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.

Perceived health is partially associated with the symptomatological profile in patients with benign and severe conditions: the case of congenital heart disease.

PURPOSE: Individuals with serious medical conditions can perceive their health status as good. This might be explained by the symptomatology inherent to the condition. Research in this respect is scarce. Congenital heart disease (CHD) is a spectrum of mild, moderate, and complex heart defects, representing more benign and severe chronic conditions. We investigated (1) symptomatology (i.e., symptom frequency and symptom distress) of CHD patients; (2) the extent to which symptomatology was independently related to perceived health; and (3) the relative importance of individual symptoms for perceived health. METHODS: A secondary data analysis on two separate patient samples (629 Belgian and 1,109 Dutch patients) was conducted. Patients' symptomatology was measured with the TAAQOL-CHD. Perceived health was measured by the EQ-5Dvas in Belgian patients, and by a single item (EVGFP rating) of the SF-36 in Dutch patients. Linear regression analyses were performed to investigate the relationship between symptoms and perceived health, while controlling for sex, age, disease complexity, and functional status. RESULTS: The most frequently occurring symptoms were dizziness, palpitations, and nycturia. Symptom distress was associated with perceived health, independent of confounders. Symptom distress with respect to shortness of breath while walking; palpitations; and dizziness were independently related to perceived health. CONCLUSIONS: Perceived health in CHD patients is partially associated with their symptomatology. This finding underscores the possibility that differences in perceived health across patient groups with more benign and severe conditions may be caused by the different impact conditions have--in terms of symptoms--on the day-to-day life.

Infective endocarditis in patients after percutaneous pulmonary valve implantation with the stent-mounted bovine jugular vein valve: Clinical experience and evaluation of the modified Duke criteria.

AIMS: Percutaneous pulmonary valve implantation (PPVI) has proven good hemodynamic results. As infective endocarditis (IE) remains a potential complication with limited available clinical data, we reviewed our patient records to improve future strategies of IE prevention, diagnosis and treatment. METHODS: Medical records of all patients diagnosed with Melody® valve IE according to the modified Duke criteria were retrospectively analyzed in three Belgian tertiary centers. RESULTS: 23 IE episodes in 22 out of 240 patients were identified (incidence 2.4% / patient year) with a clear male predominance (86%). Median age at IE was 17.9 years (range 8.2-45.9 years) and median time from PPVI to IE was 2.4 years (range 0.7-8 years). Streptococcal species caused 10 infections (43%), followed by Staphylococcus aureus (n = 5, 22%). In 13/23 IE episodes a possible entry-point was identified (57%). IE was classified as definite in 15 (65%) and as possible in 8 (35%) cases due to limitations of imaging. Echocardiography visualized vegetations in only 10 patients. PET-CT showed positive FDG signals in 5/7 patients (71%) and intracardiac echocardiography a vegetation in 1/1 patient (100%). Eleven cases (48%) had a hemodynamically relevant pulmonary stenosis at IE presentation. Nine early and 6 late percutaneous or surgical re-interventions were performed. No IE related deaths occurred. CONCLUSIONS: IE after Melody® valve PPVI is associated with a relevant need of re-interventions. Communication to patients and physicians about risk factors is essential in prevention. The modified Duke criteria underperformed in diagnosing definite IE, but inclusion of new imaging modalities might improve diagnostic performance.

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.

Transapical left ventricular access for difficult to reach interventional targets in the left heart.

