Arie P.J. van Dijk

Preoperative Thresholds for Pulmonary Valve Replacement in Patients With Corrected Tetralogy of Fallot Using Cardiovascular Magnetic Resonance

Background— To facilitate the optimal timing of pulmonary valve replacement, we analyzed preoperative thresholds of right ventricular (RV) volumes above which no decrease or normalization of RV size takes place after surgery. Methods and Results— Between 1993 and 2006, 71 adult patients with corrected tetralogy of Fallot underwent pulmonary valve replacement in a nationwide, prospective follow-up study. Patients were evaluated with cardiovascular magnetic resonance both preoperatively and postoperatively. Changes in RV volumes were expressed as relative change from baseline. RV volumes decreased with a mean of 28%. RV ejection fraction did not change significantly after surgery (from 42±10% to 43±10%; P=0.34). Concomitant RV outflow tract reduction resulted in a 25% larger decrease of RV volumes. After correction for surgical RV outflow tract reduction, higher preoperative RV volumes (mL/m2) were independently associated with a larger decrease of RV volumes (RV end-diastolic volume: &bgr;=0.41; P<0.001). Receiver operating characteristic analysis revealed a cutoff value of 160 mL/m2 for normalization of RV end-diastolic volume or 82 mL/m2 for RV end-systolic volume. Conclusions— Overall, we could not find a threshold above which RV volumes did not decrease after surgery. Preoperative RV volumes were independently associated with RV remodeling and also when corrected for a surgical reduction of the RV outflow tract. However, normalization could be achieved when preoperative RV end-diastolic volume was <160 mL/m2 or RV end-systolic volume was <82 mL/m2.

Mortality in adult congenital heart disease

AIMS Mortality in adults with congenital heart disease is known to be increased, yet its extent and the major mortality risks are unclear. METHODS AND RESULTS The Dutch CONCOR national registry for adult congenital heart disease was linked to the national mortality registry. Coxs regression was used to assess mortality predictors. Of 6933 patients, 197 (2.8%) died during a follow-up of 24 865 patient-years. Compared with the general national population, there was excess mortality, particularly in the young. Median age at death was 48.8 years. Of all deaths, 77% had a cardiovascular origin; 45% were due to chronic heart failure (26%, age 51.0 years) or sudden death (19%, age 39.1 years). Age predicted mortality, as did gender, severity of defect, number of interventions, and number of complications [hazard ratio (HR) range 1.1-5.9, P < 0.05]. Several complications predicted all-cause mortality beyond the effects of age, gender, and congenital heart disease severity, i.e. endocarditis, supraventricular arrhythmias, ventricular arrhythmias, conduction disturbances, myocardial infarction, and pulmonary hypertension (HR range 1.4-3.1, P < 0.05). These risks were similar in patients above and below 40 years of age. Almost all complications predicted death due to heart failure (HR range 2.0-5.1, P < 0.05); conduction disturbances and pulmonary hypertension predicted sudden death (HR range 2.0-4.7, P < 0.05). CONCLUSION Mortality is increased in adults with congenital heart disease, particularly in the young. The vast majority die from cardiovascular causes. Mortality risk, particularly by heart failure, is increased by virtually all complications. Complications are equally hazardous in younger as in older patients.

Predictors of pregnancy complications in women with congenital heart disease

AIMS Data regarding pregnancy outcome in women with congenital heart disease (CHD) are limited. METHODS AND RESULTS In 1802 women with CHD, 1302 completed pregnancies were observed. Independent predictors of cardiac, obstetric, and neonatal complications were calculated using logistic regression. The most prevalent cardiac complications during pregnancy were arrhythmias (4.7%) and heart failure (1.6%). Factors independently associated with maternal cardiac complications were the presence of cyanotic heart disease (corrected/uncorrected) (P < 0.0001), the use of cardiac medication before pregnancy (P < 0.0001), and left heart obstruction (P < 0.0001). New characteristics were mechanical valve replacement (P = 0.0014), and systemic (P = 0.04) or pulmonary atrioventricular valve regurgitation related with the underlying (moderately) complex CHD (P = 0.03). A new risk score for cardiac complications is proposed. The most prevalent obstetric complications were hypertensive complications (12.2%). No correlation of maternal characteristics with adverse obstetric outcome was found. The most prevalent neonatal complications were premature birth (12%), small for gestational age (14%), and mortality (4%). Cyanotic heart disease (corrected/uncorrected) (P = 0.0003), mechanical valve replacement (P = 0.03), maternal smoking (P = 0.007), multiple gestation (P = 0.0014), and the use of cardiac medication (P = 0.0009) correlated with adverse neonatal outcome. CONCLUSION In our tertiary CHD cohort, cardiac, obstetric, and neonatal complications were frequently encountered, and (new) correlations of maternal baseline data with adverse outcome are reported. A new risk score for adverse cardiac complications is proposed, although prospective validation remains necessary.

