Family screening in patients with isolated bicuspid aortic valve : Restriction to those with aortic dilatation is not justified.

AIM: To determine the prevalence of undiagnosed bicuspid aortic valve (BAV) and isolated aortic dilatation in first-degree relatives (FDRs) of patients with isolated BAV and to explore the recurrence risk of BAV in different subgroups of probands with BAV. Recent American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines recommend family screening in patients with associated aortopathy only. METHODS: During follow-up visits, patients with isolated BAV received a printed invitation for their FDRs advising cardiac screening. RESULTS: From 2012-2019, 257 FDRs of 118 adult BAV patients were screened, among whom 63 (53%) index patients had undergone aortic valve surgery (AVS), including concomitant aortic replacement in 25 (21%). Of the non-operated index patients, 31 (26%) had aortic dilatation (> 40 mm). Mean age of the FDRs was 48 years (range 4-83) and 42% were male. The FDR group comprised 20 parents, 103 siblings and 134 offspring. Among these FDRs, 12 (4.7%) had a previously undiagnosed BAV and 23 (8.9%) had an isolated aortic dilatation. FDRs of the probands with previous AVS (n = 147) had a risk ratio for BAV of 2.25 (95% confidence interval (CI) 0.62-8.10). FDRs of the probands with BAV and repaired or unrepaired aortic dilatation (n = 127) had a risk ratio for BAV of 0.51 (95% CI 0.16-1.66). CONCLUSION: Screening FDRs of patients with isolated BAV resulted in a reasonable yield of 14% new cases of BAV or isolated aortic dilatation. A trend towards an increased risk of BAV in FDRs was observed in the probands with previous AVS, whereas this risk seemed to be diminished in the probands with associated aortic dilatation. This latter finding does not support the restrictive ACC/AHA recommendation.

The aortic root in repaired tetralogy of Fallot: Serial measurements and impact of losartan treatment.

BACKGROUND: Aortic root dilatation is common in adults with repaired tetralogy of Fallot (rTOF) and might lead to aortic dissection. However, little is known on progression of aortic dilatation and the effect of pharmaceutical treatment. This study aims to determine factors associated with aortic growth and investigate effects of losartan. METHODS AND RESULTS: We performed a prespecified analysis from the 1:1 randomized, double-blind REDEFINE trial. Aortic root diameters were measured at baseline and after 2.0 ± 0.3 years of follow-up using cardiovascular magnetic resonance (CMR) imaging. A total of 66 patients were included (68% men, age 40 ± 12 years, baseline aortic root 37 ± 6 mm, 32% aortic dilatation (>40 mm)). There was a trend towards slow aortic root growth (+0.6 ± 2.3 mm after two years, p = 0.06) (n = 60). LV stroke volume was the only factor associated with both a larger baseline aortic root (ß: 0.09 mm/ml (95% C.I.:0.02, 0.15), p = 0.010) and with aortic growth during follow-up (ß: 0.04 mm/ml (95% C.I.:0.005, 0.066), p = 0.024), after correction for age, sex, and body surface area using linear regression analysis. No treatment effect of losartan was found (p = 0.17). CONCLUSIONS: Aortic root dilatation was present in about one-third of rTOF patients. A larger LV stroke volume was associated with both a larger baseline aortic root and ongoing growth. Our findings provide no arguments for lower aortic diameter thresholds for prophylactic surgery compared to the general population.

New developments in adult congenital heart disease.

Congenital heart disease (CHD) affects 0.8% of live births and over the past decades technical improvements and large-scale repair has led to increased survival into adulthood of over 95% of the new-born. A new group of patients, those who survived their congenital heart defect, has emerged but late complications including heart failure, pulmonary hypertension (PH), arrhythmias, aneurysms and endocarditis appeared numerous, with a huge impact on mortality and morbidity. However, innovations over the past years have changed the landscape of adult CHD dramatically. In the diagnostic process important improvements have been made in the use of MRI, biomarkers, e­health concepts and 3D visualisation of anatomy. Care is now concentrated in specialised centres, with a continuous emphasis on education and the introduction of weekly multidisciplinary consultations on diagnosis and intervention. Surgery and percutaneous intervention have been refined and new concepts applied, further reducing the burden of the congenital malformations. Research has matured from case series to global networks. Currently, adults with CHD are still facing high risks of early mortality and morbidity. By global collaboration and continuous education and development and innovation of our diagnostic and therapeutic arsenal, we will improve the perspectives of these young patients.

