Clinical implementation of a fully automated quantitative perfusion cardiovascular magnetic resonance imaging workflow with a simplified dual-bolus contrast administration scheme.

This study clinically implemented a ready-to-use quantitative perfusion (QP) cardiovascular magnetic resonance (QP CMR) workflow, encompassing a simplified dual-bolus gadolinium-based contrast agent (GBCA) administration scheme and fully automated QP image post-processing. Twenty-five patients with suspected obstructive coronary artery disease (CAD) underwent both adenosine stress perfusion CMR and an invasive coronary angiography or coronary computed tomography angiography. The dual-bolus protocol consisted of a pre-bolus (0.0075 mmol/kg GBCA at 0.5 mmol/ml concentration + 20 ml saline) and a main bolus (0.075 mmol/kg GBCA at 0.5 mmol/ml concentration + 20 ml saline) at an infusion rate of 3 ml/s. The arterial input function curves showed excellent quality. Stress MBF ≤ 1.84 ml/g/min accurately detected obstructive CAD (area under the curve 0.79; 95% Confidence Interval: 0.66 to 0.89). Combined visual assessment of color pixel QP maps and conventional perfusion images yielded a diagnostic accuracy of 84%, sensitivity of 70% and specificity of 93%. The proposed easy-to-use dual-bolus QP CMR workflow provides good image quality and holds promise for high accuracy in diagnosis of obstructive CAD. Implementation of this approach has the potential to serve as an alternative to current methods thus increasing the accessibility to offer high-quality QP CMR imaging by a wide range of CMR laboratories.

Reduced Microvascular Blood Volume as a Driver of Coronary Microvascular Disease in Patients With Non-obstructive Coronary Artery Disease: Rationale and Design of the MICORDIS Study.

Background: Ischemia with non-obstructive coronary arteries (INOCA) is part of the ischemic heart disease spectrum, and is particularly observed in women. INOCA has various mechanisms, such as coronary vasospasm and coronary microvascular dysfunction (CMD). A decreased coronary flow reserve (CFR) and-or increased myocardial resistance (MR) are commonly used to diagnose CMD. However, CFR and MR do not describe all pathophysiological mechanisms underlying CMD. Increased myocardial oxygen consumption (MVO2) normally increases myocardial blood volume (MBV), independently from myocardial blood flow (MBF). In addition insulin enhances MBV in healthy skeletal muscle, and this effect is impaired in INOCA-related conditions such as diabetes and obesity. Therefore, we propose that MBV is reduced in INOCA patients. Aim: To assess whether myocardial blood volume (MBV) is decreased in INOCA patients, at baseline, during hyperinsulinemia and during stress. Design: The MICORDIS-study is a single-center observational cross-sectional cohort study (identifier NTR7515). The primary outcome is MBV, compared between INOCA patients and matched healthy controls. The patient group will undergo coronary function testing using a Doppler guidewire, intracoronary adenosine and acetylcholine to measure CFR and coronary vasospasm. Both the patient- and the control group will undergo myocardial contrast echocardiography (MCE) to determine MBV at baseline, during hyperinsulinemia and during stress. Subsequently, cardiac magnetic resonance (CMR) will be evaluated as a new and noninvasive diagnostic tool for CMD in INOCA patients. Microvascular endothelial function is a determinant of MBV and will be evaluated by non-invasive microvascular function testing using EndoPAT and by measuring NO production in circulating endothelial cells (ECFCs).

Variable cardiac myosin binding protein-C expression in the myofilaments due to MYBPC3 mutations in hypertrophic cardiomyopathy.

