5.54], and 4.6 (95% CI 2.1-9.47) respectively. After correction for clinical risk factors, CAC score remained independently associated with increased risk of cardiac events. CONCLUSIONS: Risk increased with increasing CAC score. Patients with CAC >100 or ≥400 Agatston units were at increased risk of major adverse cardiac events and are eligible for preventive measures. CAC scanning provided incremental prognostic information to guide the choice of diagnostic and therapeutic options in many subjects evaluated for chest pain.

Implementation of the 2015 European Society of Cardiology guidelines for the management of infective endocarditis in the Netherlands.

Because the occurrence of infective endocarditis (IE) continues to be associated with high mortality, a working group was created by the Dutch Society of Cardiology to examine how the most recent European Society of Cardiology (ESC) guidelines for IE management could be implemented most effectively in the Netherlands. In order to investigate current Dutch IE practices, the working group conducted a country-wide survey. Based on the results obtained, it was concluded that most ESC recommendations could be endorsed, albeit with some adjustments. For instance, the suggested pre-operative screening and treatment of nasal carriers of Staphylococcus aureus as formulated in the ESC guideline was found to be dissimilar to current Dutch practice, and was therefore made less restrictive. The recently adapted ESC diagnostic criteria for IE were endorsed, while the practical employment of the relevant diagnostic techniques was simplified in an adapted flowchart. In addition, the presence of a multidisciplinary, so-called 'endocarditis team' in tertiary centres was proposed as a quality indicator. An adapted flowchart specifically tailored to Dutch practice for microbiological diagnostic purposes was constructed. Lastly, the working group recommended the Stichting Werkgroep Antibioticabeleid (SWAB; Dutch Working Party on Antibiotic Policy) guidelines for IE treatment instead of the antibiotic regimens proposed by the ESC.

Diagnostic re-classification and prognostic risk stratification of patients with acute chest pain.

Unstable angina and myocardial infarction are prevalent manifestations of acute coronary artery disease, combined in the term 'acute coronary syndromes'. The introduction of sensitive markers for myocardial necrosis has led to confusion regarding the distinction between small myocardial infarctions and 'true' unstable angina, and the application of ever more sensitive markers has accelerated the pace at which patients with unstable angina are being re-classified to non-ST-segment elevation myocardial infarction. But in how many patients with acute chest pain is myocardial ischaemia really the cause of their symptoms? Numerous studies have shown that most have <5 ng/l high-sensitivity cardiac troponin, and that their prognosis is excellent (event rate <0.5% per year), incompatible with 'impending infarction'. This marginalisation of patients with unstable angina pectoris should lead to the demise of this diagnosis. Without unstable angina, the usefulness of the term acute coronary syndromes may be questioned next. It is better to abandon the term altogether and revert to the original diagnosis of thrombus-related acute coronary artery disease, myocardial infarction. A national register should be the next logical step to monitor and guide the application of effective therapeutic measures and clinical outcomes in patients with myocardial infarction.

Heart disease in the Netherlands: a quantitative update.

In this review we discuss cardiovascular mortality, incidence and prevalence of heart disease, and cardiac interventions and surgery in the Netherlands. We combined most recently available data from various Dutch cardiovascular registries, Dutch Hospital Data (LMR), Statistics Netherlands (CBS), and population-based cohort studies, to provide a broad quantitative update. The absolute number of people dying from cardiovascular diseases is declining and cardiovascular conditions are no longer the leading cause of death in the Netherlands. However, a substantial burden of morbidity persists with 400,000 hospitalisations for cardiovascular disease involving over 80,000 cardiac interventions annually. In the Netherlands alone, an estimated 730,000 persons are currently diagnosed with coronary heart disease, 120,000 with heart failure, and 260,000 with atrial fibrillation. These numbers emphasise the continuous need for dedicated research on prevention, diagnosis, and treatment of heart disease in our country.

Levels and trends in cardiovascular risk factors and drug treatment in 4837 elderly Dutch myocardial infarction patients between 2002 and 2006.

