Cardiac thrombus dissolution in acute ischemic stroke: A substudy of Mind the Heart.

Background: Cardiac thrombi are an important cause of ischemic stroke but are infrequently detected on cardiac imaging. We hypothesized that this might be explained by early dissolution of these cardiac thrombi after stroke occurrence. Methods: We performed a single-center observational pilot study between November 2019 and November 2020, embedded in the larger "Mind-the-Heart" study. We included patients with AIS and a cardiac thrombus in the left atrium or ventricle (filling defect <100 Hounsfield Units) diagnosed on cardiac CT that was acquired during the initial stroke imaging protocol. We repeated cardiac CT within one week to determine if the thrombus had dissolved. Results: Five patients (four men, median age 52 years, three with atrial fibrillation and one with anticoagulation therapy at baseline) were included. Median time from symptom onset to first cardiac CT was 383 (range 42-852) minutes and median time from first to second cardiac CT was three days (range 1-7). Two patients received intravenous thrombolysis (IVT). In total, six thrombi were seen on initial CT imaging (one in the left ventricle, four in the left atrial appendage, one in the left atrium). The left atrium thrombus and one left atrial appendage thrombus had dissolved on follow-up cardiac CT, one of which was in a patient with IVT treatment. Conclusion: This pilot study illustrates that cardiac thrombi can dissolve within days of stroke occurrence both with and without IVT treatment.

Detection of patent foramen ovale in patients with ischemic stroke on prospective ECG-gated cardiac CT compared to transthoracic echocardiography.

BACKGROUND: Cardiac CT acquired during the acute stroke imaging protocol is an emerging alternative to transthoracic echocardiography (TTE) to screen for sources of cardioembolism. Currently, its diagnostic accuracy to detect patent foramen ovale (PFO) is unclear. METHODS: This was a substudy of Mind the Heart, a prospective cohort in which consecutive adult patients with acute ischemic stroke underwent prospective ECG-gated cardiac CT during the initial stroke imaging protocol. Patients also underwent TTE. We included patients < 60 years who underwent TTE with agitated saline contrast (cTTE) and assessed sensitivity, specificity, negative and positive predictive value of cardiac CT for the detection of PFO using cTTE as the reference standard. RESULTS: Of 452 patients in Mind the Heart, 92 were younger than 60 years. Of these, 59 (64%) patients underwent both cardiac CT and cTTE and were included. Median age was 54 (IQR 49-57) years and 41/59 (70%) were male. Cardiac CT detected a PFO in 5/59 (8%) patients, 3 of which were confirmed on cTTE. cTTE detected a PFO in 12/59 (20%) patients. Sensitivity and specificity of cardiac CT were 25% (95% CI 5-57%) and 96% (95% CI 85-99%), respectively. Positive and negative predictive values were 59% (95% CI 14-95) and 84% (95% CI 71-92). CONCLUSION: Prospective ECG-gated cardiac CT acquired during the acute stroke imaging protocol does not appear to be a suitable screening method for PFO due to its low sensitivity. Our data suggest that if cardiac CT is used as a first-line screening method for cardioembolism, additional echocardiography remains indicated in young patients with cryptogenic stroke, in whom PFO detection would have therapeutic consequences. These results need to be confirmed in larger cohorts.

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.

Transcatheter tricuspid valve repair: early experience in the Netherlands.

BACKGROUND: Symptomatic tricuspid regurgitation (TR) is increasingly prevalent and impairs quality of life and survival, despite medical treatment. Transcatheter tricuspid valve repair (TTVR) has recently become available as a treatment option for patients not eligible for tricuspid valve surgery. In this study we describe the early experience with TTVR in the Netherlands. METHODS: All consecutive patients scheduled for TTVR in two tertiary hospitals were included in the current study. Patients were symptomatic and had severe functional TR. TTVR was performed either with the MitraClip (off-label use) or dedicated TriClip delivery system and device. Procedural success was defined as achievement of clip implantation, TR reduction ≥ 1 grade and no need for re-do surgical or transcatheter intervention. Clinical improvement was evaluated after 4 weeks. RESULTS: Twenty-one patients (median age 78 years, 33% male, 95% New York Heart Association class ≥ 3, 100% history of atrial fibrillation) underwent TTVR. Procedural success was achieved in 16 patients, of whom 15 reported symptomatic improvement (New York Heart Association class 1 or 2). There was no in-hospital mortality and no major complications occurred. Baseline glomerular filtration rate and TR coaptation gap size were associated with procedural success. CONCLUSION: The current study showed that TTVR seems a promising treatment option for patients with severe functional TR deemed high risk for surgery. Successful TR reduction is most likely in patients with limited coaptation gap size and strongly determines clinical benefit. Adequate patient selection and timing of treatment seem essential for an optimal patient outcome.

Early N-terminal pro-B-type natriuretic peptide is associated with cardiac complications and function during pregnancy in congenital heart disease.

BACKGROUND: Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at 20 weeks' gestation predict adverse cardiovascular (CV) complications during pregnancy in women with congenital heart disease (CHD). To improve early risk assessment in these women, we investigated the predictive value of first-trimester NT-proBNP for CV complications and its association with ventricular function during pregnancy. METHODS: Pregnant women with CHD, previously enrolled in a prospective national study or evaluated by an identical protocol, were included. Clinical data, echocardiographic evaluation and NT-proBNP measurements were obtained at 12, 20 and 32 weeks' gestation. Elevated NT-proBNP was defined as > 235 pg/ml (95th percentile reference value of healthy pregnant women in the literature). RESULTS: We examined 126 females (mean age 29 years). Elevated NT-proBNP at 12 weeks was associated with CV complications (n = 7, 5.6%, odds ratio 10.9, p = 0.004). Arrhythmias were the most common complication (71%). The negative predictive value of low NT-proBNP to exclude CV complications was 97.2%. In women with CV complications, NT-proBNP levels remained high throughout pregnancy, while a decrease was seen in women without CV complications (p < 0.001 for interaction between group and time). At 12 weeks, higher NT-proBNP levels were associated with impaired subpulmonary ventricular function (p < 0.001) and also with a decline in subpulmonary ventricular function later in pregnancy (p = 0.012). CONCLUSIONS: In this study, first-trimester NT-proBNP levels were associated with adverse CV complications and a decline in subpulmonary ventricular function later in pregnancy in women with CHD. Early NT-proBNP evaluation is useful for tailored care in pregnant women with CHD.

