Ciliary regulation of endothelial response to shear stress : consequences for Tgf-beta signaling and endothelial-to-mesenchymal transition

In het proefschrift staat de respons van endotheelcellen (celpopulatie aan de binnenzijde van het hart en de bloedvaten) op verschillende hemodynamische condities centraal. In het bijzonder de bijdrage van bloedstroom ge_nduceerde endotheelcel differentiatie aan embryonale hartklep en -septum (tussenschot) ontwikkeling nader onderzocht. In de endotheelcellen is de rol van primaire cilia (haar-achtige sensors aan het celoppervlak) in de interactie tussen specifieke moleculaire signaleringcascades die betrokken zijn bij de aanleg van hartkleppen bestudeerd. Een abnormale signalering door endotheelcellen in het hart kan bijdragen aan het ontstaan van hartklep- en septum afwijkingen. Deze aangeboren hartafwijkingen hebben een belangrijk plek in de kliniek en kunnen levensbedreigend zijn.Dutch Heart Foundation and J.E.Jurriaanse Stichting.UBL - phd migration 201

Early detection of fluid retention in patients with advanced heart failure: a review of a novel multisensory algorithm, HeartLogicTM

Heart failure (HF) hospitalisations due to decompensation are associated with shorter lifeexpectancy and lower quality of life. These hospitalisations pose a significant burden on the patients,doctors and healthcare resources. Early detection of an upcoming episode of decompensationmay facilitate timely optimisation of the ambulatory medical treatment and thereby prevent heartfailure-related hospitalisations. The HeartLogicTM algorithm combines data from five sensors ofcardiac implantable electronic devices into a cumulative index value. It has been developed for earlydetection of fluid retention in heart failure patients. This review aims to provide an overview of thecurrent literature and experience with the HeartLogicTM algorithm, illustrate how the index can beimplemented in daily clinical practice and discuss ongoing studies and potential future developmentsof interest.Cardiolog

Fusion cardiac resynchronization therapy in an left ventricular assist device patient from two devices and crossing leads: a case report

Background Cardiac implanted electronic devices (CIED) have significantly improved the survival and quality of life in heart failure patients. Although implantable cardioverter-defibrillators (ICD) and cardiac resynchronization therapy (CRT) have a major role in patients with moderate to severe heart failure symptoms, the role of these devices in patients with a left ventricular assist device (LVAD) is not yet well defined. The burden of CIED-related procedures in patients with an LVAD is high. The price of lead malfunctions and pocket complications requires creative approaches to tackle CIED-related issues in this patient population.Case summary Here, we describe the clinical course of a 67-year-old ventricular pacing dependent LVAD patient with an ICD indication based on recurrent monomorphic ventricular tachycardias and a CRT indication due to previous deterioration of (right-sided) heart failure in the absence of biventricular pacing. We were confronted with impending right ventricular lead failure and bilateral venous access problems due to chronic subclavian vein occlusion in a patient with a total of five transvenous leads, therapeutic anticoagulation, and pronounced thoracic collaterals. We sought for a creative solution to be able to deliver effective biventricular fusion pacing with the existing leads from two contralateral pulse generators resulting in biventricular fusion pacing. This provided the solution to deliver effective CRT.Discussion This case illustrates the complexity of care and CIED-related decision-making in pacing dependent LVAD patients, in particularly those with an ICD and CRT indication.Cardiolog

Failing systemic right ventricle in a patient with dextrocardia and complex congenitally corrected transposition of the great arteries: a case report of successful transvenous cardiac resynchronization therapy