BACKGROUND: Mutations in MYBPC3 are the most common cause of hypertrophic cardiomyopathy (HCM). These mutations produce dysfunctional protein that is quickly degraded and not incorporated in the myofilaments. Most patients are heterozygous and allelic expression differs between cells. We hypothesized that this would lead to cell-to-cell variation in cardiac myosin binding protein-C (cMyBP-C, encoded by MYBPC3 gene) protein levels. METHODS: Twelve HCM patients were included (six had no sarcomere mutations (HCMsmn) and served as the control group and six harbored mutations in the MYBPC3 gene (MYBPC3mut). Western blot and RNA sequencing analysis of cardiac tissue lysates were performed to detect overall cMyBP-C protein and mRNA levels. Cellular expression of cMyBP-C and α-actin was obtained by immunofluorescence staining. Quantification of cell-to-cell variation of cMyBP-C expression between cardiomyocytes was measured by determining the ratio of cMyBP-C:α-actin stained area of each cell. RESULTS: Protein and mRNA analysis revealed significantly reduced cMyBP-C levels in MYBPC3mut patients compared with HCMsmn patients (0.73 ±â€¯0.09 vs. 1.0 ±â€¯0.15, p < .05; 162.3 ±â€¯16.4 vs. 326.2 ±â€¯41.9 RPKM, p = .002), without any sign of truncated proteins. Immunofluorescence staining of individual cardiomyocytes in HCMsmn patients demonstrated homogenous and equal cMyBP-C:α-actin staining ratio. In contrast, MYBPC3mut patients demonstrated inhomogeneous staining patterns with a large intercellular variability per patient. Coefficient of variance for cMyBP-C/α-actin staining for each patient showed a significant difference between both groups (17.30 ±â€¯4.08 vs. 5.18 ±â€¯0.65% in MYBPC3mut vs. HCMsmn, p = .02). CONCLUSION: This is the first study to demonstrate intercellular variation of myofilament cMyBP-C protein expression within the myocardium from HCM patients with heterozygous MYBPC3 mutations.

Integrated whole-heart computational workflow for inverse potential mapping and personalized simulations.

BACKGROUND: Integration of whole-heart activation simulations and inverse potential mapping (IPM) could benefit the guidance and planning of electrophysiological procedures. Routine clinical application requires a fast and adaptable workflow. These requirements limit clinical translation of existing simulation models. This study proposes a comprehensive finite element model (FEM) based whole-heart computational workflow suitable for IPM and simulations. METHODS: Three volunteers and eight patients with premature ventricular contractions underwent body surface potential (BSP) acquisition followed by a cardiac MRI (CMR) scan. The cardiac volumes were segmented from the CMR images using custom written software. The feasibility to integrate tissue-characteristics was assessed by generating meshes with virtual edema and scar. Isochronal activation maps were constructed by identifying the fastest route through the cardiac volume using the Möller-Trumbore and Floyd-Warshall algorithms. IPM's were reconstructed from the BSP's. RESULTS: Whole-heart computational meshes were generated within seconds. The first point of atrial activation on IPM was located near the crista terminalis of the superior vena cave into the right atrium. The IPM demonstrated the ventricular epicardial breakthrough at the attachment of the moderator band with the right ventricular free wall. Simulations of sinus rhythm were successfully performed. The conduction through the virtual edema and scar meshes demonstrated delayed activation or a complete conductional block respectively. CONCLUSION: The proposed FEM based whole-heart computational workflow offers an integrated platform for cardiac electrical assessment using simulations and IPM. This workflow can incorporate patient-specific electrical parameters, perform whole-heart cardiac activation simulations and accurately reconstruct cardiac activation sequences from BSP's.

Cardiac magnetic resonance imaging: artefacts for clinicians.

In recent years, the clinical importance of cardiac magnetic resonance (CMR) imaging has increased dramatically. As a consequence, more clinicians need to become familiar with this imaging modality, including its technical challenges. MR images are obtained through a physical process of proton excitation and the reception of resonating signals. Besides these physical principles, the motion of the heart and diaphragm, together with the presence of fast flowing blood in the vicinity, pose challenges to the acquisition of high-quality diagnostic images and are an important cause of image artefacts. Artefacts may render images non-diagnostic and measurements unreliable, and most artefacts can only be corrected during the acquisition itself. Hence, timely and accurate recognition of the type of artefact is crucial. This paper provides a concise description of the CMR acquisition process and the underlying MR physics for clinical cardiologists and trainees. Frequently observed CMR artefacts are illustrated and possible adjustments to minimise or eliminate these artefacts are explained.

