Investigation of hemodynamics in an in vitro system simulating left ventricular support through the right subclavian artery using 4-dimensional flow magnetic resonance imaging.

OBJECTIVES Left ventricular assist devices are an important treatment option for patients with heart failure alter the hemodynamics in the heart and great vessels. Because in vivo magnetic resonance studies of patients with ventricular assist devices are not possible, in vitro models represent an important tool to investigate flow alterations caused by these systems. By using an in vitro magnetic resonance-compatible model that mimics physiologic conditions as close as possible, this work investigated the flow characteristics using 4-dimensional flow-sensitive magnetic resonance imaging of a left ventricular assist device with outflow via the right subclavian artery as commonly used in cardiothoracic surgery in the recent past. METHODS An in vitro model was developed consisting of an aorta with its supra-aortic branches connected to a left ventricular assist device simulating the pulsatile flow of the native failing heart. A second left ventricular assist device supplied the aorta with continuous flow via the right subclavian artery. Four-dimensional flow-sensitive magnetic resonance imaging was performed for different flow rates of the left ventricular assist device simulating the native heart and the left ventricular assist device providing the continuous flow. Flow characteristics were qualitatively and quantitatively evaluated in the entire vessel system. RESULTS Flow characteristics inside the aorta and its upper branching vessels revealed that the right subclavian artery and the right carotid artery were solely supported by the continuous-flow left ventricular assist device for all flow rates. The flow rates in the brain-supplying arteries are only marginally affected by different operating conditions. The qualitative analysis revealed only minor effects on the flow characteristics, such as weakly pronounced vortex flow caused by the retrograde flow via the brachiocephalic artery. CONCLUSIONS The results indicate that, despite the massive alterations in natural hemodynamics due to the retrograde flow via the right subclavian and brachiocephalic arteries, there are no drastic consequences on the flow in the brain-feeding arteries and the flow characteristics in the ascending and descending aortas. It may be beneficial to adjust the operating condition of the left ventricular assist device to the residual function of the failing heart.

Dissecting abdominal aortic aneurysm in Angiotensin II-infused mice: the importance of imaging

INTRODUCTION Since the initial publication in 2000, Angiotensin II-infused mice have become one of the most popular models to study abdominal aortic aneurysm in a pre-clinical setting. We recently used phase contrast X-ray based computed tomography to demonstrate that these animals develop an apparent luminal dilatation and an intramural hematoma, both related to mural ruptures in the tunica media in the vicinity of suprarenal side branches. AIMS The aim of this narrative review was to provide an extensive overview of small animal applicable techniques that have provided relevant insight into the pathogenesis and morphology of dissecting AAA in mice, and to relate findings from these techniques to each other and to our recent PCXTM-based results. Combining insights from recent and consolidated publications we aimed to enhance our understanding of dissecting AAA morphology and anatomy. RESULTS AND CONCLUSION We analyzed in vivo and ex vivo images of aortas obtained from macroscopic anatomy, histology, high-frequency ultrasound, contrast-enhanced micro-CT, micro-MRI and PCXTM. We demonstrate how in almost all publications the aorta has been subdivided into a part in which an intact lumen lies adjacent to a remodeled wall/hematoma, and a part in which elastic lamellae are ruptured and the lumen appears to be dilated. We show how the novel paradigm fits within the existing one, and how 3D images can explain and connect previously published 2D structures. We conclude that PCXTM-based findings are in line with previous results, and all evidence points towards the fact that dissecting AAAs in Angiotensin II-infused mice are actually caused by ruptures of the tunica media in the immediate vicinity of small side branches.

Myocardial expression profiles of candidate molecules in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia compared to those with dilated cardiomyopathy and healthy controls.