Evaluating the systemic right ventricle by CMR: the importance of consistent and reproducible delineation of the cavity

BackgroundThe method used to delineate the boundary of the right ventricle (RV), relative to the trabeculations and papillary muscles in cardiovascular magnetic resonance (CMR) ventricular volume analysis, may matter more when these structures are hypertrophied than in individuals with normal cardiovascular anatomy. This study aimed to compare two methods of cavity delineation in patients with systemic RV.MethodsTwenty-nine patients (mean age 34.7 ± 12.4 years) with a systemic RV (12 with congenitally corrected transposition of the great arteries (ccTGA) and 17 with atrially switched (TGA) underwent CMR. We compared measurements of systemic RV volumes and function using two analysis protocols. The RV trabeculations and papillary muscles were either included in the calculated blood volume, the boundary drawn immediately within the apparently compacted myocardial layer, or they were manually outlined and excluded. RV stroke volume (SV) calculated using each method was compared with corresponding left ventricular (LV) SV. Additionally, we compared the differences in analysis time, and in intra- and inter-observer variability between the two methods. Paired samples t-test was used to test for differences in volumes, function and analysis time between the two methods. Differences in intra- and inter-observer reproducibility were tested using an extension of the Bland-Altman method.ResultsThe inclusion of trabeculations and papillary muscles in the ventricular volume resulted in higher values for systemic RV end diastolic volume (mean difference 28.7 ± 10.6 ml, p < 0.001) and for end systolic volume (mean difference 31.0 ± 11.5 ml, p < 0.001). Values for ejection fraction were significantly lower (mean difference -7.4 ± 3.9%, p < 0.001) if structures were included. LV SV did not differ significantly from RV SV for both analysis methods (p = NS). Including structures resulted in shorter analysis time (p < 0.001), and showed better inter-observer reproducibility for ejection fraction (p < 0.01).ConclusionThe choice of method for systemic RV cavity delineation significantly affected volume measurements, given the CMR acquisition and analysis systems used. We recommend delineation outside the trabeculations for routine clinical measurements of systemic RV volumes as this approach took less time and gave more reproducible measurements.

Prospective cardiopulmonary screening program to detect chronic thromboembolic pulmonary hypertension in patients after acute pulmonary embolism

Background Chronic thromboembolic pulmonary hypertension after pulmonary embolism is associated with high morbidity and mortality. Understanding the incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism is important for evaluating the need for screening but is also a subject of debate because of different inclusion criteria among previous studies. We determined the incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism and the utility of a screening program for this disease. Design and Methods We conducted a cohort screening study in an unselected series of consecutive patients (n=866) diagnosed with acute pulmonary embolism between January 2001 and July 2007. All patients who had not been previously diagnosed with pulmonary hypertension (PH) and had survived until study inclusion were invited for echocardiography. Patients with echocardiographic suspicion of PH underwent complete work-up for chronic thromboembolic pulmonary hypertension, including ventilation-perfusion scintigraphy and right heart catheterization. Results After an average follow-up of 34 months of all 866 patients, PH was diagnosed in 19 patients by routine clinical care and in 10 by our screening program; 4 patients had chronic thromboembolic pulmonary hypertension, all diagnosed by routine clinical care. The cumulative incidence of chronic thromboembolic pulmonary hypertension after all cause pulmonary embolism was 0.57% (95% confidence interval [CI] 0.02–1.2%) and after unprovoked pulmonary embolism 1.5% (95% CI 0.08–3.1%). Conclusions Because of the low incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism and the very low yield of the echocardiography based screening program, wide scale implementation of prolonged follow-up including echocardiography of all patients with pulmonary embolism to detect chronic thromboembolic pulmonary hypertension does not seem to be warranted.