Background Patients with congenitally corrected transposition of the great arteries (ccTGA) are prone to the development of advanced atrio-ventricular block requiring chronic ventricular pacing. The morphological right ventricle (RV) often develops systolic dysfunction as it is unable to withstand the chronic pressure overload it is exposed to when supporting the systemic circulation.Case summary A 56-year-old woman with dextrocardia and complex ccTGA with a history of dual-chamber implantable cardioverter-defibrillator (DDD-ICD, high degree atrio-ventricular-block and syncopal ventricular tachycardia), presented with progressive heart failure and symptomatic atrial arrhythmias. She underwent a successful ablation and concomitant invasive haemodynamic evaluation of potential alternative/biventricular pacing modalities. During biventricular pacing, the QRS narrowed and the systemic RV intraventricular pressure (Dp/Dt) increased with 30%. She underwent a successful transvenous upgrade to cardiac resynchronization therapy (CRT). The electrocardiogram post-implantation showed biventricular capture and patient showed subjective and objective clinical improvement.Discussion Systemic RV dysfunction in ccTGA can be aggravated by chronic pacing-induced dyssynchrony, contributing to progression of heart failure in this patient group. Transvenous CRT is feasible in ccTGA anatomy and may be pursued in order to improve or preserve the functional status of pacing-dependent ccTGA patients. Invasive haemodynamic contractility evaluation can help assess the potential benefit of CRT in patients with complex anatomy.Cardiolog

Leucyl-tRNA synthetase from Thermus thermophilus. Purification and some properties of the crystallizing enzyme

Leucyl-tRNA synthetase from Thermus thermophilus (LeuRSTT) was purified to homogeneity using a five-step purification procedure. The enzyme was characterized and crystallized. Molecular mass determinations of the native and denatured proteins indicate monomeric structure of LeuRSTT with the molecular mass of about 101 kDa. The protein obtained is remarkably thermostable and retains 97 % of its initial aminoacylation activity after 1 hour of incubation at 88 °C. Crystals of LeuRSTT were obtained from ammonium sulfate solution by the vapour diffusion techniques. The crystals quality was improved by crystallization from the precipitate.Лейцил-тРНК синтетаза из Thermus thermophilus (ЛейРСТТ) выделена в гомогенном состоянии с использованием пяти стадий очистки. Фермент охарактеризован и получены его кристаллы. Определена молекулярная масса нашивного и дена­турированного белка. Установлено, что ЛейРСТТ представ­ляет собой мономер с молекулярной массой 101 кДа. Получен­ный фермент обладает значительной термостабильностью и сохраняет 97 % аминоацилирующей активности после инкуба­ции в течение 1 ч при температуре 88 °С. Кристаллы ЛейРСТТ получены методом диффузии паров с использованием в качестве осадителя раствора сульфата аммонияЛейцил-тРНК синтетазу із Thermus thermophilus (ЛейРСТТ) виділено в гомогенному стані з використанням п'яти стадій очищення. Фермент охарактеризовано та отримано його кристали. Визначено молекулярну масу нативного і денатуро­ваного білка. Встановлено, що ЛейРСТТ являє собою мономер з молекулярною масою 101 кДа. Отриманому ферментові притаманна значна термостабільність і він зберігає 97 % аміноацилюючої активності після інкубації протягом 1 год при температурі 88 ° С Кристали ЛейРСТТ одержано методом дифузії парів із використанням як осаджувана розчину сульфату амонію

Computed tomography derived coronary triangulated orifice area-deduction of a new parameter for follow-up after surgical correction of anomalous aortic origin of coronary arteries and call for validation

