Mechano-electrical interactions and heterogeneities in wild-type and drug-induced long QT syndrome rabbits.

Electromechanical reciprocity - comprising electro-mechanical (EMC) and mechano-electric coupling (MEC) - provides cardiac adaptation to changing physiological demands. Understanding electromechanical reciprocity and its impact on function and heterogeneity in pathological conditions - such as (drug-induced) acquired long QT syndrome (aLQTS) - might lead to novel insights in arrhythmogenesis. Our aim is to investigate how electrical changes impact on mechanical function (EMC) and vice versa (MEC) under physiological conditions and in aLQTS.

A computational model of rabbit geometry and ECG: Optimizing ventricular activation sequence and APD distribution.

Computational modeling of electrophysiological properties of the rabbit heart is a commonly used way to enhance and/or complement findings from classic lab work on single cell or tissue levels. Yet, thus far, there was no possibility to extend the scope to include the resulting body surface potentials as a way of validation or to investigate the effect of certain pathologies. Based on CT imaging, we developed the first openly available computational geometrical model not only of the whole heart but also the complete torso of the rabbit.

Analysis of accelerated 4D flow MRI in the murine aorta by radial acquisition and compressed sensing reconstruction.

Preclinical 4D flow MRI remains challenging and is restricted for parallel imaging acceleration due to the limited number of available receive channels. A radial acquisition with combined parallel imaging and temporal compressed sensing reconstruction was implemented to achieve accelerated preclinical 4D flow MRI. In order to increase the accuracy of the measured velocities, a quantitative evaluation of different temporal regularization weights for the compressed sensing reconstruction based on velocity instead of magnitude data is performed.

Molecular magnetic resonance imaging of activated platelets allows noninvasive detection of early myocarditis in mice.

MRI sensitivity for diagnosis and localization of early myocarditis is limited, although it is of central clinical interest. The aim of this project was to test a contrast agent targeting activated platelets consisting of microparticles of iron oxide (MPIO) conjugated to a single-chain antibody directed against ligand-induced binding sites (LIBS) of activated glycoprotein IIb/IIIa (= LIBS-MPIO). Myocarditis was induced by subcutaneous injection of an emulsion of porcine cardiac myosin and complete Freund's adjuvant in mice.

Assessment of diastolic dysfunction: comparison of different cardiovascular magnetic resonance techniques.

Aims: Heart failure with preserved ejection fraction is still a diagnostic and therapeutic challenge, and accurate non-invasive diagnosis of left ventricular (LV) diastolic dysfunction (DD) remains difficult. The current study aimed at identifying the most informative cardiovascular magnetic resonance (CMR) parameters for the assessment of LVDD.

Methods And Results: We prospectively included 50 patients and classified them into three groups: with DD (DD+, n = 15), without (DD-, n = 26), and uncertain (DD±, n = 9).

Transgenic short-QT syndrome 1 rabbits mimic the human disease phenotype with QT/action potential duration shortening in the atria and ventricles and increased ventricular tachycardia/ventricular fibrillation inducibility.

Aims: Short-QT syndrome 1 (SQT1) is an inherited channelopathy with accelerated repolarization due to gain-of-function in HERG/IKr. Patients develop atrial fibrillation, ventricular tachycardia (VT), and sudden cardiac death with pronounced inter-individual variability in phenotype. We generated and characterized transgenic SQT1 rabbits and investigated electrical remodelling.

Electro-mechanical (dys-)function in long QT syndrome type 1.

Background: Prolonged repolarization is the hallmark of long QT syndrome (LQTS), which is associated with subclinical mechanical dysfunction. We aimed at elucidating mechanical cardiac function in LQTS type 1 (loss of I) and its modification upon further prolongation of the action potential (AP) by I-blockade (E-4031).

Methods: Transgenic LQT1 and wild type (WT) rabbits (n = 12/10) were subjected to tissue phase mapping MRI, ECG, and epicardial AP recording.

Coronary magnetic resonance imaging after routine implantation of bioresorbable vascular scaffolds allows non-invasive evaluation of vascular patency.

Background: Evaluation of recurrent angina after percutaneous coronary interventions is challenging. Since bioresorbable vascular scaffolds (BVS) cause no artefacts in magnetic resonance imaging (MRI) due to their polylactate-based backbone, evaluation of vascular patency by MRI might allow for non-invasive assessment and triage of patients with suspected BVS failure.

Methods: Patients with polylactate-based ABSORB-BVS in proximal coronary segments were examined with 3 Tesla MRI directly (baseline) and one year after implantation.

Segmental biventricular analysis of myocardial function using high temporal and spatial resolution tissue phase mapping.

Objective: Myocardial dysfunction of the right ventricle (RV) is an important indicator of RV diseases, e.g. RV infarction or pulmonary hypertension.

Preclinical 4D-flow magnetic resonance phase contrast imaging of the murine aortic arch.

