The relationship between perceived parenting practices and anxiety in adults with congenital heart disease.

BACKGROUND: Patients with congenital heart disease (CHD) and their parents face challenges throughout their lives that can lead to anxiety lasting into adulthood. We aim to assess the association between perceived parenting practices and anxiety beyond pediatric medical-surgical histories in adults with CHD. METHODS: A cross-sectional study of adults with CHD was conducted at the Montreal Heart Institute (MHI). Perception of parental practices during childhood was retrospectively assessed using validated self-report questionnaires, while anxiety in adulthood was assessed with the Hospital Anxiety and Depression Scale (HADS). Sociodemographic and medical information were collected from a questionnaire and medical records. Hierarchical multiple linear regression was conducted. RESULTS: Of the 223 participants, 59% were female, and the mean age was 46 ± 14 years. Perceived parenting practices explained more variance (11%) in the anxiety score than pediatric medical-surgical history (2%). In our final model, anxiety was significantly associated with age, parental history of anxiety, and positive parenting practices, but not with overprotection. CONCLUSIONS: Parenting practices are associated with anxiety in adults with CHD beyond pediatric medical-surgical history and sociodemographic. Positive parenting practices may be protective against anxiety in adulthood. Longitudinal studies are needed to determine causality.

Pulmonary vascular disease and optical coherence tomography imaging in patients with Fontan palliation.

INTRODUCTION: The Fontan procedure is the palliative procedure of choice for patients with single ventricle physiology. Pulmonary vascular disease (PVD) is an important contributor to Fontan circulatory failure. AREAS COVERED: We review the pathophysiology of PVD in patients with Fontan palliation and share our initial experience with optical coherence tomography (OCT) in supplementing standard hemodynamics in characterizing Fontan-associated PVD. In the absence of a sub-pulmonary ventricle, low pulmonary vascular resistance (PVR; ≤2 WU/m2) is required to sustain optimal pulmonary blood flow. PVD is associated with adverse pulmonary artery (PA) remodeling resulting from the non-pulsatile low-shear low-flow circulation. Predisposing factors to PVD include impaired PA growth, endothelial dysfunction, hypercoagulable state, and increased ventricular end-diastolic pressure. OCT parameters that show promise in characterizing Fontan-associated PVD include the PA intima-to-media ratio and wall area ratio (i.e. difference between the whole-vessel area and the luminal area divided by the whole-vessel area). EXPERT OPINION: OCT carries potential in characterizing PVD in patients with Fontan palliation. PA remodeling is marked by intimal hyperplasia, with medial regression. Further studies are required to determine the role of OCT in informing management decisions and assessing therapeutic responses.

Impact of Fontan Fenestration on Adverse Cardiovascular Outcomes: A Multicentre Study.

BACKGROUND: Fenestrating a Fontan baffle has been associated with improved perioperative outcomes in patients with univentricular hearts. However, longer-term potential adverse effects remain debated. We sought to assess the impact of a fenestrated Fontan baffle on adverse cardiovascular events including all-cause mortality, cardiac transplantation, atrial arrhythmias, and thromboemboli. METHODS: A multicentre North American retrospective cohort study was conducted on patients with total cavopulmonary connection Fontan baffle, with and without fenestration. All components of the composite outcome were independently adjudicated. Potential static and time-varying confounders were taken into consideration, along with competing risks. RESULTS: A total of 407 patients were followed for 10.4 (7.1-14.4) years; 70.0% had fenestration of their Fontan baffle. The fenestration spontaneously closed or was deliberately sealed in 79.9% of patients a median of 2.0 years after Fontan completion. In multivariable analysis in which a persistent fenestration was modelled as a time-dependent variable, an open fenestration did not confer a higher risk of the composite outcome (hazard ratio, 1.18; 95% confidence interval, 0.71-1.97; P = 0.521). In secondary analyses, an open fenestration was not significantly associated with components of the primary outcome: that is, mortality or transplantation, atrial arrhythmias, or thromboemboli. However, sensitivity analyses to assess the possible range of error resulting from imprecise dates for spontaneous fenestration closures could not rule out significant associations between an open fenestration and atrial arrhythmias or thromboemboli. CONCLUSIONS: In this multicentre study, no significant association was identified between an open fenestration in the Fontan baffle and major adverse cardiovascular events.