BACKGROUND Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is mainly an autosomal dominant disease characterized by fibrofatty infiltration of the right ventricle, leading to ventricular arrhythmias. Mutations in desmosomal proteins can be identified in about half of the patients. The pathogenic mechanisms leading to disease expression remain unclear. OBJECTIVE The purpose of this study was to investigate myocardial expression profiles of candidate molecules involved in the pathogenesis of ARVC/D. METHODS Myocardial messenger RNA (mRNA) expression of 62 junctional molecules, 5 cardiac ion channel molecules, 8 structural molecules, 4 apoptotic molecules, and 6 adipogenic molecules was studied. The averaged expression of candidate mRNAs was compared between ARVC/D samples (n = 10), nonfamilial dilated cardiomyopathy (DCM) samples (n = 10), and healthy control samples (n = 8). Immunohistochemistry and quantitative protein expression analysis were performed. Genetic analysis using next generation sequencing was performed in all patients with ARVC/D. RESULTS Following mRNA levels were significantly increased in patients with ARVC/D compared to those with DCM and healthy controls: phospholamban (P ≤ .001 vs DCM; P ≤ .001 vs controls), healthy tumor protein 53 apoptosis effector (P = .001 vs DCM; P ≤ .001 vs controls), and carnitine palmitoyltransferase 1β (P ≤ .001 vs DCM; P = 0.008 vs controls). Plakophillin-2 (PKP-2) mRNA was downregulated in patients with ARVC/D with PKP-2 mutations compared with patients with ARVC/D without PKP-2 mutations (P = .04). Immunohistochemistry revealed significantly increased protein expression of phospholamban, tumor protein 53 apoptosis effector, and carnitine palmitoyltransferase 1β in patients with ARVC/D and decreased PKP-2 expression in patients with ARVC/D carrying a PKP-2 mutation. CONCLUSION Changes in the expression profiles of sarcolemmal calcium channel regulation, apoptosis, and adipogenesis suggest that these molecular pathways may play a critical role in the pathogenesis of ARVC/D, independent of the underlying genetic mutations.

Exaggerated pulmonary hypertension and right ventricular dysfunction in high-altitude dwellers with patent foramen ovale.

BACKGROUND There is considerable interindividual variability in pulmonary artery pressure among high-altitude (HA) dwellers, but the underlying mechanism is not known. At low altitude, a patent foramen ovale (PFO) is present in about 25% of the general population. Its prevalence is increased in clinical conditions associated with pulmonary hypertension and arterial hypoxemia, and it is thought to aggravate these problems. METHODS We searched for a PFO (transesophageal echocardiography) in healthy HA dwellers (n = 22) and patients with chronic mountain sickness (n = 35) at 3,600 m above sea level and studied its effects (transthoracic echocardiography) on right ventricular (RV) function, pulmonary artery pressure, and vascular resistance at rest and during mild exercise (50 W), an intervention designed to further increase pulmonary artery pressure. RESULTS The prevalence of PFO (32%) was similar to that reported in low-altitude populations and was not different in participants with and without chronic mountain sickness. Its presence was associated with RV enlargement at rest and an exaggerated increase in right-ventricular-to-right-atrial pressure gradient (25 ± 7 mm Hg vs 15 ± 9 mm Hg, P < .001) and a blunted increase in fractional area change of the right ventricle (3% [-1%, 5%] vs 7% [3%, 16%], P = .008) during mild exercise. CONCLUSIONS These findings show, we believe for the first time, that although the prevalence of PFO is not increased in HA dwellers, its presence appears to facilitate pulmonary vasoconstriction and RV dysfunction during a mild physical effort frequently associated with daily activity. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT01182792; URL: www.clinicaltrials.gov.

Right ventricular dysfunction in children and adolescents conceived by assisted reproductive technologies.

Assisted reproductive technologies (ART) predispose the offspring to vascular dysfunction, arterial hypertension, and hypoxic pulmonary hypertension. Recently, cardiac remodeling and dysfunction during fetal and early postnatal life have been reported in offspring of ART, but it is not known whether these cardiac alterations persist later in life and whether confounding factors contribute to this problem. We, therefore, assessed cardiac function and pulmonary artery pressure by echocardiography in 54 healthy children conceived by ART (mean age 11.5 ± 2.4 yr) and 54 age-matched (12.2 ± 2.3 yr) and sex-matched control children. Because ART is often associated with low birth weight and prematurity, two potential confounders associated with cardiac dysfunction, only singletons born with normal birth weight at term were studied. Moreover, because cardiac remodeling in infants conceived by ART was observed in utero, a situation associated with increased right heart load, we also assessed cardiac function during high-altitude exposure, a condition associated with hypoxic pulmonary hypertension-induced right ventricular overload. We found that, while at low altitude cardiac morphometry and function was not different between children conceived by ART and control children, under the stressful conditions of high-altitude-induced pressure overload and hypoxia, larger right ventricular end-diastolic area and diastolic dysfunction (evidenced by lower E-wave tissue Doppler velocity and A-wave tissue Doppler velocity of the lateral tricuspid annulus) were detectable in children and adolescents conceived by ART. In conclusion, right ventricular dysfunction persists in children and adolescents conceived by ART. These cardiac alterations appear to be related to ART per se rather than to low birth weight or prematurity.

