Marco C. Post

Contemporary prevalence of pulmonary arterial hypertension in adult congenital heart disease following the updated clinical classification

BACKGROUND The aging congenital heart disease (CHD) population is prone to develop a variety of sequelae, including pulmonary arterial hypertension (PAH). Previous prevalence estimates are limited in applicability due to the use of tertiary centers, or database encoding only. We aimed to investigate the contemporary prevalence of PAH in adult CHD patients, using a nationwide population. METHODS A cross-sectional study was performed, using the population-based Dutch CONgenital CORvitia (CONCOR) registry. All patients born with a systemic-to-pulmonary shunt, thereby at risk of developing PAH, were identified. From this cohort, a random sample was obtained and carefully reviewed. RESULTS Of 12,624 registered adults with CHD alive in 2011, 5,487 (44%) were at risk of PAH. The random sample consisted of 1,814 patients (mean age 40 ± 15 years) and 135 PAH cases were observed. PAH prevalence in patients born with a systemic-to-pulmonary shunt was 7.4%. The prevalence of PAH after corrective cardiac surgery was remarkably high (5.7%). Furthermore, PAH prevalence increased with age, from 2.5% under 30 years until 35% in the eldest. PAH prevalence in the entire CHD population was 3.2%. Based on 3000 per million adult CHD patients in the general population, we can assume that PAH-CHD is present in 100 per million. CONCLUSIONS This new approach using a nationwide CHD population reports a PAH prevalence of 3.2% in CHD patients, and 100 per million in the general adult population. Especially in patients after shunt closure and the elderly, physicians should be aware of PAH-CHD, to provide optimal therapeutic and clinical care.

Assessment of Valvular Disorders in Survivors of Hodgkin's Lymphoma Treated by Mediastinal Radiotherapy ± Chemotherapy.

As the number of Hodgkins lymphoma (HL) survivors grows, understanding long-term complications becomes more important. Mediastinal radiotherapy (MRT) seems to cause valvular disease, and the prevalence might increase during follow-up. In this cross-sectional study 82 HL survivors participated (52% men, mean age 47.8 years, 50 treated with MRT). Valvular disease was diagnosed by transthoracic echocardiography and compared between HL survivors treated with and without MRT. Univariate and multivariate logistic regression analysis was used to identify predictors for valvular disease. During a median follow-up of 13.4 years (range 2 to 39 years), ≥ mild valvular disease was present in 61.2% of HL survivors with MRT (n = 30), compared with 31.0% of HL survivors without MRT (n = 9; odds ratio [OR] 3.51, 95% CI 1.32 to 9.30, p = 0.01). In multivariate analysis, only current age remained predictive for ≥ mild valvular disease (OR 1.08 per year, 95% CI 1.01 to 1.14, p = 0.023). Aortic regurgitation (AR) was most prevalent and irradiated patients had significantly more ≥ mild AR (38.2% vs 6.8%, p = 0.007). Within the MRT subgroup, time after radiation of >15 years was associated with AR (OR 4.70, 95% CI 1.05 to 21.03, p = 0.043), after adjusting for current age and hypertension. Severe valvular disease was present in 24.5% of HL survivors with MRT compared with 3.4% without MRT (p = 0.016). Valvular surgery was performed in 9 HL survivors (18.0%) with MRT and in none without MRT. In conclusion, the prevalence of valvular disease in HL survivors treated with MRT is high and increases with time after irradiation. Long-time screening for valvular disease by transthoracic echocardiography might be worthwhile.

Congenital valvular aortic stenosis in young adults: Predictors for rate of progression of stenosis and aortic dilatation

BACKGROUND Congenital aortic stenosis (AS) is the most common obstructive left-sided cardiac lesion in young adults, however little is known about the progression in adults. Therefore, we aimed to evaluate the progression rate of AS and aortic dilatation in a large multicenter retrospective cohort of asymptomatic young adults with congenital valvular AS. METHODS Data were obtained from chart abstraction. Linear mixed-effects models were used to evaluate the progression of AS and aortic dilatation over time. A joint model combining longitudinal echocardiographic and survival data was used for survival analysis. RESULTS A total of 414 patients (age 29 ± 10 years, 68% male) were included. Median follow-up duration was 4.1 (2.5-5.1) years (1587 patient-years). Peak aortic velocity was 3.4 ± 0.7 m/s at baseline and did not change over time in the total patient population (-0.01 ± 0.03 m/s/year). Increased left ventricular mass was significantly associated with faster AS progression (p<0.001). Aortic dilatation was present in 34% at baseline and 48% at follow-up (p<0.001). The aortic diameter linearly increased over time with a rate of 0.7 ± 0.2mm/year. Rate of aortic dissection was 0.06% per patient-year. Seventy patients required an aortic valve intervention (4.4% per patient-year), with AS progression rate as most powerful predictor (HR 5.11 (95% CI 3.47-7.53)). CONCLUSIONS In the majority of patients with mild-to-moderate congenital AS, AS severity does not progress over time. However patients with left ventricular hypertrophy are at risk for faster progression and should be monitored carefully. Although aortic dissections rarely occur, aortic dilatation is common and steadily progresses over time, warranting serial aortic imaging.