The Aortic Team Model and Collaborative Decision Pathways for the Management of Complex Aortic Disease: Clinical Practice Update From the Canadian Cardiovascular Society/Canadian Society of Cardiac Surgeons/Canadian Society for Vascular Surgery/Canadian Association for Interventional Radiology.

Disease of the aortic arch, descending thoracic, or thoracoabdominal aorta necessitates dedicated expertise across medical, endovascular, and surgical specialties. Cardiologists, cardiac surgeons, vascular surgeons, interventional radiologists, and others have expertise and skills that aid in the management of patients with complex aortic disease. No specialty is uniformly expert in all aspects of required care. Because of this dispersion of expertise across specialties, an aortic team model approach to decision-making and treatment is advocated. A nonhierarchical partnership across specialties within an interdisciplinary aortic clinic ensures that all treatment options are considered and promotes shared decision-making between the patient and all aortic experts. Furthermore, regionalization of care for aortic disease of increased complexity assures that the breadth of treatment options is available and that favourable volume-outcome ratios for high-risk procedures are maintained. An awareness of best practice care pathways for patient referrals for preventative management, acute care scenarios, chronic care scenarios, and pregnancy might facilitate a more organized management schema for aortic disease across Canada and improve lifelong surveillance initiatives.

Design of the Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor Versus Placebo in Patients With Congenital Systemic Right Ventricle Heart Failure (PARACYS-RV) Trial.

The presence of a systemic right ventricle (sRV) with biventricular physiology (biV) is associated with increased patient morbidity and mortality. To date, no pharmacologic therapy for heart failure has been proven effective for patients with systolic dysfunction of the sRV-biV. We designed a randomized, double-blind, placebo-controlled crossover trial to compare sacubitril/valsartan treatment to placebo in adults (aged ≥ 18 years) with moderate-to-severe sRV-biV dysfunction and New York Heart Association functional class II to III symptoms. Two primary efficacy endpoints are assessed in the trial: exercise capacity (submaximal exercise duration) and neurohormonal activation (N-terminal prohormone brain natriuretic peptide). Secondary objectives include assessing a change in the Kansas City Cardiomyopathy Questionnaire score and evaluating the safety and tolerance of sacubitril/valsartan. A 6-week open run-in phase identifies the maximum tolerated dose of sacubitril/valsartan, up to 97 mg/103 mg twice daily. After a 2-week washout period, patients are randomized 1:1 to sacubitril/valsartan treatment vs placebo for a 24-week phase, followed by another 2-week washout period and subsequent crossover to the alternative treatment arm for an additional 24-week phase. Data to assess primary and secondary endpoints are collected at baseline and at the end of each phase. A total of 48 patients is required to provide > 80% power to detect a 30% difference in distance walked and in N-terminal prohormone brain natriuretic peptide levels with sacubitril/valsartan treatment vs placebo, each with a 2-sided P-value of 0.025. In summary, the Prospective Comparison of Angiotensin Receptor-Neprilysin Inhibitor vs Placebo in Patients With Congenital Systemic Right Ventricular Heart Failure Trial (PARACYS-RV) should determine the role of sacubitril/valsartan in treating heart failure in patients with sRV-biV and carries the potential to alter management of this patient population.