BACKGROUND: It is important to gain insight into opportunities for secondary prevention of cardiovascular disease. Our aim was to investigate levels and trends in cardiovascular risk factors and drug treatment in Dutch post-myocardial infarction (MI) patients between 2002 and 2006 and to make comparisons with the EUROASPIRE surveys (1999-2007). METHODS: We analysed data from 4837 post-MI patients (aged 69 years, 78% men) from 32 Dutch hospitals, using baseline cross-sectional data from the Alpha Omega Trial. RESULTS: Between 2002 and 2006, significant declines were found in the prevalence of smoking (23% to 16%, p < 0.001), hypercholesterolaemia (≥5 mmol/l; 54% to 27%, p < 0.0001) and hypertension (≥140/90 mmHg; 58% to 48%, p < 0.001). The prevalence of antithrombotic drugs was high (97%). The prevalence of lipid-modifying drugs and antihypertensives was high, and increased (74% to 90%, p < 0.0001 and 82% to 93%, p < 0.001, respectively). The prevalence of obesity (27%) was high in 2002 and decreased to 24% in 2006, albeit not significantly. Diabetes prevalence was high and increased between 2002 and 2006 (18% to 22%, p = 0.02). In comparison with EUROASPIRE patients, who were on average 8-10 years younger, our study in 2006 included patients with lower levels of obesity, hypertension, hypercholesterolaemia, diabetes and lower use of antiplatelets and ß-blockers, but similar levels of lipid-modifying drugs. CONCLUSIONS: This study showed that older Dutch post-MI patients were adequately treated with drugs, and that risk factors reached lower levels than in the younger EUROASPIRE patients. However, there is room for improvement in diet and lifestyle, given the high prevalence of smoking, obesity, and diabetes.

Injectable alginate hydrogels for synergistic tumor combination therapy through repolarization of tumor-associated macrophages.

Locally administered drug delivery systems are promising as they allow to circumvent the side effects associated with systematic administration. In this study, we constructed multifunctional hydrogels by simply mixing commercial alginate (ALG) sols with glucose oxidase (GOx)-conjugated polyacrylic acid-stabilized iron oxide nanoparticles (GPI NPs) and Toll-like receptor 7/8 agonist resiquimod (R848). The injectable sols were able to transform into hydrogels (GPI/R848@ALG) by the ionic cross-linking between ALG and physiological Ca2+ to trap the therapeutic components within the hydrogel framework. Upon intratumoral injection, the hydrogels were employed for starvation therapy, promoted chemodynamic therapy and tumor-associated macrophages (TAMs) repolarization. The energy supply was blocked by consuming the intratumoral glucose via the GOx-catalyzed conversion of glucose into gluconic acid and hydrogen peroxide (H2O2).In vitro results showed that the generated H2O2 could be further converted into highly cytotoxic hydroxyl radicals (·HO) by the Fenton reaction to induce enhanced chemodynamic therapy. The TAMs repolarization studies in vitro exhibited that the GPI/R848@ALG hydrogels up-regulated the expression of CD86 by 63% and down-regulated the proportion of CD206 by 14% with a synergistic effect of the presence of Fe3O4 and R848, suggesting that the multifunctional hydrogels exert functions to direct the remodeling of TAMs from the tumor supportive M2-like phenotype to the tumor destructive M1-like phenotype to further contribute to the antitumor effect. Moreover, both in vitro and in vivo experiments demonstrate that the multifunctional hydrogels exhibit admirable antitumor performance towards 4T1 tumors. This work thereby provides a promising multifunctional nanoplatform for synergistic cancer starvation therapy, chemodynamic therapy and TAMs repolarization.

A novel experimental setup for evaluating the stiffness of ankle foot orthoses.