OBJECTIVE: Interventional targets may be virtually "excluded" due to vascular access problems or complex previous surgical procedures. This study reviews our experience using transapical ventricular puncture to gain direct access to the systemic ventricle. PATIENTS: Patient 1 (74 years, 2 previous sternotomies), patient 2 (66 years, 5 previous sternotomies), and patient 5 (69 years, 3 previous sternotomies) with prosthetic valves had paravalvular mitral valve leaks. Patient 3 (6.3 years, 2 previous sternotomies) with an extracardiac Fontan conduit, had a significant residual leak after two previous surgical attempts of patch closure of a severely regurgitant right atrioventricular valve. Patient 4 (10 months) had failure of standard ablation of the posteroseptal region of the mitral valve with persistent life-threatening episodes of ventricular tachycardia. METHODS: Procedures were performed under general anesthesia. Entry site was percutaneous in three patients and in two (and one conversion) a mini-thoracotomy was used. Sheaths were placed (6 F) using standard Seldinger technique, followed by the procedure as required. Direct surgical closure of the puncture site was done in 4 patients and in patient 3, a percutaneous vascular occlusion device was used. RESULTS: Easy and immediate access was obtained in all patients. The paravalvular leaks were crossed within seconds and completely closed with Amplatzer occluders. In patient 3 the valve was crossed using a Brokenbrough needle and a 12-mm Amplatzer device was placed in the patch leak. Patient 4 was successfully ablated using a 7-F irrigated catheter endo- and epicardially. Complications were in the percutaneous puncture group: in one patient a coronary artery was punctured and in one a hemothorax developed. CONCLUSION: Direct left ventricular puncture offers a very useful alternative access site in selected patients to reach "inaccessible" targets for certain percutaneous interventions in patients where standard approaches may be impossible or difficult.

Aerosol gene transfer with inducible nitric oxide synthase reduces hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats.

BACKGROUND: Nitric oxide (NO) is a potent vasodilator with an important role in the regulation of pulmonary vascular tone. The effects of NO synthase (NOS) gene transfer on pulmonary vascular remodeling associated with hypoxic pulmonary hypertension are unknown. METHODS AND RESULTS: We aerosolized 3 x 10(9) pfu of an adenoviral vector containing inducible NOS gene (AdNOS2), constitutive NOS3 gene (AdNOS3), or no transgene (AdRR5) into rat lungs. Exhaled NO levels, monitored with chemiluminescence, were higher in AdNOS2-infected rats than in AdNOS3- and AdRR5-infected rats (at 3 days, 33+/-6 ppb, n=9, versus 17+/-4, n=9, and 6+/-2 ppb, n=3, P:<0.05 for both). Exposure to FIO(2) 0.10 for 7 days increased pulmonary artery pressure from 19+/-4 mm Hg (baseline) to 27+/-1 and 26+/-2 mm Hg in AdNOS3- and AdRR5-infected rats, respectively, but only to 21+/-1 mm Hg in AdNOS2-infected animals (P:<0.05). After 7 days of hypoxia, total pulmonary resistance in AdRR5- and AdNOS3-infected rats was significantly higher than in AdNOS2-infected animals (0.41+/-0.05 and 0.39+/-0.07 versus 0.35+/-0. 03 mm Hg. mL(-)(1). min(-)(1), respectively, P:<0.05). Right ventricular hypertrophy was reduced in AdNOS2-infected rats [right ventricular/(left ventricular+septal) weight, 0.19+/-0.10 versus 0. 28+/-0.10 and 0.32+/-0.10 in AdRR5- and AdNOS3-infected rats, respectively, P:<0.05]. The percentage of muscularized precapillary pulmonary resistance vessels was also significantly decreased (18+/-4% versus 25+/-8% and 30+/-5% in AdRR5- and AdNOS3-infected rats, P:<0.05). CONCLUSIONS: Aerosol NOS2 gene transfer increases pulmonary NO production and significantly reduces hypoxic pulmonary hypertension and pulmonary vascular remodeling. Aerosol NOS2 gene transfer may be a promising strategy to target pulmonary vascular disorders.

Changes in QRS duration are associated with maximal exercise capacity in adult patients with repaired tetralogy of Fallot.