La présence d'un ventricule droit systémique (VDs) avec physiologie biventriculaire (PbiV) est associée à une morbidité et une mortalité accrues chez les patients. À ce jour, aucune pharmacothérapie de l'insuffisance cardiaque ne s'est révélée efficace chez les patients atteints d'une dysfonction systolique du VDs-PbiV. Nous avons conçu un essai croisé, à répartition aléatoire et à double insu, contrôlé par placebo pour comparer la bithérapie sacubitril-valsartan au placebo chez les adultes (≥ 18 ans) ayant une dysfonction modérée ou sévère du VDs-PbiV et des symptômes de la classe fonctionnelle II à III de la New York Heart Association. Deux paramètres d'évaluation principaux de l'efficacité sont définis pour l'essai : tolérance à l'effort (durée d'effort sous-maximal) et activation neurohormonale (propeptide natriurétique de type B N-Terminal [NT-proBNP]). La mesure d'une variation du score au questionnaire sur la cardiomyopathie de Kansas City de même que l'évaluation de l'innocuité et de la tolérance de la bithérapie sacubitril-valsartan sont des objectifs secondaires. Une phase préparatoire de six semaines en mode ouvert permet d'établir la dose maximale tolérée de sacubitril-valsartan, jusqu'à concurrence de 97 mg/103 mg deux fois par jour. Après une période de repos thérapeutique de deux semaines, les patients sont affectés au hasard, dans un rapport 1:1, à la bithérapie sacubitril-valsartan ou au placebo pendant une phase de traitement de 24 semaines, suivie d'une autre période de repos thérapeutique de deux semaines et d'un passage subséquent à l'autre groupe de traitement pendant une phase additionnelle de 24 semaines. Les données sur les paramètres d'évaluation principaux et secondaires sont recueillies au début de l'essai et à la fin de chaque phase. Il faut un total de 48 patients afin d'obtenir une puissance supérieure à 80 % pour détecter une différence de 30 % entre la bithérapie sacubitril-valsartan et le placebo quant à la distance parcourue à la marche et aux taux de NT-proBNP, la valeur p bilatérale étant de 0,025 pour les deux valeurs. En résumé, l'essai PARACYS-RV (Prospective Comparison ofAngiotensinReceptor-Neprilysin Inhibitor vs Placebo in Patients WithCongenital SystemicRightVentricular Heart Failure) doit déterminer le rôle de la bithérapie sacubitril-valsartan dans le traitement de l'insuffisance cardiaque chez les patients ayant un VDs-PbiV et pourrait modifier la prise en charge de cette population de patients.

Feature tracking strain analysis detects the onset of regional diastolic dysfunction in territories with acute myocardial injury induced by transthoracic electrical interventions.

Electric interventions are used to terminate arrhythmia. However, myocardial injury from the electrical intervention can follow unique pathways and it is unknown how this affects regional ventricular function. This study investigated the impact of transthoracic electrical shocks on systolic and diastolic myocardial deformation. Ten healthy anaesthetized female swine received five transthoracic shocks (5 × 200 J) and six controls underwent a cardiovascular magnetic resonance exam prior to and 5 h after the intervention. Serial transthoracic shocks led to a global reduction in both left (LV, - 15.6 ± 3.3% to - 13.0 ± 3.6%, p < 0.01) and right ventricular (RV, - 16.1 ± 2.3% to - 12.8 ± 4.2%, p = 0.03) peak circumferential strain as a marker of systolic function and to a decrease in LV early diastolic strain rate (1.19 ± 0.35/s to 0.95 ± 0.37/s, p = 0.02), assessed by feature tracking analysis. The extent of myocardial edema (ΔT1) was related to an aggravation of regional LV and RV diastolic dysfunction, whereas only RV systolic function was regionally associated with an increase in T1. In conclusion, serial transthoracic shocks in a healthy swine model attenuate biventricular systolic function, but it is the acute development of regional diastolic dysfunction that is associated with the onset of colocalized myocardial edema.

Time in Therapeutic Range With Vitamin K Antagonists in Congenital Heart Disease: A Multicentre Study.

