Prognostic value of strain by feature-tracking cardiac magnetic resonance in arrhythmogenic right ventricular cardiomyopathy

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by ventricular dysfunction and ventricular arrhythmias (VA). Adequate arrhythmic risk assessment is important to prevent sudden cardiac death. We aimed to study the incremental value of strain by feature-tracking cardiac magnetic resonance imaging (FT-CMR) in predicting sustained VA in ARVC patients. METHODS AND RESULTS: CMR images of 132 ARVC patients (43% male, 40.6 ± 16.0 years) without prior VA were analysed for global and regional right and left ventricular (RV, LV) strain. Primary outcome was sustained VA during follow-up. We performed multivariable regression assessing strain, in combination with (i) RV ejection fraction (EF); (ii) LVEF; and (iii) the ARVC risk calculator. False discovery rate adjusted P-values were given to correct for multiple comparisons and c-statistics were calculated for each model. During 4.3 (2.0-7.9) years of follow-up, 19% of patients experienced sustained VA. Compared to patients without VA, those with VA had significantly reduced RV longitudinal (P ≤ 0.03) and LV circumferential (P ≤ 0.04) strain. In addition, patients with VA had significantly reduced biventricular EF (P ≤ 0.02). After correcting for RVEF, LVEF, and the ARVC risk calculator separately in multivariable analysis, both RV and LV strain lost their significance [hazard ratio 1.03-1.18, P > 0.05]. Likewise, while strain improved the c-statistic in combination with RVEF, LVEF, and the ARVC risk calculator separately, this did not reach statistical significance (P ≥ 0.18). CONCLUSION: Both RV longitudinal and LV circumferential strain are reduced in ARVC patients with sustained VA during follow-up. However, strain does not have incremental value over RVEF, LVEF, and the ARVC VA risk calculator

Patient-Specific Computational Modeling of Upper Extremity Arteriovenous Fistula Creation: Its Feasibility to Support Clinical Decision-Making

<div><h3>Introduction</h3><p>Inadequate flow enhancement on the one hand, and excessive flow enhancement on the other hand, remain frequent complications of arteriovenous fistula (AVF) creation, and hamper hemodialysis therapy in patients with end-stage renal disease. In an effort to reduce these, a patient-specific computational model, capable of predicting postoperative flow, has been developed. The purpose of this study was to determine the accuracy of the patient-specific model and to investigate its feasibility to support decision-making in AVF surgery.</p> <h3>Methods</h3><p>Patient-specific pulse wave propagation models were created for 25 patients awaiting AVF creation. Model input parameters were obtained from clinical measurements and literature. For every patient, a radiocephalic AVF, a brachiocephalic AVF, and a brachiobasilic AVF configuration were simulated and analyzed for their postoperative flow. The most distal configuration with a predicted flow between 400 and 1500 ml/min was considered the preferred location for AVF surgery. The suggestion of the model was compared to the choice of an experienced vascular surgeon. Furthermore, predicted flows were compared to measured postoperative flows.</p> <h3>Results</h3><p>Taken into account the confidence interval (25^th and 75^th percentile interval), overlap between predicted and measured postoperative flows was observed in 70% of the patients. Differentiation between upper and lower arm configuration was similar in 76% of the patients, whereas discrimination between two upper arm AVF configurations was more difficult. In 3 patients the surgeon created an upper arm AVF, while model based predictions allowed for lower arm AVF creation, thereby preserving proximal vessels. In one patient early thrombosis in a radiocephalic AVF was observed which might have been indicated by the low predicted postoperative flow.</p> <h3>Conclusions</h3><p>Postoperative flow can be predicted relatively accurately for multiple AVF configurations by using computational modeling. This model may therefore be considered a valuable additional tool in the preoperative work-up of patients awaiting AVF creation.</p> </div

Variant location is a novel risk factor for individuals with arrhythmogenic cardiomyopathy due to a desmoplakin (DSP) truncating variant.

BACKGROUND: Truncating variants in desmoplakin (DSPtv) are an important cause of arrhythmogenic cardiomyopathy; however the genetic architecture and genotype-specific risk factors are incompletely understood. We evaluated phenotype, risk factors for ventricular arrhythmias, and underlying genetics of DSPtv cardiomyopathy. METHODS: Individuals with DSPtv and any cardiac phenotype, and their gene-positive family members were included from multiple international centers. Clinical data and family history information were collected. Event-free survival from ventricular arrhythmia was assessed. Variant location was compared between cases and controls, and literature review of reported DSPtv performed. RESULTS: There were 98 probands and 72 family members (mean age at diagnosis 43±8 years, 59% women) with a DSPtv, of which 146 were considered clinically affected. Ventricular arrhythmia (sudden cardiac arrest, sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator therapy) occurred in 56 (33%) individuals. DSPtv location and proband status were independent risk factors for ventricular arrhythmia. Further, gene region was important with variants in cases (cohort n=98; Clinvar n=167) more likely to occur in the regions resulting in nonsense mediated decay of both major DSP isoforms, compared with n=124 genome aggregation database control variants (148 [83.6%] versus 29 [16.4%]; P<0.0001). CONCLUSIONS: In the largest series of individuals with DSPtv, we demonstrate that variant location is a novel risk factor for ventricular arrhythmia, can inform variant interpretation, and provide critical insights to allow for precision-based clinical management