Non-vitamin K antagonist oral anticoagulants (NOACs) for thromboembolic prevention, are they safe in congenital heart disease? Results of a worldwide study.

BACKGROUND: Current guidelines consider vitamin K antagonists (VKA) the oral anticoagulant agents of choice in adults with atrial arrhythmias (AA) and moderate or complex forms of congenital heart disease, significant valvular lesions, or bioprosthetic valves, pending safety data on non-VKA oral anticoagulants (NOACs). Therefore, the international NOTE registry was initiated to assess safety, change in adherence and quality of life (QoL) associated with NOACs in adults with congenital heart disease (ACHD). METHODS: An international multicenter prospective study of NOACs in ACHD was established. Follow-up occurred at 6 months and yearly thereafter. Primary endpoints were thromboembolism and major bleeding. Secondary endpoints included minor bleeding, change in therapy adherence (≥80% medication refill rate, ≥6 out of 8 on Morisky-8 questionnaire) and QoL (SF-36 questionnaire). RESULTS: In total, 530 ACHD patients (mean age 47 SD 15 years; 55% male) with predominantly moderate or complex defects (85%), significant valvular lesions (46%) and/or bioprosthetic valves (11%) using NOACs (rivaroxaban 43%; apixaban 39%; dabigatran 12%; edoxaban 7%) were enrolled. The most common indication was AA (91%). Over a median follow-up of 1.0 [IQR 0.0-2.0] year, thromboembolic event rate was 1.0% [95%CI 0.4-2.0] (n = 6) per year, with 1.1% [95%CI 0.5-2.2] (n = 7) annualized rate of major bleeding and 6.3% [95%CI 4.5-8.5] (n = 37) annualized rate of minor bleeding. Adherence was sufficient during 2 years follow-up in 80-93% of patients. At 1-year follow-up, among the subset of previous VKA-users who completed the survey (n = 33), QoL improved in 6 out of 8 domains (p ≪ 0.05). CONCLUSIONS: Initial results from our worldwide prospective study suggest that NOACs are safe and may be effective for thromboembolic prevention in adults with heterogeneous forms of congenital heart disease.

PREVENTION-ACHD: PRospEctiVE study on implaNTable cardioverter-defibrillator therapy and suddeN cardiac death in Adults with Congenital Heart Disease; Rationale and Design.

BACKGROUND: Many adult congenital heart disease (ACHD) patients are at risk of sudden cardiac death (SCD). An implantable cardioverter-defibrillator (ICD) may prevent SCD, but the evidence for primary prevention indications is still unsatisfactory. STUDY DESIGN: PREVENTION-ACHD is a prospective study with which we aim to prospectively validate a new risk score model for primary prevention of SCD in ACHD patients, as well as the currently existing guideline recommendations. Patients are screened using a novel risk score to predict SCD as well as current ICD indications according to an international Consensus Statement. Patients are followed up for two years. The primary endpoint is the occurrence of SCD and sustained ventricular arrhythmias. The Study was registered at ClinicalTrials.gov (NCT03957824). CONCLUSION: PREVENTION-ACHD is the first prospective study on SCD in ACHD patients. In the light of a growing and aging population of patients with more severe congenital heart defects, more robust clinical evidence on primary prevention of SCD is urgently needed.

Adults with congenital heart disease: ready for mobile health?