OBJECTIVE: In adult patients with repaired tetralogy of Fallot (TF) QRS duration at rest seems to be a predictor of maximal exercise. We examined the relationship between QRS duration during exercise and exercise performance. DESIGN: In 57 consecutive TF patients QRS duration in V1 (ms) was measured at rest, at maximal exercise (Wmax, W), and at peak oxygen consumption (peak VO2, ml/min). Stroke volume (SV) was calculated from cardiac output, obtained by CO2 rebreathing. Spearman rank correlation was used to describe the relationship between QRS duration and exercise performance. Statistical significance was defined as P<0.05. RESULTS: Seven patients, who didn't pass the anaerobic threshold, and one outlier (Wmax=340 W) were excluded, resulting in a sample of 49 patients (75.5% male; median age=24 years, range 16-43 years). QRS duration at rest (median=160 ms, range 78-194 ms) and at maximal exercise (median=153 ms, range 80-193 ms) did not differ significantly. The median change of QRS duration during exercise was -5 ms (range -31 to +83 ms). This was negatively correlated with Peak VO2 (2081+/-577 ml/min; rho=-0.33, P=0.02) and Wmax (182+/-53 Watt; rho=-0.33, P=0.02). In patients with QRS shortening peak VO2 and the exercise induced increase in SV were significantly higher than in patients with QRS shortening. CONCLUSIONS: This study indicates that QRS shortening during exercise in TF patients is related with a better exercise performance. Lower increase in stroke volumes may be responsible for this difference. Further research is needed to elaborate these findings.

Pulmonary stenosis caused by extrinsic compression of an aortic pseudoaneurysm of a composite aortic graft.

Pulmonic stenosis and stenosis of the right ventricular outflow tract related to extrinsic compression have been described in patients with tumors, in a patient with a pericardial cyst, and in patients with vascular abnormalities as an unruptured sinus of Valsalva aneurysm, a giant coronary artery pseudoaneurysm and an aortic arch aneurysm. Composite graft replacement of the ascending aorta and aortic valve with reimplantation of the coronary arteries has some inherent complications. Our case report describes a patient with a pericomposite graft aneurysm presenting as a stenosis of the pulmonary artery, detected by Doppler echocardiography.

Graft dilation after redo surgery for aneurysm formation following patch angioplasty for aortic coarctation.

OBJECTIVES: Aneurysm formation after patch angioplasty for aortic coarctation is a frequent and potentially lethal complication, necessitating surgical reintervention. Although several mechanisms have been postulated, flow disturbance in a concomitant hypoplastic transverse aortic arch most likely contributes to the aneurysm formation. The outcome of the grafts after redo surgery, however, is unknown. The purpose of this study was to evaluate the outcome of the inserted graft in patients with surgery for aneurysm formation following patch angioplasty for coarctation of the aorta. METHODS: In 16 patients redo surgery was performed for aneurysm formation (diameter: 47.1+/-11.9 cm) (mean+/-SD), 12.7+/-2.1 years after the initial patch angioplasty. All patients had a concomitant arch hypoplasia. They were treated by insertion of a Dacron Gelseal graft (16-30 mm), but the associated hypoplastic arch segment was left untouched. To evaluate the evolution of the new graft, patients were followed by means of magnetic resonance (MR) imaging. RESULTS: The immediate postoperative outcome was uneventful in 12 patients. Four patients, however, suffered from a recurrent nerve paralysis and one of them of a spinal cord transection. The mean follow-up time was 54.1+/-17.9 months during which 59 magnetic resonance studies were performed. The number of MR studies per patient ranged from two to seven. The graft diameter increased significantly with 56+/-18%, range 20-82 (P<0.0001). This widening was most pronounced within the first year after surgery (43+/-16%, range 5-67) (P<0.0001). CONCLUSIONS: Flow acceleration caused by an even mild hypoplastic transverse arch can put excessive strain on the distal part of the aortic arch. This can lead not only to aneurysm formation after patch angioplasty but also to excessive dilation of the Dacron Gelseal graft. At intermediate long-term follow-up, however, a stabilization of the graft dilation is observed.

Failure of medicine: evolution of an atrial septal defect to an Eisenmenger syndrome.

The atrial septal defect (ASD) is the most commonly diagnosed congenital defect in adults and has a prevalence of 7.5% of all congenital cardiac anomalies. Less invasive imaging techniques, especially transthoracic and transoesophageal echocardiography, provide more accurate diagnostics, resulting in earlier diagnosis and treatment. Despite these opportunities in high-tech countries, medicine may still fail in detecting initially correctable cardiac anomalies. We present a case of 41-year-old woman with an abnormal murmur at childhood that disappeared with time due to the development of an Eisenmenger syndrome. The importance of a complete haemodynamic evaluation in this patient is illustrated.

Primary balloon dilatation in coarctation of the aorta complicated by severe aortic insufficiency.