BACKGROUND: Vitamin K antagonists (VKAs) are frequently prescribed to patients with congenital heart disease (CHD) for atrial arrhythmias or Fontan palliation, but there is a paucity of data regarding time spent in the therapeutic range (TTR). We sought to determine the TTR in patients with CHD and atrial arrhythmias or Fontan palliation prescribed VKAs and explore associations with thromboembolic and bleeding events. METHODS: A multicentre North American cohort study was conducted on patients with CHD who received VKAs for sustained atrial arrhythmia or Fontan palliation. TTR was calculated using the Rosendaal linear interpolation method. Generalized estimating equations were used to explore factors associated with time outside the therapeutic range. RESULTS: A total of 567 patients, aged 33 ± 17 years, 56% female, received VKAs for 11.5 ± 8.4 years for atrial arrhythmias (63.0%) or Fontan palliation (58.0%). CHD was simple, moderate, and complex in 10.8%, 20.3%, and 69.0%, respectively. Site investigators perceived good control over international normalized ratio (INR) levels in most patients (75.3%), with no or minor compliance or adherence issues (85.6%). The mean TTR was 41.9% (95% confidence interval [CI], 39.0%-44.8%). Forty-seven (8.3%) and 34 (6.0%) patients had thromboembolic and bleeding events, respectively. Thromboembolic events were associated with a higher proportion of time below the therapeutic range (31.3% vs 19.1%, P = 0.003) and bleeding complications with a higher proportion of time above the therapeutic range (32.5% vs 19.5%, P = 0.006). CONCLUSIONS: Patients with CHD who receive VKAs spend < 42% of their time with INR levels in the therapeutic range, with repercussions regarding thromboembolic and bleeding complications.

The Fontan Circulation: From Ideal to Failing Hemodynamics and Drug Therapies for Optimization.

Fontan palliation results in a hemodynamically complex circulation with multisystem consequences, which in the long term adversely affect many body processes. Systemic venous hypertension, nonpulsatile low-shear pulmonary blood flow, and low cardiac output are the 3 main characteristics of a Fontan circulation, leading to unavoidable slowly progressive failure. An appreciation of how the hemodynamics of a Fontan circulation change with time and relate to the various modes of Fontan circulatory failure is important. Accurate hemodynamic assessment aid this understanding and may permit early identification of potentially treatable drivers of decline. While no evidence-based or guideline-directed pharmacologic management strategy has been established in Fontan patients, understanding the hemodynamics of Fontan circulation failure will assist in the rational selection of potentially helpful drug therapies for individual patients. In this review, we present hemodynamic concepts of the optimal Fontan physiology and Fontan circulatory failure, review practical aspects of invasive hemodynamic assessment, and discuss the role of drug therapies in increasing systemic venous blood flow return and decreasing ventricular filling pressures in Fontan circulation. Often complementary to catheter-based or surgical interventions, pharmacologic management aims at preserving patency of the circuit, adequate systolic and diastolic ventricular function, atrioventricular valve function, an unobstructed ventricular outflow tract, and pulmonary vascular integrity in order to maintain an acceptable cardiac output.

Autograft remodeling after the Ross procedure by cardiovascular magnetic resonance imaging: Aortic stenosis versus insufficiency.

BACKGROUND: Studies suggest that patients undergoing the Ross procedure for aortic insufficiency are at greater risk of autograft dilatation than those with aortic stenosis. By using a tailored Ross technique to mitigate autograft dilatation in patients with aortic insufficiency, we aimed to compare the biomechanical and morphologic remodeling of the autograft at 1 year between patients with aortic insufficiency and patients with aortic stenosis. METHODS: A total of 210 patients underwent a Ross procedure (2011-2016). Of those, 86 patients (mean age 43 ± 13 years; 32% were female) completed preoperative and postoperative cardiovascular magnetic resonance imaging. A total of 71 studies were suitable for analysis: 41 patients with aortic stenosis and 30 patients with aortic insufficiency. Nine healthy adults were used as controls. Autograft root dimensions, individual sinus volumes, and distensibility were measured using cardiovascular magnetic resonance. RESULTS: At 1 year, there was no difference in autograft root dimensions between patients with aortic stenosis (mean annulus 25.1 ± 3.1 mm and sinus diameters 35 ± 4.1 mm) and patients with aortic insufficiency (26.6 ± 3 mm and 37.1 ± 3.5 mm; P = .12 and .06, respectively). Relative sinus of Valsalva volumes were symmetrical in the aortic stenosis (right 34.8% ± 4%, left 33.7% ± 3.5%, noncoronary 31.4% ± 3.2%) and aortic insufficiency groups (34.8% ± 3.9%, 33.8% ± 2.8%, 31.3% ± 3.7%, P = .85, .92, and .82), and similar to those of healthy adults. Aortic root distensibility was reduced in both groups compared with healthy adults (P = .003), but was similar between aortic stenosis (3.12 ± 1.58 × 10-3 mm Hg-1) and aortic insufficiency (3.04 ± 1.15 × 10-3 mm Hg-1; P = .9). CONCLUSIONS: Using a tailored technique, there were no differences in the morphologic or biomechanical remodeling of the autograft root 1 year after the Ross procedure between patients with aortic stenosis and patients with aortic insufficiency. However, autograft roots are stiffer than native aortic roots.