PURPOSE: Mobile health (mHealth) could improve the outcome of grown-up patients with congenital heart disease (GUCH) and reduce their emergency care utilisation. Inappropriate use of mHealth, however, can lead to data overload for professionals and unnecessary data collection for patients, increasing the burden for both. We aimed to determine the clinical characteristics of patients with high emergency care utilisation and to test whether these patients were willing to start using mHealth. METHODS: Clinical characteristics and emergency care utilisation of consecutive GUCH patients who visited one of the two participating cardiologists at the outpatient clinic of the Academic Medical Centre in Amsterdam were studied retrospectively. All patients were approached to fill in an mHealth questionnaire. A frequency of three or more emergency visits in 5 years was defined as high emergency care utilisation. RESULTS: In total, 202 consecutive GUCH patients who visited one of the two participating cardiologists were studied. Median age was 41 years, 47% were male, and 51% were symptomatic. In the previous 5 years, 134 emergency visits were identified. Of all patients, 8% had high emergency care utilisation. High emergency care utilisation was associated with patients being symptomatic, using antiarrhythmic drugs or diuretics. In total, 75% of all patients with high emergency care utilisation were willing to start using mHealth. CONCLUSION: GUCH patients who are symptomatic, those on antiarrhythmic drug therapy and those on diuretics are suitable candidates for enrolment in future mHealth initiatives because of both high care utilisation and high motivation to start using mHealth.

Maternal right ventricular function, uteroplacental circulation in first trimester and pregnancy outcome in women with congenital heart disease.

OBJECTIVE: Pregnant women with congenital heart disease (CHD) have an increased risk of abnormal uteroplacental flow, measured from the second trimester onwards, which is associated with pregnancy complications affecting the mother and the fetus. Maternal right ventricular (RV) dysfunction has been suggested as a predisposing factor for impaired uteroplacental flow in these women. The aim of this study was to investigate the association of first-trimester uteroplacental flow measurements with prepregnancy maternal cardiac function and pregnancy complications in women with CHD, with particular focus on the potential role of RV (dys)function. METHODS: This study included 138 pregnant women with CHD from the prospective ZAHARA III study (Zwangerschap bij Aangeboren HARtAfwijkingen; Pregnancy and CHD). Prepregnancy clinical and echocardiographic data were collected. Clinical evaluation, echocardiography (focused on RV function, as assessed by tricuspid annular plane systolic excursion (TAPSE)) and uterine artery (UtA) pulsatility index (PI) measurements were performed at 12, 20 and 32 weeks of gestation. Univariable and multivariable regression analyses were performed to assess the association between prepregnancy variables and UtA-PI during pregnancy. The association between UtA-PI at 12 weeks and cardiovascular, obstetric and neonatal complications was also assessed. RESULTS: On multivariable regression analysis, prepregnancy TAPSE was associated negatively with UtA-PI at 12 weeks of gestation (ß = -0.026; P = 0.036). Women with lower prepregnancy TAPSE (≤ 20 mm vs > 20 mm) had higher UtA-PI at 12 weeks (1.5 ± 0.5 vs 1.2 ± 0.6; P = 0.047). Increased UtA-PI at 12 weeks was associated with obstetric complications (P = 0.003), particularly hypertensive disorders (pregnancy-induced hypertension and pre-eclampsia, P = 0.019 and P = 0.026, respectively). CONCLUSIONS: In women with CHD, RV dysfunction before pregnancy seems to impact placentation, resulting in increased resistance in UtA flow, which is detectable as early as in the first trimester. This, in turn, is associated with pregnancy complications. Early monitoring of uteroplacental flow might be of value in women with CHD with pre-existing subclinical RV dysfunction to identify pregnancies that would benefit from close obstetric surveillance. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

First real-world experience with mobile health telemonitoring in adult patients with congenital heart disease.