Effect of Valsartan on Systemic Right Ventricular Function A Double-Blind, Randomized, Placebo-Controlled Pilot Trial

Background— The role of angiotensin II receptor blockers in patients with a systemic right ventricle has not been elucidated. Methods and Results— We conducted a multicenter, double-blind, parallel, randomized controlled trial of angiotensin II receptor blocker valsartan 160 mg twice daily compared with placebo in patients with a systemic right ventricle caused by congenitally or surgically corrected transposition of the great arteries. The primary end point was change in right ventricular ejection fraction during 3-year follow-up, determined by cardiovascular magnetic resonance imaging or, in patients with contraindication for magnetic resonance imaging, multirow detector computed tomography. Secondary end points were change in right ventricular volumes and mass, ![Graphic][1] peak, and quality of life. Primary analyses were performed on an intention-to-treat basis. A total of 88 patients (valsartan, n=44; placebo, n=44) were enrolled in the trial. No serious adverse effects occurred in either group. There was no significant effect of 3-year valsartan therapy on systemic right ventricular ejection fraction (treatment effect, 1.3%; 95% confidence interval, −1.3% to 3.9%; P =0.34), maximum exercise capacity, or quality of life. There was a larger increase in right ventricular end-diastolic volume (15 mL; 95% confidence interval, 3–28 mL; P <0.01) and mass (8 g; 95% confidence interval, 2–14 g; P =0.01) in the placebo group than in the valsartan group. Conclusions— There was no significant treatment effect of valsartan on right ventricular ejection fraction, exercise capacity, or quality of life. Valsartan was associated with a similar frequency of significant clinical events as placebo. Small but significant differences between valsartan and placebo were present for change in right ventricular volumes and mass. Clinical Trial Registration— URL: . Unique identifier: [ISRCTN52352170][2]. # Clinical Perspective {#article-title-47} [1]: /embed/inline-graphic-1.gif [2]: /external-ref?link_type=ISRCTN&access_num=ISRCTN52352170Background— The role of angiotensin II receptor blockers in patients with a systemic right ventricle has not been elucidated. Methods and Results— We conducted a multicenter, double-blind, parallel, randomized controlled trial of angiotensin II receptor blocker valsartan 160 mg twice daily compared with placebo in patients with a systemic right ventricle caused by congenitally or surgically corrected transposition of the great arteries. The primary end point was change in right ventricular ejection fraction during 3-year follow-up, determined by cardiovascular magnetic resonance imaging or, in patients with contraindication for magnetic resonance imaging, multirow detector computed tomography. Secondary end points were change in right ventricular volumes and mass, peak, and quality of life. Primary analyses were performed on an intention-to-treat basis. A total of 88 patients (valsartan, n=44; placebo, n=44) were enrolled in the trial. No serious adverse effects occurred in either group. There was no significant effect of 3-year valsartan therapy on systemic right ventricular ejection fraction (treatment effect, 1.3%; 95% confidence interval, −1.3% to 3.9%; P=0.34), maximum exercise capacity, or quality of life. There was a larger increase in right ventricular end-diastolic volume (15 mL; 95% confidence interval, 3–28 mL; P<0.01) and mass (8 g; 95% confidence interval, 2–14 g; P=0.01) in the placebo group than in the valsartan group. Conclusions— There was no significant treatment effect of valsartan on right ventricular ejection fraction, exercise capacity, or quality of life. Valsartan was associated with a similar frequency of significant clinical events as placebo. Small but significant differences between valsartan and placebo were present for change in right ventricular volumes and mass. Clinical Trial Registration— URL: http://www.controlled-trials.com. Unique identifier: ISRCTN52352170.

Patient outcomes after acute pulmonary embolism. A pooled survival analysis of different adverse events.