Perinatal and cardiac outcomes of women with hypertrophic cardiomyopathy.

RATIONALE: Pregnancy causes important physiologic stress for women with hypertrophic cardiomyopathy. Data regarding the impact of this condition on obstetrical outcomes is missing. OBJECTIVES: Our objective was to report obstetrical and cardiac outcomes in pregnant women with hypertrophic cardiomyopathy and to assess the possible adverse effects of left ventricular outflow tract obstruction in pregnancy. STUDY DESIGN: This was a retrospective cohort study of pregnant women diagnosed with HCM and followed at single tertiary center between 1995 and 2019. Demographic, medical and surgical data, echocardiographic parameters, and pregnancy outcomes were abstracted through extensive chart review. Patients were divided into 2 groups: obstructive (maximal left ventricular outflow tract gradient over 30 mmHg) versus non-obstructive hypertrophic cardiomyopathy. Outcomes between groups were compared with t-test, Mann-Whitney and Fisher's exact tests when appropriate. RESULTS: Eighteen women with 27 pregnancies were included. The study population was formed of 18 women with a total of 27 pregnancies that reached at least 20 weeks of gestation: 12 pregnancies in women with obstructive hypertrophic cardiomyopathy and 15 pregnancies in women with non-obstructive hypertrophic cardiomyopathy. Among the non-obstructive hypertrophic cardiomyopathy, 5 of them had been treated for their obstruction. One patient with obstructive hypertrophic cardiomyopathy had a medical termination of pregnancy for uncontrolled arrhythmia at 21 weeks. There were no maternal deaths. Left ventricular outflow tract obstruction was associated with increased cardiac events including arrhythmias and heart failure (5/12 versus 0/15; p = .006). Preterm birth occurred in more than 50% of cases, resulting from induced delivery for a maternal (40%) or fetal reason (60%). Most deliveries were late preterm between 34 and 36 6/7 weeks. In both groups, birthweight was mainly distributed below the 50th percentile (89%) and 35% of neonates were born small for gestational age defined as a birthweight below the 10th percentile. Most severe cases of small for gestational age (birthweight under the 5th percentile) were found in patients with treated obstructive hypertrophic cardiomyopathy. CONCLUSION: Hypertrophic cardiomyopathy is associated with prematurity and small for gestational age. Left ventricular outflow tract obstruction is associated with adverse cardiac events including arrythmias or heart failure. Treated obstructive cardiomyopathy constitutes a sub-group of patients at high risk of severe small for gestational age and deserves a close surveillance. Therefore, fetal growth surveillance with ultrasound, early in the third trimester and doppler studies to assess the utero-placental perfusion in the second and third trimesters are warranted in all patients with hypertrophic cardiomyopathy regardless of the severity of their condition.

Wall stresses of early remodeled pulmonary autografts.