BACKGROUND: Arrhythmias and heart failure are common and invalidating sequelae in adult patients with congenital heart disease (CHD). Mobile health (m-Health) enables daily monitoring and a timely response that might prevent deterioration. We present an observational prospective registry to evaluate feasibility of an m­Health telemonitoring program for managing arrhythmia, heart failure and blood pressure in symptomatic adults with CHD. METHODS: Symptomatic adult patients with CHD are enrolled in an m­Health telemonitoring program, which evaluates single-lead ECG, blood pressure and weight measurements. In case of symptoms extra measurements could be performed. Data are collected by mobile apps, matched with individualised thresholds. Patients are contacted if thresholds were exceeded or if arrhythmias were found, for treatment adjustments or reassurance. Data on emergency care utilisation, hospitalisation and patient-reported outcome measures are used to assess quality of life and self-management. RESULTS: 129 symptomatic CHD patients were invited to participate, 55 participated. Reasons for refusing consent included too time consuming to participate in research (30) and to monitor vital signs (14). At baseline 22 patients were in New York Heart Association class ≥ II heart failure, 43 patients had palpitations or documented arrhythmias, and 8 had hypertension. Mean follow-up was 3.0 months, one patient dropped out, and adherence was 97%. CONCLUSION: The first results indicate that this program is feasible with high adherence.

Differences at surgery between patients with bicuspid and tricuspid aortic valves.

AIM: To determine differences in surgical procedures and clinical characteristics at the time of surgery between native bicuspid aortic valves (BAV) and tricuspid aortic valves (TAV) in patients being followed up after aortic valve surgery (AVS). METHODS: In this retrospective cohort study in a non-academic hospital, we identified patients who had a surgeon's report of the number of native valve cusps and were still being followed up. We selected patients with BAV and TAV, and used multivariable regression analyses to identify associations between BAV-TAV and pre-specified clinical characteristics. RESULTS: Of 439 patients, 140 had BAV (32%) and 299 TAV (68%). BAV patients were younger at the time of surgery (mean age 58.6 ± 13 years) than TAV patients (69.1 ± 12 years, p < 0.001) and were more often male (64% vs 53%; p = 0.029). Cardiovascular risk factors were less prevalent in BAV than in TAV patients at the time of surgery (hypertension (31% vs 55%), hypercholesterolaemia (29% vs 58%) and diabetes (7% vs 16%); all p < 0.005). Concomitant coronary artery bypass grafting (CABG) was performed less often in BAV than in TAV patients (14% vs 39%, p < 0.001), even when adjusted for confounders (adjusted odds ratio (adj.OR) 0.45; 95% CI: 0.25-0.83). In contrast, surgery of the proximal aorta was performed more often (31% vs 11%, respectively, p < 0.001; adj.OR 2.3; 95% CI: 1.3-4.0). CONCLUSIONS: Whereas mechanical stress is the supposed major driver of valvulopathy towards AVS in BAV, prevalent cardiovascular risk factors are a suspected driver towards the requirement for AVS and concomitant CABG in TAV, an observation based on surgical determination of the number of valve cusps.

Oral anticoagulant therapy in adults with congenital heart disease and atrial arrhythmias: Implementation of guidelines.

BACKGROUND: Current guidelines on oral anticoagulation (OAC) in adults with congenital heart disease (ACHD) and atrial arrhythmias (AA) consist of heterogeneous and divergent recommendations with limited level of evidence, possibly leading to diverse OAC management and different outcomes. Therefore, we aimed to evaluate real-world implementation and outcome of three guidelines on OAC management in ACHD patients with AA. METHODS: The ESC GUCH 2010, PACES/HRS 2014 and ESC atrial fibrillation (AF) 2016 guidelines were assessed for implementation. ACHD patients with recurrent or sustained non-valvular AA from 5 tertiary centers were identified using a national ACHD registry. After two years of prospective follow-up, thromboembolism, major bleeding and death were assessed. RESULTS: In total, 225 adults (mean age 54±15years, 55% male) with various defects (simple 43%; moderate 37%; complex 20%) and AA were included. Following the most strict indication (OAC is recommended in all three guidelines), one should treat a mere 37% of ACHD patients with AA, whereas following the least strict indication (OAC is recommended in any one of the three guidelines), one should treat 98% of patients. The various guidelines were implemented in 54-80% of patients. From all recommendations, Fontan circulation, CHA2DS2-VASc≥1 and AF were independently associated with OAC prescription. Superiority of any guideline in identifying outcome (n=15) could not be demonstrated. CONCLUSIONS: The implementation of current guidelines on OAC management in ACHD patients with AA is low, probably due to substantial heterogeneity among guidelines. OAC prescription in daily practice was most consistent in patients with AF and CHA2DS2-VASc≥1 or Fontan circulation.