Pulmonary artery diameter to predict pulmonary hypertension in pulmonary sarcoidosis

Pulmonary hypertension (PH) is a known complication of pulmonary sarcoidosis with a prevalence ranging from 5% to 74% [1]. The aetiology of PH in sarcoidosis is not fully understood. Usually, it is attributed to the destruction of the distal capillary bed by lung fibrosis and/or chronic hypoxaemia. However, the severity of PH does not correlate consistently with the degree of pulmonary fibrosis, and PH exists in sarcoidosis patients without fibrosis, suggesting a multifactorial mechanism. The presence of PH is associated with a poor prognosis, and early diagnosis and treatment might improve outcome [1]. Echocardiography should always be performed when PH is suspected [2]. However, the accuracy of echocardiography in patients with interstitial lung diseases is often limited due to poor image quality and unreliable tricuspid regurgitation signal to measure the right ventricular systolic pressure (RVSP) [3]. Further invasive investigation with the gold standard, right heart catheterisation (RHC), is often required. In order to optimise the noninvasive diagnostic approach, there is a need for more accurate predictors of PH. Computed tomography (CT) may raise suspicion of PH in symptomatic patients or those examined for unrelated indications by showing an increased pulmonary artery (PA) diameter (≥29 mm) and PA diameter/ascending aorta diameter (AAD) ratio (≥1.0) [2]. Similarly, PA diameter indexed to body surface area (BSA) has been suggested as possible predictor of PH. However, these parameters have never been investigated in pulmonary sarcoidosis specifically. Pulmonary artery indexed for body surface area is the most accurate predictor for PH on CT in pulmonary sarcoidosis http://ow.ly/T863m

Screening children for pulmonary arteriovenous malformations: Evaluation of 18 years of experience

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant disease with multi‐systemic vascular dysplasia. Early diagnosis through screening is important to prevent serious complications. How best to screen children of affected parents for pulmonary arteriovenous malformations (PAVMs) is often subject to debate. Transthoracic contrast echocardiogram (TTCE) is considered optimal in screening for PAVMs in adults. Guidelines for the screening of children are not specific, reflecting the lack of scientific evidence on the best method to use.

Survival After MitraClip Treatment Compared to Surgical and Conservative Treatment for High-Surgical-Risk Patients With Mitral Regurgitation

Background— Survival outcome after MitraClip treatment, compared with surgical or conservative treatment, is not well defined. We examined survival after MitraClip treatment in a large multicenter real-life setting. Methods and Results— We retrospectively formed matched high-risk surgically and conservatively treated control cohorts to compare to a high-risk MitraClip cohort. One thousand thirty-six patients were included in 4 Dutch centers, of which 568 were treated with the MitraClip. The observed survival at 5-year follow-up in our MitraClip cohort was low (39.8%) but was comparable to our conservative cohort (40.5%). Observed 5-year survival for our surgical cohort was 76.3%. However, there were significant differences between the baseline characteristics of the 3 studied cohorts, with the MitraClip cohort having the highest comorbidity burden. After adjusting for baseline differences by using Cox regression, the MitraClip and surgical cohorts showed similar survival ratios (hazard ratio, 0.92; 95% confidence interval, 0.67–1.26; P=0.609), whereas both showed a lower mortality hazard when compared with conservative treatment (hazard ratio, 0.61; 95% confidence interval, 0.49–0.77; P<0.001 and hazard ratio, 0.56; 95% confidence interval, 0.42–0.76; P<0.001, respectively). Conclusions— This matched analysis suggests a lower mortality hazard for MitraClip intervention in a high-risk population with symptomatic mitral regurgitation when compared with conservative management alone.

Chance of surgery in adult congenital heart disease

Background Young patients with congenital heart disease reaching adulthood face mandatory transition to adult cardiology. Their new cardiologist needs to assess the chances of major future events such as surgery. Using a large national registry, we assessed if patient characteristics at the age of 18 years could predict the chance of congenital heart surgery in adulthood. Design and methods Of 10,300 patients from the CONCOR national registry, we used general patient characteristics at age 18 years, underlying congenital heart defect, history of complications, and interventions in childhood as potential predictors of congenital heart surgery occurring from age 18 years up to age 40 and 60 years. Cox regression was used to calculate hazard ratios with 95% confidence intervals. Analyses were performed separately for all congenital heart surgery and for valvular surgery alone. Results Altogether 2427 patients underwent congenital heart surgery after age 18 years, 1389 of whom underwent valvular surgery. Underlying heart defect, male sex, multiple defects, childhood endocarditis, supraventricular arrhythmia, aortic complications and paediatric cardiovascular surgery, independently predicted adult congenital heart surgery. The mean chance of congenital heart surgery was 22% up to age 40 and 43% up to age 60 years; individual chances spanned from 9–68% up to age 40 and from 19–93% up to age 60 years. Conclusion At the time of transition from paediatric to adult cardiology, an easily obtainable set of characteristics of patients with congenital heart disease can meaningfully inform cardiologists about the patients individual chance of surgery in adulthood. Our findings warrant validation in other cohorts.