OBJECTIVE: The Ross procedure is an excellent option for children or young adults who need aortic valve replacement because it can restore survival to that of the normal aged-matched population. However, autograft remodeling can lead to aneurysmal formation and reoperation, and the biomechanics of this process is unknown. This study investigated postoperative autograft remodeling after the Ross procedure by examining patient-specific autograft wall stresses. METHODS: Patients who have undergone the Ross procedure who had intraoperative pulmonary root and aortic specimens collected were recruited. Patient-specific models (n = 16) were developed using patient-specific material property and their corresponding geometry from cine magnetic resonance imaging at 1-year follow-up. Autograft ± Dacron for aneurysm repair and ascending aortic geometries were reconstructed to develop patient-specific finite element models, which incorporated material properties and wall thickness experimentally measured from biaxial stretching. A multiplicative approach was used to account for prestress geometry from in vivo magnetic resonance imaging. Pressure loading to systemic pressure (120/80) was performed using LS-DYNA software (LSTC Inc, Livermore, Calif). RESULTS: At systole, first principal stresses were 809 kPa (25%-75% interquartile range, 691-1219 kPa), 567 kPa (485-675 kPa), 637 kPa (555-755 kPa), and 382 kPa (334-413 kPa) at the autograft sinotubular junction, sinuses, annulus, and ascending aorta, respectively. Second principal stresses were 360 kPa (310-426 kPa), 355 kPa (320-394 kPa), 272 kPa (252-319 kPa), and 184 kPa (147-222 kPa) at the autograft sinotubular junction, sinuses, annulus, and ascending aorta, respectively. Mean autograft diameters were 29.9 ± 2.7 mm, 38.3 ± 5.3 mm, and 26.6 ± 4.0 mm at the sinotubular junction, sinuses, and annulus, respectively. CONCLUSIONS: Peak first principal stresses were mainly located at the sinotubular junction, particularly when Dacron reinforcement was used. Patient-specific simulations lay the foundation for predicting autograft dilatation in the future after understanding biomechanical behavior during long-term follow-up.

Validation of cardiac diffusion tensor imaging sequences: A multicentre test-retest phantom study.

Cardiac diffusion tensor imaging (DTI) is an emerging technique for the in vivo characterisation of myocardial microstructure, and there is a growing need for its validation and standardisation. We sought to establish the accuracy, precision, repeatability and reproducibility of state-of-the-art pulse sequences for cardiac DTI among 10 centres internationally. Phantoms comprising 0%-20% polyvinylpyrrolidone (PVP) were scanned with DTI using a product pulsed gradient spin echo (PGSE; N = 10 sites) sequence, and a custom motion-compensated spin echo (SE; N = 5) or stimulated echo acquisition mode (STEAM; N = 5) sequence suitable for cardiac DTI in vivo. A second identical scan was performed 1-9 days later, and the data were analysed centrally. The average mean diffusivities (MDs) in 0% PVP were (1.124, 1.130, 1.113) x 10-3  mm2 /s for PGSE, SE and STEAM, respectively, and accurate to within 1.5% of reference data from the literature. The coefficients of variation in MDs across sites were 2.6%, 3.1% and 2.1% for PGSE, SE and STEAM, respectively, and were similar to previous studies using only PGSE. Reproducibility in MD was excellent, with mean differences in PGSE, SE and STEAM of (0.3 ± 2.3, 0.24 ± 0.95, 0.52 ± 0.58) x 10-5  mm2 /s (mean ± 1.96 SD). We show that custom sequences for cardiac DTI provide accurate, precise, repeatable and reproducible measurements. Further work in anisotropic and/or deforming phantoms is warranted.

Myocardial Vascular Function Assessed by Dynamic Oxygenation-sensitive Cardiac Magnetic Resonance Imaging Long-term Following Cardiac Transplantation.