SMAD4 gene mutation increases the risk of aortic dilation in patients with hereditary haemorrhagic telangiectasia.

BACKGROUND: Mutations in the genes ENG, ACVRL1 and SMAD4 that are part of the transforming growth factor-beta signalling pathway cause hereditary haemorrhagic telangiectasia (HHT). Mutations in non-HHT genes within this same pathway have been found to associate with aortic dilation. Therefore, we investigated the presence of aortic dilation in a large cohort of HHT patients as compared to non-HHT controls. METHODS: Chest computed tomography of consecutive HHT patients (ENG, ACVRL1 and SMAD4 mutation carriers) and non-HHT controls were reviewed. Aortic root dilation was defined as a z-score>1.96. Ascending and descending aorta dimensions were corrected for age, gender and body surface area. RESULTS: In total 178 subjects (57.3% female, mean age 43.9±14.9years) were included (32 SMAD4, 47 ENG, 50 ACVRL1 mutation carriers and 49 non-HHT controls). Aortopathy was present in a total of 42 subjects (24% of total). Aortic root dilatation was found in 31% of SMAD4, 2% of ENG, 6% of ACVRL1 mutation carriers, and 4% in non-HHT controls (p<0.001). The aortic root diameter was 36.3±5.2mm in SMAD4 versus 32.7±3.9mm in the non-SMAD4 group (p=0.001). SMAD4 was an independent predictor for increased aortic root (ß-coefficient 3.5, p<0.001) and ascending aorta diameter (ß-coefficient 1.6, p=0.04). CONCLUSIONS: SMAD4 gene mutation in HHT patients is independently associated with a higher risk of aortic root and ascending aortic dilation as compared to other HHT patients and non-HHT controls.

Impact of atrial arrhythmias on outcome in adults with congenital heart disease.

BACKGROUND: Adults with congenital heart disease (ACHD) are affected by atrial arrhythmias (AA). To elucidate the impact of AA on prognosis, we aimed to determine the impact of AA on death, heart failure and stroke in ACHD patients in a prospective nationwide clinical registry. METHODS: All patients aged ≥18years included in the CONCOR registry per October 1st 2015 were analysed. Prior AA was defined as atrial fibrillation, atrial flutter or unspecified AA before inclusion in CONCOR and new-onset AA as a first documented AA during follow-up. The outcomes were death, first stroke and first admission for heart failure (HF). RESULTS: The study cohort comprised 14,224 patients (baseline median age 33.6 [IQR 23-47], male 49.5%, AA n=1501, complex defect 10.3%, repaired defect 58.9%). Median follow-up was 6.5years [IQR 3-10]. Adjusting for age, sex, repair status and defect severity, patients with prior AA had higher mortality and more HF admissions, but no increased risk of stroke compared to those without AA (HR=2.11; 95% CI=1.79-2.49; p<0.001, HR=4.06; 95% CI=2.66-6.19; p<0.001 and HR=1.09; 95% CI=0.71-1.68; p=0.698, respectively). New-onset AA during follow-up was significantly associated with stroke (HR=2.04; 95% CI=1.05-3.96; p=0.036). CONCLUSIONS: ACHD patients with prior AA have a 2-fold increased risk of death and a 4-fold increased risk of heart failure, but no increased risk for stroke compared to those without AA. Defect severity and age appear to be more important risk factors for stroke than prior AA. Stroke risk is increased only after conversion of new onset AA.

Clinical course of tricuspid regurgitation in repaired tetralogy of Fallot.