OBJECTIVE: The purpose of this study was the construction of a new semi-automated experimental setup for the evaluation of the stiffness of ankle foot orthoses (AFOs) around an axis aligned to the anatomical ankle joint during the second rocker of the gait. The setup, developed in close collaboration with the orthopedic device company V!GO NV (Wetteren, Belgium), allows measurement of plantarflexion and dorsiflexion in the sagittal plane for a maximal range of motion of 50° (- 25° plantarflexion up to 25° dorsiflexion) in a non-destructive way. RESULTS: The mechanical properties of four 3D printed AFOs are investigated, based on the ranges of motion derived from the gait assessment of the patients when they walked with their AFO. The reliability of the stiffness measures was studied by the evaluation of the test-retest repeatability and the intra-tester and inter-tester variability. These studies revealed that the ankle stiffness can be measured with high reliability (ICC = 0.94-1.00). The obtained outcomes indicate that the experimental setup could be applied to measure the ankle stiffness of any topology of AFOs and, in the future, help finding the correlation with the information coming from the gait assessment of the patients.

Smoking cessation in European patients with coronary heart disease. Results from the EUROASPIRE IV survey: A registry from the European Society of Cardiology.

OBJECTIVE: We investigated smoking cessation rates in coronary heart disease (CHD) patients throughout Europe; current and as compared to earlier EUROASPIRE surveys, and we studied characteristics of successful quitters. METHODS: Analyses were done on 7998 patients from the EUROASPIRE-IV survey admitted for myocardial infarction, unstable angina and coronary revascularisation. Self-reported smoking status was validated by measuring carbon monoxide in exhaled air. RESULTS: Thirty-one percent of the patients reported being a smoker in the month preceding hospital admission for the recruiting event, varying from 15% in centres from Finland to 57% from centres in Cyprus. Smoking rates at the interview were also highly variable, ranging from 7% to 28%. The proportion of successful quitters was relatively low in centres with a low number of pre- event smokers. Overall, successful smoking cessation was associated with increasing age (OR 1.50; 95% CI 1.09-2.06) and higher levels of education (OR 1.38; 95% CI 1.08-1.75). Successful quitters more frequently reported that they had been advised (56% vs. 47%, p < .001) and to attend (81% vs. 75%, p < .01) a cardiac rehabilitation programme. CONCLUSION: Our study shows wide variation in cessation rates in a large contemporary European survey of CHD patients. Therefore, smoking cessation rates in patients with a CHD event should be interpreted in the light of pre-event smoking prevalence, and caution is needed when comparing cessation rates across Europe. Furthermore, we found that successful quitters reported more actions to make healthy lifestyle changes, including participating in a cardiac rehabilitation programme, as compared with persistent smokers.

Retention and release of Zn and Cd in spodic horizons as determined by pH(stat) analysis and single extractions.

In the northern Campine in Belgium, large areas are contaminated by heavy metals such as Zn and Cd due to the (former) non-ferro metal industry. In the sandy soils, the heavy metal adsorption/attenuation in the spodic horizon represents the main retention mechanism of leached pollutants from the contaminated topsoils. In this study, the pH-dependent behaviour of the elements in these spodic horizons was tested by pH(stat) experiments and compared to sandy loam soils. Extractions with CaCl(2) 0.01 M and EDTA 0.05 M provided a further insight into the binding mechanisms. The results indicate that organic matter is the main factor responsible for the mobility of Cd, Zn and Ca in the spodic horizons. The binding of elements is not very strong, however, and highly dependent on pH. A slight decrease in pH can cause a significant release of metals from the spodic horizons, with up to 60% of Cd and 90% of Zn being released within a 1.5 unit change in pH (starting from the naturally occurring pH). This pH change can happen rapidly in these soils, due to the low buffering capacity, and is realistic given the acidification in Flanders. For the sandy loam soils, a pH decrease of 3 units is needed to release 40% of Cd and 20% of Zn, and the acid neutralization capacity is exhausted more gradually, suggesting that slower buffering mechanisms take place. For the sandy loam soils, Cd retention is mainly governed by organic matter, while for Zn other factors such as the clay minerals also play an important role. Despite the high potential mobility and pH dependence of the heavy metal retention in the spodic horizons, the actual risk for groundwater pollution is limited. For the diffusely contaminated areas, where traditional remediation is not an option, spodic horizons may therefore contribute to a natural attenuation of the soil contamination.