Introduction: Anomalous aortic origin of a coronary artery (AAOCA) from the opposite sinus of Valsalva is a rare congenital abnormality. Computed tomography angiography (CTA) is primarily used as a diagnostic tool to evaluate the anatomy and identify potentially malignant AAOCA variants. Limited data is available on the role of CTA during postoperative follow-up. We aimed to develop an objective CTA derived parameter for diagnostic evaluation and follow-up after surgical correction of AAOCA and correlate the anatomical features to the postoperative outcome.Methods: All consecutive patients who underwent surgical repair of AAOCA from 2001 to 2018 and had pre and postoperative CTA imaging available were included. A retrospective analysis of the pre- and postoperative CTA and the outcomes was performed. The origin and course of the anomalous coronary artery and the ostial dimensions were evaluated and correlated with restenosis of operated coronary artery. To allow an accurate evaluation of the effective orifice area at diagnosis and after surgical repair we deduce and propose a new parameter-the coronary triangulated orifice area (CTOA).Results: Out of the 54 patients who underwent surgical treatment for AAOCA, 11 fulfilled the inclusion criteria. The median follow-up was 19 months [IQR 3;42]. The mean age at surgery was 41 +/- 16 years, with six patients (55%) being male. Postoperatively, the angle between the proximal coronary artery and the aortic wall increased from 20 +/- 5 degrees to 28 +/- 9 degrees (p < 0.01) and ostial diameter in the transversal plane increased from 4.1 +/- 2.5 mm to 6.2 +/- 2.7 mm (p < 0.01). The median CTOA increased significantly from 1.6 mm(2) [IQR 0.9;4.9] to 5.5 mm(2) [IQR 3;11.8] (p < 0.005). During follow-up, in three patients a restenosis of the operated coronary artery was suspected. In these patients, the CTOA only showed a limited postoperative increase of <= 1.4 mm(2).Conclusions: CTA can play an important role in the evaluation of the pre- and postoperative anatomy in AAOCA patients. CTOA may be of use in conjunction with the acute angle take-off and ostial diameter order to comprehensively evaluate the operated ostium after unroofing or patch angioplasty.Cardiolog

The potential of sodium-glucose cotransporter 2 inhibitors for the treatment of systemic right ventricular failure in adults with congenital heart disease

AimsGiven the compelling evidence on the effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the conventional heart failure population, SGLT2i deserve exploration in systemic right ventricular (sRV) failure. The initial experience with dapagliflozin in sRV failure patients is described, with a focus on tolerability and short-term effects on clinical outcomes.Methods and resultsTen patients (70% female, median age 50 years [46.5-52]) with symptomatic sRV failure who received dapagliflozin 10 mg per day on top of optimal medical therapy between 04-2021 and 01-2023 were included. Within 4 weeks, no significant changes in blood pressure, electrolytes, or serum glucose occurred. Creatinine and estimated glomerular filtration rate (eGFR) showed a slight decline (88 & PLUSMN; 17 to 97 & PLUSMN; 23 & mu;mol/L, p = 0.036, and 72 & PLUSMN; 14 vs. 66 & PLUSMN; 16 ml/min/1.73m(2), p = 0.020, respectively). At 6 months follow-up (n = 8), median NT-proBNP decreased significantly from 736.6 [589.3-1193.3] to 531.6 [400.8-1018] ng/L (p = 0.012). Creatinine and eGFR recovered to baseline levels. There were no significant changes in echocardiographic systolic sRV or left ventricular function. New York Heart Association class improved significantly in 4 out of 8 patients (p = 0.046), who also showed an improvement in the 6-minute walk test or bicycle exercise test performance. One female patient developed an uncomplicated urinary tract infection. No patients discontinued treatment.ConclusionDapagliflozin was well-tolerated in this small cohort of sRV failure patients. While the early results on the reduction of NT-proBNP and clinical outcome parameters are encouraging, large-scale prospective studies are warranted to thoroughly evaluate the effects of SGLT2i in the growing sRV failure population

The coronary arteries in adults after the arterial switch operation: a systematic review