BACKGROUND: Coronary vascular function is related to adverse outcomes following cardiac transplantation (CTx) in patients with or without cardiac allograft vasculopathy (CAV). The noninvasive assessment of the myocardial vascular response using oxygenation-sensitive cardiac magnetic resonance (OS-CMR has not been investigated in stable long-term CTx recipients). METHODS: CTx patients were prospectively recruited to complete a CMR study with a breathing maneuver of hyperventilation followed by a voluntary apnea. Changes in OS-sensitive signal intensity reflecting the myocardial oxygenation response were monitored and expressed as % change in response to these breathing maneuvers. Myocardial injury was further investigated with T2-weighted imaging, native and postcontrast T1 measurements, extracellular volume measurements, and late gadolinium enhancement. RESULTS: Forty-six CTx patients with (n = 23) and without (n = 23) CAV, along with 25 healthy controls (HC), were enrolled. The OS response was significantly attenuated in CTx compared with HC at the 30-second time-point into the breath-hold (2.63% ± 4.16% versus 6.40% ± 5.96%; P = 0.010). Compared with HC, OS response was lower in CTx without CAV (2.62% ± 4.60%; P < 0.05), while this response was further attenuated in patients with severe CAV (grades 2-3, -2.24% ± 3.65%). An inverse correlation was observed between OS-CMR, ventricular volumes, and diffuse fibrosis measured by extracellular volume mapping. CONCLUSIONS: In heart transplant patients, myocardial oxygenation is impaired even in the absence of CAV suggesting microvascular dysfunction. These abnormalities can be identified by oxygenation-sensitive CMR using simple breathing maneuvers.

Pulmonary Vein Stenosis After Atrial Fibrillation Ablation: Insights From the ADVICE Trial.

BACKGROUND: Pulmonary vein (PV) stenosis is a complication of atrial fibrillation (AF) ablation. The incidence of PV stenosis after routine post-ablation imaging remains unclear and is limited to single-centre studies. Our objective was to determine the incidence and predictors of PV stenosis following circumferential radiofrequency ablation in the multicentre Adenosine Following Pulmonary Vein Isolation to Target Dormant Conduction Elimination (ADVICE) trial. METHODS: Patients with symptomatic AF underwent circumferential radiofrequency ablation in one of 13 trial centres. Computed tomographic (CTA) or magnetic resonance (MRA) angiography was performed before ablation and 90 days after ablation. Two blinded reviewers measured PV diameters and areas. PVs with stenosis were classified as severe (> 70%), moderate (50%-70%), or mild (< 50%). Predictors of PV stenosis were identified by means of multivariable logistic regression. RESULTS: A total of 197 patients (median age 59.5 years, 29.4% women) were included in this substudy. PV stenosis was identified in 41 patients (20.8%) and 47 (8.2%) of 573 ablated PVs. PV stenosis was classified as mild in 42 PVs (7.3%) and moderate in 5 PVs (0.9%). No PVs had severe stenosis. Both cross-sectional area and diameter yielded similar classifications for severity of PV stenosis. Diabetes was associated with a statistically significant increased risk of PV stenosis (OR 4.91, 95% CI 1.45-16.66). CONCLUSIONS: In the first systematic multicentre evaluation of post-ablation PV stenosis, no patient acquired severe PV stenosis. Although the results are encouraging for the safety of AF ablation, 20.8% of patients had mild or moderate PV stenosis, in which the long-term effects are unknown.

A Novel Recurrent COL5A1 Genetic Variant Is Associated With a Dysplasia-Associated Arterial Disease Exhibiting Dissections and Fibromuscular Dysplasia.