[Secondary prevention of coronary heart disease: results of Euroaspire IV]. / Secundaire preventie van coronaire hartziekte.

OBJECTIVE: Secondary prevention is an important part of cardiovascular risk management. Since 1996, an inventory of cardiovascular risk factors and their treatment has been carried out periodically among patients with coronary heart disease within the framework of the European Action on Secondary Prevention by Intervention to Reduce Events (Euroaspire) project. DESIGN: Retrospective investigation of consecutively hospitalised patients with coronary heart disease. METHOD: Major cardiovascular risk factors and their treatment were investigated using standardised methods in patients who were hospitalised following a first heart infarction or with coronary revascularisation in the Amsterdam and Rijnmond regions of the Netherlands from 2012 to 2013. The investigations were carried out at an average of 18 months after admission. In addition, an oral glucose-tolerance test was carried out in patients without known diabetes. RESULTS: We studied 498 patients. The average BMI was 28 kg/m2, almost 75% had a BMI ≥ 25 kg/m2and 29% had a BMI ≥ 30 kg/m2. The mean cholesterol level was 4.4 mmol/l. Among those included, 16% smoked and 20% had diabetes mellitus; the oral glucose-tolerance test led to a new diabetes-mellitus diagnosis in 1% of the patients without known diabetes. A large majority of those included used antihypertensive agents, and slightly more than half used two or more medications. Despite this, half of the patients were hypertensive. CONCLUSION: As far as cardiovascular risk factors are concerned, smoking has almost halved in the past 20 years. Secondary preventative medication has increased to a stable high level. Blood pressure and overweight continue to be serious points for attention. Treatment of hypertension, in particular, should be improved, for instance by dose increases or combination of hypertensive medications. Routine oral glucose-tolerance tests are not useful in cardiac patients.

Predictors of outcome in patients with acute coronary syndromes without persistent ST-segment elevation. Results from an international trial of 9461 patients. The PURSUIT Investigators.

BACKGROUND: Appropriate treatment policies should include an accurate estimate of a patient's baseline risk. Risk modeling to date has been underutilized in patients with acute coronary syndromes without persistent ST-segment elevation. METHODS AND RESULTS: We analyzed the relation between baseline characteristics and the 30-day incidence of death and the composite of death or myocardial (re)infarction in 9461 patients with acute coronary syndromes without persistent ST-segment elevation enrolled in the PURSUIT trial [Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin (eptifibatide) Therapy]. Variables examined included demographics, history, hemodynamic condition, and symptom duration. Risk models were created with multivariable logistic regression and validated by bootstrapping techniques. There was a 3.6% mortality rate and 11.4% infarction rate by 30 days. More than 20 significant predictors for mortality and for the composite end point were identified. The most important baseline determinants of death were age (adjusted chi(2)=95), heart rate (chi(2)=32), systolic blood pressure (chi(2)=20), ST-segment depression (chi(2)=20), signs of heart failure (chi(2)=18), and cardiac enzymes (chi(2)=15). Determinants of mortality were generally also predictive of death or myocardial (re)infarction. Differences were observed, however, in the relative prognostic importance of predictive variables for mortality alone or the composite end point; for example, sex was a more important determinant of the composite end point (chi(2)=21) than of death alone (chi(2)=10). The accuracy of the prediction of the composite end point was less than that of mortality (C-index 0.67 versus 0.81). CONCLUSIONS: The occurrence of adverse events after presentation with acute coronary syndromes is affected by multiple factors. These factors should be considered in the clinical decision-making process.

Clinical significance of thrombocytopenia during a non-ST-elevation acute coronary syndrome. The platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrilin therapy (PURSUIT) trial experience.