Purpose: Cardiovascular diseases remain the number one death cause worldwide. Preclinical 4D flow phase contrast magnetic resonance imaging can provide substantial insights in the analysis of aortic pathophysiologies in various animal models. These insights may allow a better understanding of pathophysiologies, therapy monitoring, and can possibly be translated to humans.

Left ventricular regional myocardial motion and twist function in repaired tetralogy of Fallot evaluated by magnetic resonance tissue phase mapping.

Objectives: We aimed to characterise regional myocardial motion and twist function in the left ventricles (LV) in patients with repaired tetralogy of Fallot (rTOF) and preserved LV global function.

Methods: We recruited 47 rTOF patients and 38 age-matched normal volunteers. Tissue phase mapping (TPM) was performed for evaluating the LV myocardial velocity in longitudinal, radial, and circumferential (Vz, Vr, and VØ) directions in basal, middle, and apical slices.

Interregional electro-mechanical heterogeneity in the rabbit myocardium.

Background: Increased electrical heterogeneity has been causatively linked to arrhythmic disorders, yet the knowledge about physiological heterogeneity remains incomplete. This study investigates regional electro-mechanical heterogeneities in rabbits, one of the key animal models for arrhythmic disorders.

Methods And Findings: 7 wild-type rabbits were examined by phase-contrast magnetic resonance imaging in vivo to assess cardiac wall movement velocities.

Phase-contrast magnet resonance imaging reveals regional, transmural, and base-to-apex dispersion of mechanical dysfunction in patients with long QT syndrome.

Background: Regional dispersion of prolonged repolarization is a hallmark of long QT syndrome (LQTS). We have also revealed regional heterogeneities in mechanical dysfunction in transgenic rabbit models of LQTS.

Objective: In this clinical pilot study, we investigated whether patients with LQTS exhibit dispersion of mechanical/diastolic dysfunction.

Myocardial dysfunction in patients with aortic stenosis and hypertensive heart disease assessed by MR tissue phase mapping.

Purpose: To identify abnormalities of myocardial velocities in patients with left ventricular pressure overload using magnetic resonance tissue phase mapping (TPM).

Material And Methods: Thirty-three patients (nine with hypertensive heart disease [HYP], 24 with aortic stenosis [AS]) and 41 healthy controls were enrolled. To assess left ventricular motion, a basal, midventricular, and apical slice were acquired using three-directional velocity-encoded phase-contrast MR with a 3T system.

In vitro study to simulate the intracardiac magnetohydrodynamic effect.

Purpose: Blood flow causes induced voltages via the magnetohydrodynamic (MHD) effect distorting electrograms (EGMs) made during magnetic resonance imaging. To investigate the MHD effect in this context MHD voltages occurring inside the human heart were simulated in an in vitro model system inside a 1.5 T MR system.

Dual-contrast molecular imaging allows noninvasive characterization of myocardial ischemia/reperfusion injury after coronary vessel occlusion in mice by magnetic resonance imaging.

Background: Inflammation and myocardial necrosis play important roles in ischemia/reperfusion injury after coronary artery occlusion and recanalization. The detection of inflammatory activity and the extent of myocardial necrosis itself are of great clinical and prognostic interest. We developed a dual, noninvasive imaging approach using molecular magnetic resonance imaging in an in vivo mouse model of myocardial ischemia and reperfusion.

Cold ischaemic time and time after transplantation alter segmental myocardial velocities after heart transplantation.

Objectives: The aim of this study was to investigate changes in segmental, three-directional left ventricular (LV) velocities in patients after heart transplantation (Tx).

Methods: Magnetic resonance tissue phase mapping was used to assess myocardial velocities in patients after Tx (n = 27) with normal LV ejection fraction (63 ± 5%) and those without signs of rejection. Regional wall motion and dyssynchrony were analysed in relation to cold ischaemic time (150 ± 57 min, median = 154 min), age of the donor heart (35 ± 13 years, median = 29 years), time after transplantation (32 ± 26 months, median = 31 months) and global LV morphology and function.

Spatial correlation of action potential duration and diastolic dysfunction in transgenic and drug-induced LQT2 rabbits.

Background: Enhanced dispersion of action potential duration (APD) is a major contributor to long QT syndrome (LQTS)-related arrhythmias.

Objective: To investigate spatial correlations of regional heterogeneities in cardiac repolarization and mechanical function in LQTS.

Methods: Female transgenic LQTS type 2 (LQT2; n = 11) and wild-type littermate control (LMC) rabbits (n = 9 without E4031 and n = 10 with E4031) were subjected to phase contrast magnetic resonance imaging to assess regional myocardial velocities.

A quantitative comparison of regional myocardial motion in mice, rabbits and humans using in-vivo phase contrast CMR.

Background: Genetically manipulated animals like mice or rabbits play an important role in the exploration of human cardiovascular diseases. It is therefore important to identify animal models that closely mimic physiological and pathological human cardiac function.

Methods: In-vivo phase contrast cardiovascular magnetic resonance (CMR) was used to measure regional three-directional left ventricular myocardial motion with high temporal resolution in mice (N=18), rabbits (N=8), and humans (N=20).