The Netherlands Arrhythmogenic Cardiomyopathy Registry: design and status update

Background Clinical research on arrhythmogenic cardiomyopathy (ACM) is typically limited by small patient numbers, retrospective study designs, and inconsistent definitions. Aim To create a large national ACM patient cohort with a vast amount of uniformly collected high-quality data that is readily available for future research. Methods This is a multicentre, longitudinal, observational cohort study that includes (1) patients with a definite ACM diagnosis, (2) at-risk relatives of ACM patients, and (3) ACM-associated mutation carriers. At baseline and every follow-up visit, a medical history as well information regarding (non-)invasive tests is collected (e. g. electrocardiograms, Holter recordings, imaging and electrophysiological studies, pathology reports, etc.). Outcome data include (non-)sustained ventricular and atrial arrhythmias, heart failure, and (cardiac) death. Data are collected on a research electronic data capture (REDCap) platform in which every participating centre has its own restricted data access group, thus empowering local studies while facilitating data sharing. Discussion The Netherlands ACM Registry is a national observational cohort study of ACM patients and relatives. Prospective and retrospective data are obtained at multiple time points, enabling both cross-sectional and longitudinal research in a hypothesis-generating approach that extends beyond one specific research question. In so doing, this registry aims to (1) increase the scientific knowledge base on disease mechanisms, genetics, and novel diagnostic and treatment strategies of ACM; and (2) provide education for physicians and patients concerning ACM, e. g. through our website (www.acmregistry.nl) and patient conferences

Retrograde catheterization of haemodialysis fistulae and grafts: angiographic depiction of the entire vascular access tree and stenosis treatment

Background. The European Best Practice Guidelines on Vascular Access propose magnetic resonance angiography (MRA) of dysfunctional dialysis fistulae and grafts if visualization of the complete arterial inflow and outflow vessels is needed. In a prospective multi-centre study we determined the technical success rate of complete vascular access tree depiction by digital subtraction angiography (DSA) as an alternative to MRA. Instead of a more invasive brachial artery of femoral artery approach, we performed a retrograde catheterization of the venous outflow or graft, and stenoses were treated in connection with DSA. Methods. A catheter was advanced into the central arterial inflow after retrograde puncture of the venous outflow or graft for depiction of the complete inflow, access region and complete outflow. Access DSA through femoral artery puncture was done if the retrograde approach failed to depict the complete vascular access tree. Stenoses with a luminal diameter reduction >= 50% were treated, if possible, in connection with DSA. Results. A total of 116 dysfunctional haemodialysis fistulae and 50 grafts were included. Retrograde DSA depicted the complete vascular tree in 162 patients (97.6%). The arteriovenous anastomosis of four fistulae could not be negotiated by a catheter. DSA demonstrated 247 significant stenoses: 30, 128 and 89 were located in the arterial inflow (12.1%), AV anastomosis and graft region (51.8%) and venous outflow (36.0%), respectively. Ten patients (6.0%) had no stenosis. Eight (4.8%), 55 (33.1%) and 33 (19.9%) patients demonstrated stenoses in only inflow, access region or outflow, respectively. Stenoses in two or three vascular territories were present in 53 (31.9%) and 7 (4.2%) patients, respectively. A technically successful endovascular intervention was obtained in 135 of the 139 patients (97.1%) who underwent angioplasty and/or stent placement. Additional sheath insertion by antegrade outflow puncture was needed in 46 patients (33.1%) for the treatment of coexisting venous outflow stenoses, located downstream from the retrograde positioned sheath. Two minor complications were observed at DSA/angioplasty. Conclusion. As an alternative to MRA, full retrograde DSA is safe and effective for stenosis detection and stenosis treatment. However, access evaluation by a non-invasive imaging modality such as colour duplex ultrasound will be sufficient in most cases as proximal inflow stenoses are encountered in a minority of patients. Full retrograde DSA, including complete arterial inflow depiction, may then be reserved for cases with an unsuccessful outcome following endovascular intervention of stenoses depicted at ultrasound

Automatic segmentation of the aortic root in CT angiography of candidate patients for transcatheter aortic valve implantation

Transcatheter aortic valve implantation is a minimal-invasive intervention for implanting prosthetic valves in patients with aortic stenosis. Accurate automated sizing for planning and patient selection is expected to reduce adverse effects such as paravalvular leakage and stroke. Segmentation of the aortic root in CTA is pivotal to enable automated sizing and planning. We present a fully automated segmentation algorithm to extract the aortic root from CTA volumes consisting of a number of steps: first, the volume of interest is automatically detected, and the centerline through the ascending aorta and aortic root centerline are determined. Subsequently, high intensities due to calcifications are masked. Next, the aortic root is represented in cylindrical coordinates. Finally, the aortic root is segmented using 3D normalized cuts. The method was validated against manual delineations by calculating Dice coefficients and average distance error in 20 patients. The method successfully segmented the aortic root in all 20 cases. The mean Dice coefficient was 0.95 ± 0.03, and the mean radial absolute error was 0.74 ± 0.39 mm, where the interobserver Dice coefficient was 0.95 ± 0.03 and the mean error was 0.68 ± 0.34¿mm. The proposed algorithm showed accurate results compared to manual segmentations