BACKGROUND: The significance of thrombocytopenia in patients experiencing an acute coronary syndrome (ACS) has not been examined systematically. We evaluated this condition in a large non-ST-elevation ACS clinical trial, with particular interest paid to its correlation with clinical outcomes. METHODS AND RESULTS: Patients presenting without persistent ST elevation during an ACS were randomized to receive a double-blind infusion of the platelet glycoprotein (GP) IIb/IIIa inhibitor eptifibatide or placebo in addition to other standard therapies including heparin and aspirin. The primary end point was death/nonfatal myocardial infarction (MI) at 30 days, whereas bleeding and stroke were the main safety outcomes. Thrombocytopenia (nadir platelet count <100x10(9)/L or <50% of baseline) occurred in 7.0% of enrolled patients. The time to onset was a median of 4 days in both treatment arms. Patients with thrombocytopenia were older, weighed less, were more likely nonwhite, and had more cardiac risk factors. These patients experienced significantly more bleeding events: they were more than twice as likely to experience moderate/severe bleeding after adjustment for confounders. Univariably, ischemic events (stroke, MI, and death) occurred significantly (P<0.001) more frequently in patients with thrombocytopenia; multivariable regression modeling preserved this association with death/nonfatal MI at 30 days. Neither the use of heparin or eptifibatide was found to independently increase thrombocytopenic risk. CONCLUSIONS: Although causality between thrombocytopenia and adverse clinical events could not be established definitively, thrombocytopenia was highly correlated with both bleeding and ischemic events, and the presence of this condition identified a more-at-risk patient population.

Stroke in patients with acute coronary syndromes: incidence and outcomes in the platelet glycoprotein IIb/IIIa in unstable angina. Receptor suppression using integrilin therapy (PURSUIT) trial. The PURSUIT Investigators.

BACKGROUND: The incidence of stroke in patients with acute coronary syndromes has not been clearly defined because few trials in this patient population have been large enough to provide stable estimates of stroke rates. METHODS AND RESULTS: We studied the 10 948 patients with acute coronary syndromes without persistent ST-segment elevation who were randomly assigned to placebo or the platelet glycoprotein IIb/IIIa receptor inhibitor eptifibatide in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial to determine stroke rates, stroke types, clinical outcomes in patients with stroke, and independent baseline clinical predictors for nonhemorrhagic stroke. Stroke occurred in 79 (0.7%) patients, with 66 (0.6%) nonhemorrhagic, 6 intracranial hemorrhages, 3 cerebral infarctions with hemorrhagic conversion, and 4 of uncertain cause. There were no differences in stroke rates between patients who received placebo and those assigned high-dose eptifibatide (odds ratios and 95% confidence intervals 0.82 [0.59, 1.14] and 0.70 [0.49, 0.99], respectively). Of the 79 patients with stroke, 17 (22%) died within 30 days, and another 26 (32%) were disabled by hospital discharge or 30 days, whichever came first. Higher heart rate was the most important baseline clinical predictor of nonhemorrhagic stroke, followed by older age, prior anterior myocardial infarction, prior stroke or transient ischemic attack, and diabetes mellitus. These factors were used to develop a simple scoring nomogram that can predict the risk of nonhemorrhagic stroke. CONCLUSIONS: Stroke was an uncommon event in patients with acute coronary syndromes in the PURSUIT trial. These strokes are, however, associated with substantial morbidity and mortality rates. The majority of strokes were of nonhemorrhagic causes. Eptifibatide was not associated with an increase in intracranial hemorrhage, and no significant effect on nonhemorrhagic stroke was observed. We developed a useful nomogram for assigning baseline nonhemorrhagic stroke risk in this patient population.

Complications of transvenous right ventricular endomyocardial biopsy in adult patients with cardiomyopathy: a seven-year survey of 546 consecutive diagnostic procedures in a tertiary referral center.