The combination of coarctation of the aorta in the presence of severe aortic insufficiency poses a serious clinical problem. Although successful single- and two-stage repair for combined coarctation in the presence of severe aortic regurgitation has been described, the surgical management of this lesion remains particularly difficult. The analysis of larger series of patients operated upon for coarctation reveals significant early mortality rate in patients with associated severe aortic insufficiency. Although the exact cause of the acute left ventricular failure remains unclear and is a matter of debate, one can assume that changes in the haemodynamics, resulting in global myocardial ischaemia from impaired coronary blood supply or a massive volume overload of the left ventricle after the correction of the coarctation, could have led to myocardial irritability and left ventricular failure. We present a three-stage repair with subtotal relief of the coarctation by balloon angioplasty and stenting first; elective aortic valve replacement in a second stage and finally total balloon dilatation of the residual stenosis at the previously subtotal dilated coarcted segment.

Continuous spinal analgesia for labor pain in a parturient with aortic stenosis.

Aortic stenosis in pregnancy carries a high fetal and maternal morbidity and mortality. Spinal analgesia/anesthesia is considered by many to be contraindicated in these patients. The rapid onset of sympathetic block induces hypotension, which can result in myocardial hypoperfusion and myocardial ischemia. We describe a case of moderate to severe aortic stenosis, diagnosed during pregnancy, in which pain relief during labor and delivery was managed using a continuous spinal catheter. Pure intrathecal opioid analgesia was used initially to maintain hemodynamic stability. However after two bolus administrations of sufentanil, analgesia was further maintained using ropivacaine and sufentanil. A spinal catheter was chosen to provide reliable anesthesia, which could be extended rapidly for cesarean section.

Long-term outcome after treatment of isolated pulmonary valve stenosis.

BACKGROUND: Few data are available on very long-term follow-up after treatment for isolated pulmonary valve stenosis (PVS), either surgically or by percutaneous balloon angioplasty (PBA). METHODS AND RESULTS: All patients with isolated PVS were selected from our database of congenital heart defects. Their records were reviewed systematically. We identified 79 surgically treated patients with a median follow-up of 22.5 years (range 0-45 years) and 139 PBA patients with median follow-up of 6.0 years (range 0-21 years). Echocardiographic and catheterization parameters indicate excellent results of both techniques in relieving the transpulmonary gradient. However, after initial surgery 20.3% of patients needed a cardiac re-intervention: 81% for severe pulmonary valve regurgitation, but none for residual pulmonary stenosis. After initial PBA a cardiac re-intervention was needed in 9.4% of patients. In 85% the indication was residual pulmonary stenosis, in none of them pulmonary regurgitation, although almost all patients developed a mild pulmonary regurgitation. Freedom of re-intervention after surgery was 98.4%, 93.5%, 87.7%, 70.9% and 55.7% at 5, 10, 20, 30 and 40 years postoperatively. Freedom of re-intervention in the PBA group was 95.1%, 87.5% and 84.4% at 5, 10 and 20 years post-procedure. CONCLUSIONS: Both surgery and PBA are safe and successful in relieving the acute transpulmonary gradient. Long-term results of surgery are worse than previously thought due to severe PR. After PBA re-interventions for residual stenosis are frequently needed and the incidence of mild PR is high. Very long-term results of PBA are still unknown.

Left atrial myxoma. Evaluation with transoesophageal echocardiographic and real time three-dimensional imaging.

Myxoma is the most common benign cardiac neoplasm. A 66-year-old woman presented with a large left atrial myxoma, which was detected by a real-time three-dimensional echocardiography (RT3DE) and a real-time three-dimensional transoesophageal echocardiography (RT3D-TEE) approach. RT3DE and RT3D-TEE proved to be techniques that can provide additional contributions to the diagnostic investigation of structural heart diseases.

Failure of epicardial pacing leads in congenital heart disease: not uncommon and difficult to predict.