RATIONALE There is a lack of information on the long-term prognosis of patients with acute pulmonary embolism (PE). OBJECTIVES To assess the long-term risk for adverse events after PE. METHODS Consecutive patients diagnosed with PE between January 2001 and July 2007, and patients in whom PE was ruled out from a previous study were followed until July 2008 for the occurrence of adverse clinical events: mortality, symptomatic recurrent venous thromboembolism, cancer, arterial cardiovascular events and chronic thromboembolic pulmonary hypertension. Hazard ratios (HR) for all endpoints and a combined endpoint were calculated and adjusted for potential confounders. MEASUREMENTS AND MAIN RESULTS Three hundred eight patients with unprovoked, 558 with provoked, and 334 without PE were studied with a median follow-up period of 3.3 years. Patients with unprovoked PE had a lower overall risk for mortality than patients with provoked PE (HR, 0.59; 95% confidence interval [CI], 0.43-0.82), but a higher risk for nonmalignancy-related mortality (HR, 1.8; 95% CI, 1.3-2.5), recurrent venous thromboembolism (HR, 2.1; 95% CI, 1.3-3.1), cancer (HR, 4.4; 95% CI, 2.0-10), cardiovascular events (HR, 2.6; 95% CI, 1.5-3.8) and chronic thromboembolic pulmonary hypertension (1.5 vs. 0%). The risk for the combined endpoint did not differ between both groups (HR, 0.98; 95% CI, 0.82-1.1). Patients without PE had similar risks for malignancy and cardiovascular events than patients with provoked PE, but lower risks for the remaining outcomes. The fraction of both patients with provoked and unprovoked PE without events after 1 year was only 70% and decreased to fewer than 60% after 2 years and fewer than 50% after 4 years, whereas this latter was 84% for the control patients. CONCLUSIONS The clinical course of acute PE is complicated by high rates of serious adverse events, which occur in half of the patients within 4 years.

Effect of bosentan on exercise capacity and quality of life in adults with pulmonary arterial hypertension associated with congenital heart disease with and without Down's syndrome

Pulmonary arterial hypertension associated with congenital heart disease caused by systemic-to-pulmonary shunting was associated with a high risk of morbidity and mortality. In this retrospective study, the longer term treatment effect of bosentan on exercise capacity and quality of life (QoL) were evaluated in 58 adult patients (>18 years) with pulmonary arterial hypertension associated with congenital heart disease, including patients with Downs syndrome. All patients were evaluated at baseline and during follow-up using laboratory tests, 6-minute walk test, QoL questionnaires, and Doppler echocardiography. Treatment efficacy was analyzed separately for patients without (n = 30) and with Downs syndrome (n = 28). Median follow-up of all patients treated with bosentan was 22 months (range 3 to 36). In patients without Downs syndrome, mean 6-minute walk distance increased from 427 +/- 97 to 461 +/- 104 m (p <0.01) after 6 months of treatment, followed by a gradual return to baseline and disease stabilization. QoL improved significantly during treatment and was maintained during 18 months of follow-up (p <0.05). In patients with Downs syndrome, 6-minute walk distance and QoL were stable during treatment. In conclusion, findings suggested that in patients without Downs syndrome, longer term bosentan treatment resulted in a persistent improvement in QoL and stabilization of exercise capacity.

Impact of bosentan on exercise capacity in adults after the Fontan procedure : a randomized controlled trial

An endothelin‐1 receptor blocker, shown to be effective in patients with pulmonary arterial hypertension, might decrease pulmonary vascular resistance to increase cardiac filling and consequently improve exercise capacity in Fontan patients.

Quality of Life in Long-term Survivors of Acute Pulmonary Embolism

BACKGROUND To our knowledge, studies evaluating the quality of life (QoL) in patients with a history of acute pulmonary embolism (PE) are not available, even though QoL is a key outcome component of medical care and a predictor of disease-specific prognosis. METHODS As part of a large follow-up study, the Short Form 36 (SF-36) was presented to consecutive patients who had survived one or more episodes of acute PE. The results of all nine subscales of the SF-36 were compared with sex- and age-adjusted Dutch population norms. Single and multivariate analyses were performed to identify independent determinants of the QoL in our study population. RESULTS The SF-36 was completed by 392 patients. Except for the health change subscale, patients had substantially lower QoL than population norms on all eight remaining subscales. After multivariate analysis, the time interval between the last thromboembolic episode and study inclusion was inversely related to QoL, and significant determinants of poor QoL were prior PE, age, obesity, active malignancy, and cardiopulmonary comorbid conditions. Regression models that included all identified significant determinants proved to be quite modest predictors for QoL in the individual patient. Awareness of illness, coping mechanisms, and self-management behavior might be additional important indicators of QoL in our study population but require further investigation. CONCLUSION We identified several PE- and non-PE-related determinants of QoL in patients with a history of acute PE, which is impaired compared with sex- and age-adjusted population norms. QoL after acute PE should be studied more extensively and added as a standard measure to outcome studies.