Analysis of left ventricular function of the mouse heart during experimentally induced hyperthyroidism and recovery

Many of the clinical manifestations of hyperthyroidism are due to the ability of thyroid hormones to alter myocardial contractility and cardiovascular hemodynamics, leading to cardiovascular impairment. In contrast, recent studies highlight also the potential beneficial effects of thyroid hormone administration for clinical or preclinical treatment of different diseases such as atherosclerosis, obesity and diabetes or as a new therapeutic approach in demyelinating disorders. In these contexts and in the view of developing thyroid hormone-based therapeutic strategies, it is, however, important to analyze undesirable secondary effects on the heart. Animal models of experimentally induced hyperthyroidism therefore represent important tools for investigating and monitoring changes of cardiac function. In our present study we use high-field cardiac MRI to monitor and follow-up longitudinally the effects of prolonged thyroid hormone (triiodothyronine) administration focusing on murine left ventricular function. Using a 9.4 T small horizontal bore animal scanner, cinematographic MRI was used to analyze changes in ejection fraction, wall thickening, systolic index and fractional shortening. Cardiac MRI investigations were performed after sustained cycles of triiodothyronine administration and treatment arrest in adolescent (8 week old) and adult (24 week old) female C57Bl/6 N mice. Triiodothyronine supplementation of 3 weeks led to an impairment of cardiac performance with a decline in ejection fraction, wall thickening, systolic index and fractional shortening in both age groups but with a higher extent in the group of adolescent mice. However, after a hormonal treatment cessation of 3 weeks, only young mice are able to partly restore cardiac performance in contrast to adult mice lacking this recovery potential and therefore indicating a presence of chronically developed heart pathology.

Clipping techniques in cerebral aneurysm surgery

The history of cerebral aneurysm surgery owes a great tribute to the tenacity of pioneering neurosurgeons who designed and developed the clips used to close the aneurysms neck. However, until the beginning of the past century, surgery of complex and challenging aneurysms was impossible due to the lack of surgical microscope and commercially available sophisticated clips. The modern era of the spring clips began in the second half of last century. Until then, only malleable metal clips and other non-metallic materials were available for intracranial aneurysms. Indeed, the earliest clips were hazardous and difficult to handle. Several neurosurgeons put their effort in developing new clip models, based on their personal experience in the treatment of cerebral aneurysms. Finally, the introduction of the surgical microscope, together with the availability of more sophisticated clips, has allowed the treatment of complex and challenging aneurysms. However, today none of the new instruments or tools for surgical therapy of aneurysms could be used safely and effectively without keeping in mind the lessons on innovative surgical techniques provided by great neurovascular surgeons. Thanks to their legacy, we can now treat many types of aneurysms that had always been considered inoperable. In this article, we review the basic principles of surgical clipping and illustrate some more advanced techniques to be used for complex aneurysms.

Prevention of ischemic complications during aneurysm surgery

Ischemic complications during aneurysm surgery are a frequent cause of postoperative infarctions and new neurological deficits. In this article, we discuss imaging and neurophysiological tools that may help the surgeon to detect intraoperative ischemia. The strength of intraoperative digital subtraction angiography (DSA) is the full view of the arterial and venous vessel. DSA is the gold standard in complex and giant aneurysms, but due to certain disadvantages, it cannot be considered standard of care. Microvascular Doppler sonography is probably the fastest diagnostic tool and can quickly aid diagnosis of large vessel occlusions. Intraoperative indocyanine green videoangiography is the best tool to assess flow in perforating and larger arteries, as well as occlusion of the aneurysm sac. Intraoperative neurophysiological monitoring with somatosensory and motor evoked potentials indirectly measures blood flow by recording neuronal function. It covers all causes of intraoperative ischemia, provided that ischemia occurs in the brain areas under surveillance. However, every method has advantages and disadvantages. No single method is superior to the others in every aspect. Therefore, it is very important for the neurosurgeon to know the strengths and weaknesses of each tool in order to have them available, to know how to use them for each individual situation, and to be ready to apply them within the time window for reversible cerebral ischemia.

The unruptured intracranial aneurysm treatment score: a multidisciplinary consensus.

OBJECTIVE We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research. METHODS An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (vr*) (vr* = 0 indicating excellent agreement and vr* = 1 indicating poor agreement). RESULTS The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1-4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1-4.4) for panel members and 4.5 (95% CI 4.3-4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1-4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9-4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (vr*) for both cohorts was 0.026 (95% CI 0.019-0.033). CONCLUSIONS This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA.