AIMS: We evaluate the incidence of epicardial lead failure and try to identify risk factors in patients with congenital heart disease. METHODS: All patients with a congenital heart defect and an epicardial pacing system, implanted within a timeframe of 25 years, were included in this study. Patients' medical records and lead data were reviewed. Lead failure was defined as the primary endpoint. RESULTS: In total 198 active epicardial leads (atrial 40, ventricular 158) were implanted in 93 patients (median age at implantation 4.4 years (range 0-58.6)). During a total follow-up of 1235 lead-years, 29 lead failures (14.6%, 4 atrial, 25 ventricular) were documented in 22 patients (23.7%). Lead failure occurred at a median time period of 4.8 years (range 1.2-24.1) after implantation. Five-year freedom of lead failure was 88%. The only independent predictor for lead failure was the age at implantation (HR 0.44; 95%CI 0.20-0.97, p = 0.04), other characteristics failed to predict lead failure. Sudden cardiac death occurred in four patients (4.3%), in one a lead failure was documented. CONCLUSION: A high incidence of epicardial lead failures is found in patients with congenital heart disease. Unfortunately, it is difficult to predict this potentially life-threatening complication.

New-onset and persistent migraine early after percutaneous atrial septal defect closure disappear at follow-up.

AIMS: Recently we reported that percutaneous atrial septal defect (ASD) closure had no influence on the prevalence of migraine during a short followup period. 12 % of patients however developed a new-onset migraine after the ASD closure. As it has been suggested that the closing device might induce or maintain migraine temporarily, we were interested in the prevalence of migraine at longer follow-up. METHODS: All 75 patients included in the previous study, received the same structured headache questionnaire. A neurologist, blinded to previous data, diagnosed migraine with or without aura (MA+ or MA-) according to the International Headache Criteria. McNemar paired X2 test was used to evaluate changes in the occurrence of migraine. RESULTS: Seventy-one patients (94.7%) answer the questionnaire (55 women, mean age at closure 51 +/- 18 years). Mean follow-up time was 52 +/- 13 months. The overall migraine prevalence decreased from 30.7% before to 22.5% after closure (P=0.21). A significant reduction was noted in patients with new-onset migraine early after closure (n=7), where migraine disappeared in 6 patients (P=0.031). In the group with persistent migraine early after closure (n=13), another 6 patients became migraine-free (P=0.031). CONCLUSION: Percutaneous ASD closure was not related to a significant decrease in overall migraine prevalence. However, new-onset and persistent migraine early after closure disappeared.

Patent foramen ovale and migraine.

Migraine is a common neurological disorder with a great impact on the quality of life and social activities. The patent foramen ovale (PFO) is an intra-atrial right-to-left shunt with a prevalence of 25% in the general population. An increased prevalence is found in patients with migraine, especially in migraine with aura. Percutaneous PFO closure might decrease the prevalence of migraine. However, most of these observational studies were retrospective without a randomized design and the results need to be interpreted with caution. In this review we describe the association between PFO and migraine and the different pathophysiological hypotheses, which have been proposed to explain this relationship.

Stenting of hypoplastic aortic segments with mild pressure gradients and arterial hypertension.

OBJECTIVE: To determine the safety, feasibility and effectiveness of stent expansion of hypoplastic aortic segments with pressure gradients in patients with arterial hypertension. DESIGN: Non-randomised prospective clinical trial. SETTING: Tertiary referral centre, congenital cardiac unit. PATIENT SELECTION: 20 consecutive patients (median age 14.5 years, range 11.6-38.8 years) with arterial hypertension and a hypoplastic segment of the aorta. Seventeen patients had successful previous arch interventions in a coarctation site. INTERVENTIONS: Stent deployment in hypoplastic arch segments. MAIN OUTCOME MEASURES: Gradient across the aortic arch; complications early and during follow up; residual hypertension. RESULTS: 23 stents were deployed: 13 in the cross and 10 in the isthmus. The mean gradient across the aortic arch decreased from 16 (SD 6) (median 17) to 3 (4) (median 1) mm Hg (p < 0.001). In a few patients a mild gradient persisted just distal to the left carotid artery due to residual orificial narrowing or acute angulation. No complications occurred during or after the procedure. During follow up of 2.2 years (range 0.2-4.8 years) arterial hypertension resolved in 10 patients and 10 required residual drug treatment with better control of blood pressures. CONCLUSIONS: Pressure loss due to residual hypoplastic aortic segments can be treated effectively and safely with stent expansion. Some patients remain mildly hypertensive and require additional drug treatment.