Multimodality imaging for patient evaluation and guidance of catheter ablation for atrial fibrillation - current status and future perspective.

Left atrial catheter ablation is an established non-pharmacological therapy for the treatment of atrial fibrillation. The importance of a noninvasive multimodality imaging approach is emphasized by the current guidelines for the various phases of the ablation work-up e.g. patient identification, therapy guidance and procedural evaluation. Advances in the capabilities of imaging modalities and the increasing cost of healthcare warrant a review of the multimodality approach. This review discusses the application of cardiac imaging for pulmonary vein and left atrial ablation divided into stages: pre-procedural stage (assessment of left atrial dimensions, left atrial appendage thrombus and pulmonary vein anatomy), peri-procedural stage (integration of anatomical and electrical information) and post-procedural stage (evaluation of efficacy by assessment of tissue properties). Each section is dedicated to one of the subtopics of a stage, allowing a thorough comparison to be made between the strengths and weaknesses of the different imaging modalities and the identification of one that exhibits the potential for a single technique approach.

MRI and cardiac implantable electronic devices; current status and required safety conditions.

Magnetic resonance imaging (MRI) has evolved into an essential diagnostic modality for the evaluation of all patient categories. This gain in popularity coincided with an increase in the number of implanted cardiac implantable electronic devices (CIEDs). Therefore, questions arose with regard to the MRI compatibility of these devices. Various investigators have reported the harmless performance of MRI in patients with conventional (non-MRI conditional) devices. The recently published European Society of Cardiology (ESC) guidelines on cardiac pacing and cardiac resynchronisation therapy (CRT) indicate that MRI can be safely performed in patients with an implanted pacemaker or ICD (MRI conditional or not), as long as strict safety conditions are met. This is a major modification of the former general opinion that patients with a pacemaker or ICD were not eligible to undergo MRI. This review paper attempts to elucidate the current situation for practising cardiologists by providing a clear overview of the potential life-threatening interactions and discuss safety measures to be taken prior to and during scanning. An overview of all available MRI conditional devices and their individual restrictions is given. In addition, an up-to-date safety protocol is provided that can be used to ensure patient safety before, during and after the scan. Key points • Historically, MRI examination of patients with a CIED has been considered hazardous. • Ongoing advances in technology and increasing usage of MRI in clinical practice have led to the introduction of MRI conditional CIEDs and to more lenient regulations on the examination of patients with non-conditional CIEDs. • MRI investigations can be performed safely in selected patients when adhering to a standardised up-to-date safety protocol.

New insights in LV torsion for the selection of cardiac resynchronisation therapy candidates.

Recent literature indicates that torsion of the left ventricle (LV) is a promising predictor for response to cardiac resynchronisation therapy (CRT). Among patients with severe heart failure, 45 to 75% of patients show rigid body rotation, where the base and apex rotate in the same direction, instead of normal, opposite rotation. The occurrence of this phenomenon seems to be a good indicator for response to CRT. From this review, it can be concluded that LV torsion might be a welcome addition to current selection criteria.

Magnetic resonance imaging in patients with a pacemaker system designed for the magnetic resonance environment.