BACKGROUND: Little is known on the clinical course of tricuspid regurgitation (TR) in patients with repaired tetralogy of Fallot (rTOF) and which patients are at particular risk. This study aims to determine TR course, characteristics associated with TR progression, and the prognostic relevance of TR in rTOF patients. METHODS: In this dualcenter cohort study, rTOF patients from a prospective national registry with ≥1 cardiac magnetic resonance imaging study and ≥2 echocardiograms available were included. Clinical and imaging data were collected. Cox hazards regression analysis was used to assess patient characteristics associated with progression to severe TR and whether severe TR was associated with the combined clinical endpoint of tachyarrhythmia, heart failure, and death, as time-dependent factor. RESULTS: A total of 216 patients were included (57% men, age 34±12years); 11 patients (5%) had severe TR at baseline. During 7.6±3.5years of follow-up, progression to severe TR occurred in 15 patients (7%). NYHA class ≥2 (HR 5.38, 95%-C.I. 1.91-15.16, p=0.001) and moderate baseline TR (HR 13.10, 95%-C.I. 2.95-58.21, p=0.001) were independently associated with progression to severe TR. Adverse events occurred in 47 patients (22%). The occurrence of severe TR was independently associated with adverse events (HR 3.48, 95%-C.I. 1.68-7.21, p=0.001). CONCLUSIONS: In this study, severe TR was present in 12% of adult rTOF patients during 7.6years, and progression to severe TR was most likely in symptomatic patients with moderate baseline TR. In these patients, close surveillance is warranted, because the occurrence of severe TR was associated with worse prognosis.

Mortality in pulmonary arterial hypertension due to congenital heart disease: Serial changes improve prognostication.

BACKGROUND: Adult patients with pulmonary arterial hypertension due to congenital heart disease (PAH-CHD) suffer from high mortality. This underlines the importance of adequate risk stratification to guide treatment decisions. Several baseline parameters are associated with mortality, however, their prognostic value may weaken after years of follow-up. Therefore we investigated the prognostic value of serial changes in standard clinical parameters in PAH-CHD. METHODS: In this prospective observational cohort study we included consecutive PAH-CHD adults, between 2005 and 2016. Control visits to the outpatient clinic were standardized, including functional, biochemical and echocardiographic tests, according to the guidelines. The prognostic value of serial changes was determined with time-dependent Cox regression. RESULTS: Ninety-two patients with PAH-CHD were included (age 43±15years, 34% male, 38% Down, 73% Eisenmenger). During a median follow-up of 6.0 (IQR 3.7-9.3) years, 35 (38%) patients died. Serial changes in World Health Organization functional classification (WHO-FC, HR 18.34 for onset class IV), six-minute walk distance (6-MWD, HR 0.65 per 50m), oxygen saturation at peak exercise (peak SaO2, HR 0.74 per 5%), NTproBNP (HR 2.25 per 1000ng/l) and echocardiographic right ventricular function (TAPSE, HR 0.80 per 0.5cm) significantly predicted mortality. Moreover, serial changes in these parameters were more potent predictors compared to baseline parameters, based on reduction in -2 log likelihood. CONCLUSIONS: Serial changes in standard clinical parameters have more prognostic value compared to baseline parameters in PAH-CHD. Our results emphasize the importance of screening for serial changes since periodical assessment could guide treatment decisions to delay disease progression.

Uteroplacental Doppler flow and pregnancy outcome in women with tetralogy of Fallot.

OBJECTIVE: Pregnancy in women with surgically corrected tetralogy of Fallot (ToF) is associated with cardiac, obstetric and neonatal complications. We compared uteroplacental Doppler flow (UDF) measurements and pregnancy outcome in women with ToF and in healthy women and aimed to assess whether a relationship exists between cardiac function and UDF in women with ToF. METHODS: We evaluated prospectively pregnant women with ToF and healthy pregnant women from the ZAHARA studies. Clinical evaluation, standardized echocardiography and UDF measurements were performed at 20 and 32 weeks' gestation. RESULTS: We included 62 women with ToF and 69 healthy controls. Cardiac complications, mostly arrhythmia, occurred in 8.1% of women with ToF. There was a higher incidence of small-for-gestational age (21.0% vs 4.4%, P = 0.004) and low birth weight (16.1% vs 2.9%, P = 0.009) in the group of women with ToF than in healthy controls. In women with ToF, early diastolic notching of uterine artery waveform at 20 and 32 weeks occurred more frequently (9.8% vs 1.5%, P = 0.034 and 7.0% vs 0%, P = 0.025, respectively) and the umbilical artery pulsatility index at 32 weeks was higher (1.02 ± 0.20 vs 0.94 ± 0.17, P = 0.015) than in healthy controls. Right ventricular function parameters prepregnancy and at 20 weeks' gestation were significantly associated with abnormal UDF. UDF parameters were associated with adverse neonatal outcome. CONCLUSION: The majority of women with surgically corrected ToF tolerate pregnancy well. However, UDF indices are more frequently abnormal in these women, suggesting impaired placentation. The association of impaired right ventricular function parameters with abnormal UDF suggests that cardiac dysfunction contributes to defective placentation or placental perfusion mismatch and may explain the increased incidence of obstetric and neonatal complications. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