OBJECTIVE: While rare variants in the COL5A1 gene have been associated with classical Ehlers-Danlos syndrome and rarely with arterial dissections, recurrent variants in COL5A1 underlying a systemic arteriopathy have not been described. Monogenic forms of multifocal fibromuscular dysplasia (mFMD) have not been previously defined. Approach and Results: We studied 4 independent probands with the COL5A1 pathogenic variant c.1540G>A, p.(Gly514Ser) who presented with arterial aneurysms, dissections, tortuosity, and mFMD affecting multiple arteries. Arterial medial fibroplasia and smooth muscle cell disorganization were confirmed histologically. The COL5A1 c.1540G>A variant is predicted to be pathogenic in silico and absent in gnomAD. The c.1540G>A variant is on a shared 160.1 kb haplotype with 0.4% frequency in Europeans. Furthermore, exome sequencing data from a cohort of 264 individuals with mFMD were examined for COL5A1 variants. In this mFMD cohort, COL5A1 c.1540G>A and 6 additional relatively rare COL5A1 variants predicted to be deleterious in silico were identified and were associated with arterial dissections (P=0.005). CONCLUSIONS: COL5A1 c.1540G>A is the first recurring variant recognized to be associated with arterial dissections and mFMD. This variant presents with a phenotype reminiscent of vascular Ehlers-Danlos syndrome. A shared haplotype among probands supports the existence of a common founder. Relatively rare COL5A1 genetic variants predicted to be deleterious by in silico analysis were identified in ≈2.7% of mFMD cases, and as they were enriched in patients with arterial dissections, may act as disease modifiers. Molecular testing for COL5A1 should be considered in patients with a phenotype overlapping with vascular Ehlers-Danlos syndrome and mFMD.

T1 mapping performance and measurement repeatability: results from the multi-national T1 mapping standardization phantom program (T1MES).

BACKGROUND: The T1 Mapping and Extracellular volume (ECV) Standardization (T1MES) program explored T1 mapping quality assurance using a purpose-developed phantom with Food and Drug Administration (FDA) and Conformité Européenne (CE) regulatory clearance. We report T1 measurement repeatability across centers describing sequence, magnet, and vendor performance. METHODS: Phantoms batch-manufactured in August 2015 underwent 2 years of structural imaging, B0 and B1, and "reference" slow T1 testing. Temperature dependency was evaluated by the United States National Institute of Standards and Technology and by the German Physikalisch-Technische Bundesanstalt. Center-specific T1 mapping repeatability (maximum one scan per week to minimum one per quarter year) was assessed over mean 358 (maximum 1161) days on 34 1.5 T and 22 3 T magnets using multiple T1 mapping sequences. Image and temperature data were analyzed semi-automatically. Repeatability of serial T1 was evaluated in terms of coefficient of variation (CoV), and linear mixed models were constructed to study the interplay of some of the known sources of T1 variation. RESULTS: Over 2 years, phantom gel integrity remained intact (no rips/tears), B0 and B1 homogenous, and "reference" T1 stable compared to baseline (% change at 1.5 T, 1.95 ± 1.39%; 3 T, 2.22 ± 1.44%). Per degrees Celsius, 1.5 T, T1 (MOLLI 5s(3s)3s) increased by 11.4 ms in long native blood tubes and decreased by 1.2 ms in short post-contrast myocardium tubes. Agreement of estimated T1 times with "reference" T1 was similar across Siemens and Philips CMR systems at both field strengths (adjusted R2 ranges for both field strengths, 0.99-1.00). Over 1 year, many 1.5 T and 3 T sequences/magnets were repeatable with mean CoVs < 1 and 2% respectively. Repeatability was narrower for 1.5 T over 3 T. Within T1MES repeatability for native T1 was narrow for several sequences, for example, at 1.5 T, Siemens MOLLI 5s(3s)3s prototype number 448B (mean CoV = 0.27%) and Philips modified Look-Locker inversion recovery (MOLLI) 3s(3s)5s (CoV 0.54%), and at 3 T, Philips MOLLI 3b(3s)5b (CoV 0.33%) and Siemens shortened MOLLI (ShMOLLI) prototype 780C (CoV 0.69%). After adjusting for temperature and field strength, it was found that the T1 mapping sequence and scanner software version (both P < 0.001 at 1.5 T and 3 T), and to a lesser extent the scanner model (P = 0.011, 1.5 T only), had the greatest influence on T1 across multiple centers. CONCLUSION: The T1MES CE/FDA approved phantom is a robust quality assurance device. In a multi-center setting, T1 mapping had performance differences between field strengths, sequences, scanner software versions, and manufacturers. However, several specific combinations of field strength, sequence, and scanner are highly repeatable, and thus, have potential to provide standardized assessment of T1 times for clinical use, although temperature correction is required for native T1 tubes at least.