To determine the incidence, nature and subsequent management of complications occurring during right ventricular endomyocardial biopsy in patients with cardiomyopathy, all events occurring during 546 procedures in 464 consecutive patients were prospectively recorded. The internal jugular vein was the primary site of introduction in 96% of cases. A total of 33 complications (6%) occurred: 15 (2.7%) during catheter insertion including 12 arterial punctures (2%), 2 vasovagal reactions (0.4%) and 1 episode of prolonged bleeding (0.2%), all without sequelae; 18 (3.3%) during biopsy included 6 arrhythmias (1.1%), 5 conduction abnormalities (1%), 4 possible perforations (0.7%) and 3 definite perforations (0.5%) (pericardial fluid). Two (0.4%) of the three patients with a perforation died. There was no secular trend in the complication rate, nor were complications associated with specific clinical or hemodynamic characteristics. It is concluded that the overall rate of endomyocardial biopsy complications (6%) is low, but mortality may occur.

Which angiographic variable best describes functional status 6 months after successful single-vessel coronary balloon angioplasty?

OBJECTIVES: The aim of this study was to determine which quantitative angiographic variable best describes functional status 6 months after coronary balloon angioplasty. BACKGROUND: Several angiographic restenosis criteria have been developed. These can be divided into those that describe the change in lesion severity and those that merely describe lesion severity at follow-up angiography. The functional significance of these criteria is unknown. METHODS: We studied 350 patients with single-vessel coronary artery disease who underwent a single-site balloon dilation. Sensitivity and specificity curves were constructed for the prediction of anginal status and exercise electrocardiography of four quantitative angiographic variables that describe restenosis. The point of highest diagnostic accuracy for the variables was determined at the intersection of the sensitivity and specificity curves. Results of exercise electrocardiography were considered indicative for ischemia 6 months after angioplasty if horizontal or downsloping ST segment depression > or = 1 mm occurred. RESULTS: The points of highest diagnostic accuracy of the angiographic variables were similar for both anginal status and exercise electrocardiography: 1.45 and 1.46 mm for the minimal lumen diameter measurements, 45.5% and 46.5% for the percent diameter stenosis measurements at follow-up, -0.30 and -0.32 mm for change in minimal lumen diameter and -10% and -10% for the change in percent diameter stenosis at follow-up. CONCLUSIONS: Angiographic variables reflecting a change in lesion severity at follow-up angiography were only slightly less accurate than variables that describe lesion severity at follow-up. The large study group and the fact that the same optimal values for diagnostic accuracy of the various quantitative angiographic variables were obtained for the prediction of two different markers of ischemia suggests that these values reflect the lesion severity or increase in lesion severity in major epicardial vessels at which coronary flow reserve is unable to meet myocardial demands.

Long-term follow-up after surgical closure of ventricular septal defect in infancy and childhood.

OBJECTIVES: The purpose of this study was to assess the health-related quality of life of patients who underwent surgical closure of a ventricular septal defect at a young age between 1968 and 1980. BACKGROUND: Since the beginning of open heart surgery for congenital cardiac malformations, the surgical techniques have continually improved. As a result, even infants have become eligible for surgical repair. Long-term follow-up data are not available on the health-related quality of life of nonselected patients after surgical repair at a young age. We therefore conducted a follow-up study of 176 infants and children consecutively operated on in one institution between 1968 and 1980. METHODS: Patients who were alive and could be traced through the offices of local registrars received an invitation to participate in the follow-up study, consisting of an interview, physical examination, echocardiography, exercise testing and standard 12-lead and 24-h electrocardiography. RESULTS: One hundred nine patients (78% of those eligible for follow-up) participated. The mean interval after operation (+/- SD) was 14.5 +/- 2.6 years. Eighty-four percent of the patients assessed their health as good or very good, and 89% had been free of any medical or surgical intervention since the operation. At physical examination all patients were in good health. Their mean exercise capacity was 100 +/- 17% (range 56% to 141%) of predicted values; 84% of the patients had a normal exercise capacity. Echocardiography demonstrated a small residual ventricular septal defect in seven patients (6%). There were no signs of pulmonary hypertension. No patient had symptomatic arrhythmias. CONCLUSIONS: Long-term results of surgical closure of ventricular septal defect in infancy and childhood are good. Pulmonary hypertension is absent. Personal health assessment is comparable to that of the normal population, as is exercise capacity, even though many patients have anatomic, hemodynamic or electrophysiologic sequelae.