The effect of losartan therapy on ventricular function in Marfan patients with haploinsufficient or dominant negative FBN1 mutations.

BACKGROUND: Mild biventricular dysfunction is often present in patients with Marfan syndrome. Losartan has been shown to reduce aortic dilatation in patients with Marfan syndrome. This study assesses the effect of losartan on ventricular volume and function in genetically classified subgroups of asymptomatic Marfan patients without significant valvular regurgitation. METHODS: In this predefined substudy of the COMPARE study, Marfan patients were classified based on the effect of their FBN1 mutation on fibrillin-1 protein, categorised as haploinsufficient or dominant negative. Patients were randomised to a daily dose of losartan 100 mg or no additional treatment. Ventricular volumes and function were measured by magnetic resonance imaging at baseline and after 3 years of follow-up. RESULTS: Changes in biventricular dimensions were assessed in 163 Marfan patients (48 % female; mean age 38 ± 13 years). In patients with a haploinsufficient FBN1 mutation (n = 43), losartan therapy (n = 19) increased both biventricular end diastolic volume (EDV) and stroke volume (SV) when compared with no additional losartan (n = 24): left ventricular EDV: 9 ± 26 ml vs. -8 ± 24 ml, p = 0.035 and right ventricular EDV 12 ± 23 ml vs. -18 ± 24 ml; p < 0.001 and for left ventricle SV: 6 ± 16 ml vs. -8 ± 17 ml; p = 0.009 and right ventricle SV: 8 ± 16 ml vs. -7 ± 19 ml; p = 0.009, respectively. No effect was observed in patients with a dominant negative FBN1 mutation (n = 92), or without an FBN1 mutation (n = 28). CONCLUSION: Losartan therapy in haploinsufficient Marfan patients increases biventricular end diastolic volume and stroke volume, furthermore, losartan also appears to ameliorate biventricular filling properties.

Transition from paediatric to adult care of adolescent patients with congenital heart disease: a pathway to optimal care.

INTRODUCTION: Adolescents with congenital heart disease transition from a paediatric to an adult setting. This is associated with loss-to-follow-up and suboptimal care. Increasing numbers of patients justify a special program. In this study we evaluated the cooperative program between paediatric and adult cardiology departments in a tertiary referral centre. METHODS: In this retrospective study, patients with congenital heart disease with at least one appointment scheduled at the transition program between January 2010 and January 2015 were included. They were seen by a paediatric cardiologist at the age of 15 years in the paediatric department and from age 18 to 25 in the adult department. Demographic and medical data were collected from the electronic patient files. RESULTS: A total of 193 patients (105 males, 88 females) were identified. Sex distribution was almost equal. Most patients were 18-21 years of age. The largest group, 128 patients (67 %), lived within 50 kilometres of our hospital. Paediatric cardiologists referred 157 (81 %) of patients. General practitioners and cardiologists from outside our centre were important referrers for patients lost to follow-up, together accounting for 9 %. A total of 34 (18 %) patients missed an appointment without notification. Repeat offenders, 16 of 34 patients, formed a significant minority within this group. A total of 114 (59 %) patients were attending school, 46 (24 %) were employed, and 33 (17 %) patients were inactive. Activities are in line with capabilities. A nurse practitioner was involved with the 7 % with complex and psychosocial problems. Moderately severe congenital heart defects formed the largest patient category of 102 (53 %) patients. In 3 % of patients the diagnosis had to be revised or was significantly incomplete. In 30 (16 %) patients, cardiac diagnosis was part of a syndrome. Of the 193 patients, 117 (92 %) were in NYHA class I, with 12 (6 %) and 4 (2 %) patients falling into classes II and III, respectively. CONCLUSIONS: A viable transition program can be built by collaboration between paediatric and adult cardiology departments with the same treating physician taking care of patients between 15 and 25 years of age. General practitioners are important in returning lost-to-follow-up patients to specialised care. Nurse practitioners are essential in the care for patients with complex congenital heart disease.

