R. Nils Planken

SCN5A Mutations in Brugada Syndrome Are Associated with Increased Cardiac Dimensions and Reduced Contractility

Background The cardiac sodium channel (Nav1.5) controls cardiac excitability. Accordingly, SCN5A mutations that result in loss-of-function of Nav1.5 are associated with various inherited arrhythmia syndromes that revolve around reduced cardiac excitability, most notably Brugada syndrome (BrS). Experimental studies have indicated that Nav1.5 interacts with the cytoskeleton and may also be involved in maintaining structural integrity of the heart. We aimed to determine whether clinical evidence may be obtained that Nav1.5 is involved in maintaining cardiac structural integrity. Methods Using cardiac magnetic resonance (CMR) imaging, we compared right ventricular (RV) and left ventricular (LV) dimensions and ejection fractions between 40 BrS patients with SCN5A mutations (SCN5a-mut-positive) and 98 BrS patients without SCN5A mutations (SCN5a-mut-negative). We also studied 18 age/sex-matched healthy volunteers. Results SCN5a-mut-positive patients had significantly larger end-diastolic and end-systolic RV and LV volumes, and lower LV ejection fractions, than SCN5a-mut-negative patients or volunteers. Conclusions Loss-of-function SCN5A mutations are associated with dilatation and impairment in contractile function of both ventricles that can be detected by CMR analysis.

Stenosis detection in forearm hemodialysis arteriovenous fistulae by multiphase contrast-enhanced magnetic resonance angiography: preliminary experience.

To assess the feasibility and accuracy of multiphase contrast‐enhanced magnetic resonance angiography (CE‐MRA) in patients with dysfunctioning hemodialysis arteriovenous fistulae (AVF), using digital subtraction angiography (DSA) as the standard of reference.

Clinical study protocol for the ARCH project - Computational modeling for improvement of outcome after vascular access creation

Despite clinical guidelines and the possibility of diagnostic vascular imaging, creation and maintenance of a vascular access (VA) remains problematic: avoiding short- and long-term VA dysfunction is challenging. Although prognostic factors for VA dysfunction have been identified in previous studies, their potential interplay at a systemic level is disregarded. Consideration of multiple prognostic patient specific factors and their complex interaction using dedicated computational modeling tools might improve outcome after VA creation by enabling a better selection of VA configuration. These computational modeling tools are developed and validated in the ARCH project: a joint initiative of four medical centers and three industrial partners (FP7-ICT-224390). This paper reports the rationale behind computational modeling and presents the clinical study protocol designed for calibrating and validating these modeling tools. The clinical study is based on the pre-operative collection of structural and functional data at a vascular level, as well as a VA functional evaluation during the follow-up period. The strategy adopted to perform the study and for data collection is also described here.

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

Introduction 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. Methods 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. Results Taken into account the confidence interval (25th and 75th 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. Conclusions 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.

The hypertrabeculated (noncompacted) left ventricle is different from the ventricle of embryos and ectothermic vertebrates

Ventricular hypertrabeculation (noncompaction) is a poorly characterized condition associated with heart failure. The condition is widely assumed to be the retention of the trabeculated ventricular design of the embryo and ectothermic (cold-blooded) vertebrates. This assumption appears simplistic and counterfactual. Here, we measured a set of anatomical parameters in hypertrabeculation in man and in the ventricles of embryos and animals. We compared humans with left ventricular hypertrabeculation (N=21) with humans with structurally normal left ventricles (N=54). We measured ejection fraction and ventricular trabeculation using cardiovascular MRI. Ventricular trabeculation was further measured in series of embryonic human and 9 animal species, and in hearts of 15 adult animal species using MRI, CT, or histology. In human, hypertrabeculated left ventricles were significantly different from structurally normal left ventricles by all structural measures and ejection fraction. They were far less trabeculated than human embryonic hearts (15-40% trabeculated volume versus 55-80%). Early in development all vertebrate embryos acquired a ventricle with approximately 80% trabeculations, but only ectotherms retained the 80% trabeculation throughout development. Endothermic (warm-blooded) animals including human slowly matured in fetal and postnatal stages towards ventricles with little trabeculations, generally less than 30%. Further, the trabeculations of all embryos and adult ectotherms were very thin, less than 50 μm wide, whereas the trabeculations in adult endotherms and in the setting of hypertrabeculation were wider by orders of magnitude. It is concluded in contrast to a prevailing assumption, the hypertrabeculated left ventricle is not like the ventricle of the embryo or of adult ectotherms. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

Aortic valve calcification as a predictor of location and severity of paravalvular regurgitation after transcatheter aortic valve implantation

OBJECTIVES To determine whether the location of aortic valve calcium (AVC) influences the location of paravalvular regurgitation (PR). PR is an adverse effect of transcatheter aortic valve implantation (TAVI) with a negative effect on long-term patient survival. The relationship between AVC and the occurrence of PR has been documented. However, the relationship between the distribution of AVC and the location of PR is still sparsely studied. The purpose of this study was to correlate severity and location of AVC with PR in patients treated with TAVI. METHODS Fifty-six consecutive patients who underwent transaortic or transapical TAVI and had preoperative computed tomography scans were included in this retrospective study. The volume, mass and location of AVC was determined and compared between patients with and without PR using a non-parametric t-test. Postoperative echocardiography was performed to determine the presence and location of PR, which was associated with the cusp with highest AVC using a χ(2) test. RESULTS Valve deployment was successful in all 56 patients. PR was present in 38 patients (68%) after TAVI. There was a non-significantly higher volume of AVC in the PR group [214 (70-418) vs 371 (254-606) cm(3), P = 0.15]. AVC mass was significantly higher in patients with PR than in patients without PR [282 (188-421) vs 142 (48-259) mg, respectively, P = 0.043]. The location of PR was determined in 36 of these patients. Of these 36 patients, PR occurred at the cusp with the highest AVC in 20 patients (56%, χ(2) P = 0.030). CONCLUSIONS In our population, PR was associated with greater AVC mass. Moreover, the location of PR was associated with the cusp with the highest amount of AVC.