RV adaptation to increased afterload in congenital heart disease and pulmonary hypertension

Background The various conditions causing a chronic increase of RV pressure greatly differ in the occurrence of RV failure, and in clinical outcome. To get a better understanding of the differences in outcome, RV remodeling, longitudinal function, and transverse function are compared between patients with pulmonary stenosis (PS), those with a systemic RV and those with pulmonary hypertension (PH). Materials and methods This cross-sectional study prospectively enrolled subjects for cardiac magnetic resonance imaging (CMR), functional echocardiography and cardiopulmonary exercise testing. The study included: controls (n = 37), patients with PS (n = 15), systemic RV (n = 19) and PH (n = 20). Statistical analysis was performed using Analysis of Variance (ANOVA) with posthoc Bonferroni. Results PS patients had smaller RV volumes with higher RV ejection fraction (61.1±9.6%; p<0.05) compared to controls (53.8±4.8%). PH and systemic RV patients exhibited dilated RVs with lower RV ejection fraction (36.9±9.6% and 46.3±10.1%; p<0.01 versus controls). PH patients had lower RV stroke volume (p = 0.02), RV ejection fractions (p<0.01) and VO2 peak/kg% (p<0.001) compared to systemic RV patients. Mean apical transverse RV free wall motion was lower and RV free wall shortening (p<0.001) was prolonged in PH patients–resulting in post-systolic shortening and intra-ventricular dyssynchrony. Apical transverse shortening and global longitudinal RV deformation showed the best correlation to RV ejection fraction (respectively r = 0.853, p<0.001 and r = 0.812, p<0.001). Conclusions RV remodeling and function differed depending on the etiology of RV pressure overload. In contrast to the RV of patients with PS or a systemic RV, in whom sufficient stroke volumes are maintained, the RV of patients with PH seems unable to compensate for its increase in afterload completely. Key mediators of RV dysfunction observed in PH patients, were: prolonged RV free wall shortening, resulting in post-systolic shortening and intra-ventricular dyssynchrony, and decreased transverse function.

Pulmonary Arterial Hypertension and Hereditary Haemorrhagic Telangiectasia

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant inherited disease characterised by multisystemic vascular dysplasia. Heritable pulmonary arterial hypertension (HPAH) is a rare but severe complication of HHT. Both diseases can be the result of genetic mutations in ACVLR1 and ENG encoding for proteins involved in the transforming growth factor-beta (TGF-β) superfamily, a signalling pathway that is essential for angiogenesis. Changes within this pathway can lead to both the proliferative vasculopathy of HPAH and arteriovenous malformations seen in HHT. Clinical signs of the disease combination may not be specific but early diagnosis is important for appropriate treatment. This review describes the molecular mechanism and management of HPAH and HHT.

Biological versus mechanical heart valve prosthesis during pregnancy in women with congenital heart disease

BACKGROUND We evaluate pregnancy outcome and anticoagulation regimes in women with mechanical and biological prosthetic heart valves (PHV) for congenital heart disease. METHODS Retrospective multicenter cohort studying pregnancy outcomes in an existing cohort of patients with PHV. RESULTS 52 women had 102 pregnancies of which 78 pregnancies (46 women) ≥20 weeks duration (59 biological, 19 mechanical PHV). Miscarriages (n = 19, ≤20 weeks) occurred more frequently in women using anticoagulation (P < .05). During 42% of pregnancies of women with mechanical PHV a combined low molecular weight heparin (LMWH) vitamin-K-antagonist anticoagulation regime was used (n = 8). Overall, cardiovascular, obstetric and fetal/neonatal complications occurred in 17% (n = 13), 68% (n = 42) and 42% (n = 27) of the pregnancies. Women with mechanical PHV had significantly higher cardiovascular (12% vs 32%, P < .05), obstetric (59% vs 85%, P = .02) and fetal/neonatal (34% vs 61%, P < .05) complication rates than women with biological PHV. This was related to PHV thrombosis (n = 3, P < .02), post-partum hemorrhage (P < .02), cesarean section (P < .02), low birth weight and small for gestational age (both P < .05). PHV thrombosis occurred in 3 pregnancies, including 2/5 pregnancies with pulmonary mechanical PHV. PHV thrombosis was related to necessary cessation of anticoagulation therapy or insufficient monitoring of LMWH. Other cardiovascular complications occurred equally frequent in both groups. CONCLUSION Complications occur more often in pregnancies of women with a mechanical PHV than in women with a biological PHV, mainly caused by PHV thrombosis and bleeding complications. Meticulous monitoring of anticoagulation in pregnant women is necessary. Women with a pulmonary mechanical PHV are at high risk of complications.