Coronary artery status in adults long after the arterial switch operation (ASO) is unclear. We conducted a systematic review to provide an overview of coronary complications during adulthood and to evaluate the value of routine coronary imaging in adults after ASO, in light of current guidelines. Articles were screened for the inclusion of adult ASO patients and data on coronary complications and findings of coronary imaging were collected. A total of 993 adults were followed with a median available follow-up of only 2.0 years after reaching adulthood. Myocardial ischemia was suspected in 17/192 patients (8.9%). The number of coronary interventions was four (0.4%), and coronary death was reported in four (0.4%) patients. A lack of ischemia-related symptoms cannot be excluded because innervation studies indicated deficient cardiac innervation after ASO, although data is limited. Anatomical high-risk features found by routine coronary computed tomography (cCT) included stenosis (4%), acute angle (40%), kinking (24%) and inter-arterial course (11%). No coronary complications were reported during pregnancy (n = 45), although, remarkably, four (9%) patients developed heart failure. The 2020 European Society of Cardiology (ESC) guidelines state that routine screening for coronary pathologies is questionable. Based on current findings and in line with the 2018 American ACC/AHA guidelines a baseline assessment of the coronary arteries in all ASO adults seems justifiable. Thereafter, an individualized coronary follow-up strategy is advisable at least until significant duration of follow-up is available.Cardiolog

Asymmetry and heterogeneity: part and parcel in cardiac autonomic innervation and function

The cardiac autonomic nervous system (cANS) regulates cardiac adaptation to different demands. The heart is an asymmetrical organ, and in the selection of adequate treatment of cardiac diseases it may be relevant to take into account that the cANS also has sidedness as well as regional differences in anatomical, functional, and molecular characteristics. The left and right ventricles respond differently to adrenergic stimulation. Isoforms of nitric oxide synthase, which plays an important role in parasympathetic function, are also distributed asymmetrically across the heart. Treatment of cardiac disease heavily relies on affecting left-sided heart targets which are thought to apply to the right ventricle as well. Functional studies of the right ventricle have often been neglected. In addition, many principles have only been investigated in animals and not in humans. Anatomical and functional heterogeneity of the cANS in human tissue or subjects is highly valuable for understanding left- and right-sided cardiac pathology and for identifying novel treatment targets and modalities. Within this perspective, we aim to provide an overview and synthesis of anatomical and functional heterogeneity of the cANS in tissue or subjects, focusing on the human heart.Perioperative Medicine: Efficacy, Safety and Outcome (Anesthesiology/Intensive Care

The clinical spectrum of Kommerell's diverticulum in adults with a right-sided aortic arch: a case series and literature overview

Background: Kommerell's diverticulum is a rare vascular anomaly characterized as an outpouch at the onset of an aberrant subclavian artery. In the variant of a right-sided aortic arch, the trachea and esophagus are enclosed dorsally by the arch. In the configuration of an aberrant left subclavian artery, a Kommerell's diverticulum and persisting ductus arteriosus or ductal ligament enclose the lateral side, forming a vascular ring which may result in (symptomatic) esophageal or tracheal compression. Spontaneous rupture of an aneurysmatic Kommerell's diverticulum has also been reported. Due to the rarity of this condition and underreporting in the literature, the clinical implications of a Kommerell's diverticulum are not well defined. Case summary: We describe seven consecutive adult patients with a right-sided aortic arch and an aberrant course of the left subclavian artery (arteria lusoria), and a Kommerell's diverticulum, diagnosed in our tertiary hospital. One patient had severe symptoms related to the Kommerell's diverticulum and underwent surgical repair. In total, two of the patients experienced mild non-limiting dyspnea complaints and in four patients the Kommerell's diverticulum was incidentally documented on a computed tomography (CT) scan acquired for a different indication. The size of the Kommerell's diverticulum ranged from 19 x 21 mm to 30 x 29 mm. In the six patients that did not undergo surgery, a strategy of periodic follow-up with structural imaging was pursued. No significant growth of the Kommerell's diverticulum was observed and none of the patients experienced an acute aortic syndrome to date. Discussion: Kommerell's diverticulum in the setting of a right-sided aortic arch with an aberrant left subclavian artery is frequently associated with tracheal and esophageal compression and this may result in a varying range of symptoms. Guidelines on management of Kommerell's diverticulum are currently lacking. This case series and literature overview suggests that serial follow-up is warranted in adult patients with a Kommerell's diverticulum with small dimensions and no symptoms, however, that surgical intervention should be considered when patients become symptomatic or when the diameter exceeds 30 mm in the absence of symptoms.Cardiolog