B-Mode Sonographic Assessment of the Posterior Circumflex Humeral Artery The SPI-US Protocol—A Technical Procedure in 4 Steps

Elite overhead athletes are at risk of vascular injury due to repetitive abduction and external rotation of the dominant arm. The posterior circumflex humeral artery (PCHA) is prone to degeneration, aneurysm formation, and thrombosis in elite volleyball players and baseball pitchers. The prevalence of PCHA‐related thromboembolic complications is unknown in this population. However, the prevalence of symptoms associated with digital ischemia is 31% in elite volleyball players. A standardized noninvasive imaging tool will aid in early detection of PCHA injury, prevention of thromboembolic complications, and measurement reproducibility. A standardized vascular sonographic protocol for assessment of the proximal PCHA (SPI‐US protocol [Shoulder PCHA Pathology and Digital Ischemia–Ultrasound protocol]) is presented.

Additional diagnostic value of CMR to the European Society of Cardiology (ESC) position statement criteria in a large clinical population of patients with suspected myocarditis

Aims To determine the diagnostic yield of tissue characterization by cardiovascular magnetic resonance (CMR) in a large clinical population of patients with suspected acute myocarditis (AM) and to establish its diagnostic value within the 2013 European Society of Cardiology position statement criteria (ESC-PSC) for clinically suspected myocarditis. Methods and results In this retrospective study, CMR examinations of 303 hospitalized patients referred for work-up of suspected AM in two tertiary referral centres were analysed. CMR was performed at median 7 days (interquartile range 4-20 days) after clinical presentation and included cine imaging, T2-weighted imaging, and late gadolinium enhancement. CMR images were evaluated to assign each patient to a diagnosis. By using non-CMR criteria only, the 2013 ESC-PSC were positive for suspected myocarditis in 151 patients and negative in 30. In the remaining 122 patients, there was insufficient information available for ESC-PSC assessment, mostly due to lack of coronary angiography (CAG) before the CMR examination (n = 116, 95%). There were no in-hospital deaths. CMR provided a diagnosis in 158 patients (52%), including myocarditis in 104 (34%), myocardial infarction in 44 (15%), and other pathology in 10 patients (3%). Non-urgent CAG (>24 h after presentation) was performed before the CMR examination in 85 patients, of which 20 (24%) were done in patients with subsequently confirmed AM, which could potentially have been avoided if CMR was performed first. ESC-PSC was correct in diagnosing AM before the CMR in 50 of the 151 patients (33%) and was correct in ruling out AM in all the 30 patients (100%). However, ESC-PSC provided an incorrect diagnosis of AM in 27 of the 151 patients (18%), which was corrected by CMR through the identification of new cardiac disease that could explain the clinical syndrome. Patients with insufficient ESC-PSC information had a relatively low pre-test probability of coronary artery disease. In this group, CMR confirmed the diagnosis of AM in a relatively high percentage (44%) but still revealed myocardial infarction in 8% of them. Conclusion Tissue characterization by CMR provided a good diagnostic yield in this large clinical population of patients with suspected AM. CMR provided incremental diagnostic value to the ESC-PSC by ruling out the diagnosis of AM on one hand and by potentially sparing AM patients from CAG on the other.

Determination of brachial artery stiffness prior to vascular access creation: reproducibility of pulse wave velocity assessment

BACKGROUND Despite routine ultrasound mapping of upper extremity arteries and veins, early thrombosis and nonmaturation remain frequent complications following vascular access (VA) surgery. Besides vascular diameters, brachial artery stiffness is assumed to play an important role; however, reproducibility of measurements has never been established. The purpose of this study was to determine within-session and between-session variabilities of pulse wave velocity (PWV) assessment by using ultrasonography and blood pressure registration. METHODS Beat-to-beat changes in brachial artery diameter and pressure were obtained in 21 subjects in measurement sessions on Day 1 and Day 3. Each session consisted of three acquisitions. For each acquisition, systolic and diastolic diameter and pressure were determined and used for calculation of brachial artery PWV. Within-session variability of diameter and pressure, as well as the estimated PWV, was expressed using the intraclass correlation coefficient with corresponding coefficient of variation (CoV). Between-session variability was reported using Bland-Altman analysis in combination with CoV analysis. RESULTS Significant agreement (P < 0.001) was obtained for all diameter and pressure measurements obtained on Day 1 and Day 3. Within-session CoV of pulse pressure, diastolic diameter and distension were 7.0, 1.6 and 18.3%, respectively. Subsequent estimation of local PWV resulted in a CoV of 10.6%. Between-session CoV was 15.1, 3.8 and 18.9% for pulse pressure, diastolic diameter and distension, respectively. For PWV estimation, this resulted in a CoV of 13.5%. CONCLUSIONS Diameter and pressure can be recorded accurately over the cardiac cycle, and calculations of distensibility, pulse pressure and PWV show a slight to moderate degree of variation. Larger studies elaborating on interindividual differences need to determine the clinical efficacy of PWV measurements prior to VA creation.

Aortic valve stenosis and aortic diameters determine the extent of increased wall shear stress in bicuspid aortic valve disease: AS and Aortic Diameters Determine WSS in BAV

Use of 4‐dimensional flow magnetic resonance imaging (4D‐flow MRI) derived wall shear stress (WSS) heat maps enables identification of regions in the ascending aorta with increased WSS. These regions are subject to dysregulation of the extracellular matrix and elastic fiber degeneration, which is associated with aortic dilatation and dissection.