Long-term (>10-year) clinical follow-up after young embolic stroke/TIA of undetermined source.

BACKGROUND: To date, the pathophysiology of first-ever and recurrent stroke/TIA still remains unclear in young patients with embolic stroke/TIA of undetermined source (ESUS). Clinical studies with long-term follow-up in young ESUS patients are necessary to investigate the underlying pathophysiology of first-ever and recurrent stroke/TIA in this patient population, in particular the role of new-onset atrial fibrillation. AIMS: Our aim was to study the long-term (>10-year) clinical outcome of young patients (<50 years) with ESUS. METHODS: This cohort study included all patients aged ≤ 50 years who underwent transoesophageal echocardiography for diagnostic work-up of ESUS during 1996-2008 from one tertiary center. All patients were contacted by telephone between September-November 2018 to update clinical information from medical records. The clinical outcomes of this study were incidence rates of all-cause and cardiovascular mortality, recurrent stroke/TIA, new-onset clinical AF, and ischemic vascular events. RESULTS: In total, 108 patients (57% female, mean age 40 ± 7.2 years [range 19-50 years], n = 72 stroke) were included. Across clinical follow-up (median 13[IQR 10-16] years), 24 patients died (n = 14 cardiovascular). The 15-year incidence rate of recurrent stroke/TIA was 15% (incidence rate = 1.09[95%CI 0.54-1.65]/100 patient-years) and a 5.5% incidence of new-onset clinical AF (incidence rate = 0.44[95%CI 0.09-0.79]/100 patient-years) following ESUS. CONCLUSIONS: The incidence of recurrent stroke/TIA is relatively high during long-term clinical follow-up of young patients with ESUS. In contrast, new-onset clinical AF is relatively low and therefore may not play an important part in the pathophysiology of first-ever and recurrent stroke/TIA of these patients.

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.

Preoperative frailty parameters as predictors for outcomes after transcatheter aortic valve implantation: a systematic review and meta-analysis.

Guidelines suggest using frailty characteristics in the work-up for a transcatheter aortic valve implantation (TAVI). There are many frailty-screening tools with different components. The prognostic value of the individual parameters in frailty is as yet unclear. The objective of this systematic review and meta-analysis was to find and pool predictors for 1­year mortality after TAVI. We followed a two-step approach. First, we searched for randomised controlled trials on TAVI to identify frailty parameters used in these studies. Second, we searched for publications on these frailty parameters. Articles were included for pooled analysis if the studied frailty parameters were dichotomised with clear cut-off values based on common standards or clinical practice and reported adjusted hazard ratios (HR) of 1­year mortality after TAVI. We calculated pooled effect estimates of 49 studies based on dichotomised frailty scores (HR: 2.16, 95% CI: 1.57-3.00), chronic lung disease (HR: 1.57, 95% CI: 1.45-1.70), estimated glomerular filtration rate <30 ml/min (HR: 1.95, 95% CI: 1.68-2.29), body mass index <20 kg/m2 (HR: 1.49, 95% CI: 1.09-2.03), hypoalbuminaemia (HR: 1.77, 95% CI: 1.38-2.25), anaemia (HR: 2.08, 95% CI: 0.93-4.66), low gait speed (HR: 13.33, 95% CI: 1.75-101.49) and Katz activities of daily living (ADL) score of 1 or more deficits (HR: 5.16, 95% CI: 0.77-34.47). Chronic lung disease, chronic kidney disease, underweight, hypoalbuminaemia, a low frailty score, anaemia, low gait speed and an ADL deficiency were associated with worse 1­year outcomes after TAVI.

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.

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.

Can stress echocardiography identify patients who will benefit from percutaneous mitral valve repair?

The aim of the current study was to investigate whether stress echocardiography improves selection of patients who might have clinical benefit from percutaneous mitral valve repair with the MitraClip. In total, 39 patients selected for MitraClip implantation underwent preprocedural low-dose stress (dobutamine or handgrip) echocardiography from which stroke volume, ejection fraction and MR grade were measured. Outcome after MitraClip implantation was determined by New York Heart Association classification and Quality of Life questionnaires. Clinical benefit from MitraClip treatment was defined as survival and NYHA class I-II at 6 months follow-up. In total, 36 patients with a technically successful procedure were included in the analysis (mean age 79 ± 8 years, 47% male, 50% functional MR). Clinical benefit was achieved in 18 patients. All seven patients with MR decreasing during stress remained in NYHA III-IV or died within 6 months, while 62% (18 out of 29) of the patients with stable or increased MR during stress had clinical benefit (p = 0.008). Significant increase in Quality of Life on 4/8 subscales of the RAND Short Form-36 questionnaire was observed: Physical Functioning (p < 0.001), Social Functioning (p < 0.001), Mental Health (p = 0.022) and Vitality (p = 0.026) was seen in patients with an increase in stroke volume during stress echocardiography. Patients with a decreased MR during preprocedural stress echocardiography remained more symptomatic than patients with a stable or increased MR during stress. Stress echocardiography may support patient selection for percutaneous mitral valve repair.

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.

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.