Use of echocardiography reveals reestablishment of ventricular pumping efficiency and partial ventricular wall motion recovery upon ventricular cryoinjury in the zebrafish

AIMS While zebrafish embryos are amenable to in vivo imaging, allowing the study of morphogenetic processes during development, intravital imaging of adults is hampered by their small size and loss of transparency. The use of adult zebrafish as a vertebrate model of cardiac disease and regeneration is increasing at high speed. It is therefore of great importance to establish appropriate and robust methods to measure cardiac function parameters. METHODS AND RESULTS Here we describe the use of 2D-echocardiography to study the fractional volume shortening and segmental wall motion of the ventricle. Our data show that 2D-echocardiography can be used to evaluate cardiac injury and also to study recovery of cardiac function. Interestingly, our results show that while global systolic function recovered following cardiac cryoinjury, ventricular wall motion was only partially restored. CONCLUSION Cryoinjury leads to long-lasting impairment of cardiac contraction, partially mimicking the consequences of myocardial infarction in humans. Functional assessment of heart regeneration by echocardiography allows a deeper understanding of the mechanisms of cardiac regeneration and has the advantage of being easily transferable to other cardiovascular zebrafish disease models.

Propofol sedation administered by cardiologists for patients undergoing catheter ablation for ventricular tachycardia

AIMS Propofol sedation has been shown to be safe for atrial fibrillation ablation and internal cardioverter-defibrillator implantation but its use for catheter ablation (CA) of ventricular tachycardia (VT) has yet to be evaluated. Here, we tested the hypothesis that VT ablation can be performed using propofol sedation administered by trained nurses under a cardiologist's supervision. METHODS AND RESULTS Data of 205 procedures (157 patients, 1.3 procedures/patient) undergoing CA for sustained VT under propofol sedation were analysed. The primary endpoint was change of sedation and/or discontinuation of propofol sedation due to side effects and/or haemodynamic instability. Propofol cessation was necessary in 24 of 205 procedures. These procedures (Group A; n = 24, 11.7%) were compared with those with continued propofol sedation (Group B; n = 181, 88.3%). Propofol sedation was discontinued due to hypotension (n = 22; 10.7%), insufficient oxygenation (n = 1, 0.5%), or hypersalivation (n = 1, 0.5%). Procedures in Group A were significantly longer (210 [180-260] vs. 180 [125-220] min, P = 0.005), had a lower per hour propofol rate (3.0 ± 1.2 vs. 3.8 ± 1.2 mg/kg of body weight/h, P = 0.004), and higher cumulative dose of fentanyl administered (0.15 [0.13-0.25] vs. 0.1 [0.05-0.13] mg, P < 0.001), compared with patients in Group B. Five (2.4%) adverse events occurred. CONCLUSION Sedation using propofol can be safely performed for VT ablation under the supervision of cardiologists. Close haemodynamic monitoring is required, especially in elderly patients and during lengthy procedures, which carrying a higher risk for systolic blood pressure decline.

Epicardial phrenic nerve displacement during catheter ablation of atrial and ventricular arrhythmias: procedural experience and outcomes.

BACKGROUND Arrhythmia origin in close proximity to the phrenic nerve (PN) can hinder successful catheter ablation. We describe our approach with epicardial PN displacement in such instances. METHODS AND RESULTS PN displacement via percutaneous pericardial access was attempted in 13 patients (age 49±16 years, 9 females) with either atrial tachycardia (6 patients) or atrial fibrillation triggered from a superior vena cava focus (1 patient) adjacent to the right PN or epicardial ventricular tachycardia origin adjacent to the left PN (6 patients). An epicardially placed steerable sheath/4 mm-catheter combination (5 patients) or a vascular or an esophageal balloon (8 patients) was ultimately successful. Balloon placement was often difficult requiring manipulation via a steerable sheath. In 2 ventricular tachycardia cases, absence of PN capture was achieved only once the balloon was directly over the ablation catheter. In 3 atrial tachycardia patients, PN displacement was not possible with a balloon; however, a steerable sheath/catheter combination was ultimately successful. PN displacement allowed acute abolishment of all targeted arrhythmias. No PN injury occurred acutely or in follow up. Two patients developed acute complications (pleuro-pericardial fistula 1 and pericardial bleeding 1). Survival free of target arrhythmia was achieved in all atrial tachycardia patients; however, a nontargeted ventricular tachycardia recurred in 1 patient at a median of 13 months' follow up. CONCLUSIONS Arrhythmias originating in close proximity to the PN can be targeted successfully with PN displacement with an epicardially placed steerable sheath/catheter combination, or balloon, but this strategy can be difficult to implement. Better tools for phrenic nerve protection are desirable.