Mobile health in adults with congenital heart disease: current use and future needs.

OBJECTIVE: Many adults with congenital heart disease (CHD) are affected lifelong by cardiac events, particularly arrhythmias and heart failure. Despite the care provided, the cardiac event rate remains high. Mobile health (mHealth) brings opportunities to enhance daily monitoring and hence timely response in an attempt to improve outcome. However, it is not known if adults with CHD are currently using mHealth and what type of mHealth they may need in the near future. METHODS: Consecutive adult patients with CHD who visited the outpatient clinic at the Academic Medical Center in Amsterdam were asked to fill out questionnaires. Exclusion criteria for this study were mental impairment or inability to read and write Dutch. RESULTS: All 118 patients participated (median age 40 (range 18-78) years, 40 % male, 49 % symptomatic) and 92 % owned a smartphone. Whereas only a small minority (14 %) of patients used mHealth, the large majority (75 %) were willing to start. Most patients wanted to use mHealth in order to receive more information on physical health, and advice on progression of symptoms or signs of deterioration. Analyses on age, gender and complexity of defect showed significantly less current smartphone usage at older age, but no difference in interest or preferences in type of mHealth application for the near future. CONCLUSION: The relatively young adult CHD population only rarely uses mHealth, but the majority are motivated to start using mHealth. New mHealth initiatives are required in these patients with a chronic condition who need lifelong surveillance in order to reveal if a reduction in morbidity and mortality and improvement in quality of life can be achieved.

Relationship between atrial septal defects and asthma-like dyspnoea: the impact of transcatheter closure.

BACKGROUND: Patients with atrial septal defects (ASD) are often misdiagnosed as asthma patients and accordingly receive erroneous bronchodilator treatment. In order to characterise their symptoms of dyspnoea to explain this clinical observation, we investigated the prevalence of asthma-like symptoms in patients with secundum ASD who then underwent successful percutaneous closure. METHODS: A total of 80 ASD patients (74 % female, mean age 46.7 ± 16.8 years, median follow-up 3.0 [2.0-5.0] years) retrospectively completed dyspnoea questionnaires determining the presence and extent of cough, wheezing, chest tightness, effort dyspnoea and bronchodilator use on a 7-point scale (0 = none, 6 = maximum) before and after ASD closure. The Mini Asthma Quality of Life (Mini-AQLQ) and Asthma Control Questionnaire with bronchodilator use (ACQ6) were administered. RESULTS: A total of 48 (60 %) patients reported cough, 27 (34 %) wheezing, 26 (33 %) chest tightness and 62 (78 %) effort dyspnoea. Symptom resolution or reduction was found in 64 (80 %) patients after ASD closure. Asthma symptom scores decreased significantly on the Mini-AQLQ and ACQ6 (both p < 0.001). The number of patients using bronchodilators decreased from 16 (20 %) to 8 (10 %) patients after ASD closure (p = 0.039) with less frequent use of bronchodilators (p = 0.015). CONCLUSIONS: A high prevalence of asthma-like symptoms and bronchodilator use is present in ASD patients, which exceeds the low prevalence of bronchial asthma in this study population. Future prospective research is required to confirm this phenomenon. The presence of an ASD should be considered in the differential diagnosis of patients with asthma-like symptoms, after which significant symptom relief can be achieved by ASD closure.