BACKGROUND: Magnetic resonance imaging (MRI) of pacemaker patients is contraindicated due to documented potential risks to the patient from hazardous interactions between the MRI and pacemaker system. OBJECTIVE: The purpose of this prospective, randomized, controlled, worldwide clinical trial was to evaluate the safety and effectiveness of a pacemaker system designed for safe use in MRI for any bradycardia indicated patient. METHODS: Patients (n = 464) were randomized to undergo an MRI scan between 9 and 12 weeks postimplant (MRI group, n = 258) or not to undergo MRI (control group, n = 206) after successful implantation of the specially designed dual-chamber pacemaker and leads. Patients were monitored for arrhythmias, symptoms, and pacemaker system function during 14 nonclinically indicated relevant brain and lumbar MRI sequences. Sequences were performed at 1.5 T and included scans with high radiofrequency power deposition and/or high gradient dB/dt exposure. Clinical evaluation of the pacemaker system function occurred immediately before and after MRI, 1 week and 1 month post-MRI, and at corresponding times for the control group. Primary endpoints for safety analyzed the MRI procedure complication-free rate and for effectiveness compared capture and sensing performance between MRI and control groups. RESULTS: No MRI-related complications occurred during or after MRI, including sustained ventricular arrhythmias, pacemaker inhibition or output failures, electrical resets, or other pacemaker malfunctions. Pacing capture threshold and sensed electrogram amplitude changes were minimal and similar between study groups. CONCLUSION: This trial documented the ability of this pacemaker system to be exposed in a controlled fashion to MRI in a 1.5 T scanner without adverse impact on patient outcomes or pacemaker system function.

The role of cardiac magnetic resonance imaging in differentiating the underlying causes of left ventricular hypertrophy.

The onset of sudden cardiac death and large inter- and intra-familial clinical variability of hypertrophic cardiomyopathy pose an important clinical challenge. Cardiac magnetic resonance imaging is a high-resolution imaging modality that has become increasingly available in the past decade and has the unique possibility to demonstrate the presence of fibrosis or scar using late gadolinium enhancement imaging. As a result, the diagnostic and prognostic potential of cardiac magnetic resonance imaging has been extensively explored in acute and chronic ischaemic cardiomyopathy, as well as in several nonischaemic cardiomyopathies.This review aims to provide a critical overview of recently published studies on hypertrophic cardiomyopathy and discusses the role of cardiac magnetic resonance imaging in differentiating underlying causes of hypertrophic cardiomyopathy, such as familial hypertrophic cardiomyopathy, cardiac involvement in systemic disease and left ventricular hypertrophy due to endurance sports. Also, it demonstrates the use of cardiac magnetic resonance in risk stratification for the onset of sudden cardiac death, and early identification of asymptomatic family members of hypertrophic cardiomyopathy patients who are at risk for the development of hypertrophic cardiomyopathy. (Neth Heart J 2010;18:135-43.).

Cardiac PET-CT: advanced hybrid imaging for the detection of coronary artery disease.

Hybrid imaging of positron emission tomography (PET) together with computed tomography (CT) is rapidly emerging. In cardiology, this new advanced hybrid imaging modality allows quantification of cardiac perfusion in combination with assessment of coronary anatomy within a single scanning session of less than 45 minutes. The near-simultaneous anatomical evaluation of coronary arteries using CT and corresponding functional status using PET provides a wealth of complementary information in patients who are being evaluated for (suspected) coronary artery disease, and could help guide clinical patient management in a novel manner. Clinical experience gained with this recently introduced advanced hybrid imaging tool, however, is still limited and its implementation into daily clinical practice remains largely unchartered territory. This review discusses principles of perfusion PET, its diagnostic accuracy, and potential clinical applications of cardiac PET-CT in patients with ischaemic heart disease. (Neth Heart J 2010;18:90-8.).

Magnetic resonance imaging, pacemakers and implantable cardioverter-defibrillators: current situation and clinical perspective.

New developments and expanding indications have resulted in a significant increase in the number of patients with pacemakers and internal cardioverterdefibrillators (ICDs). Because of its unique capabilities, magnetic resonance imaging (MRI) has become one of the most important imaging modalities for evaluation of the central nervous system, tumours, musculoskeletal disorders and some cardiovascular diseases. As a consequence of these developments, an increasing number of patients with implanted devices meet the standard indications for MRI examination. Due to the presence of potential life-threatening risks and interactions, however, pacemakers and ICDs are currently not approved by the Food and Drug Administration (FDA) for use in an MRI scanner. Despite these limitations and restrictions, a limited but still growing number of studies reporting on the effects and safety issues of MRI and implanted devices have been published. Because physicians will be increasingly confronted with the issue of MRI in patients with implanted devices, this overview is given. The effects of MRI on an implanted pacemaker and/or ICDs and vice versa are described and, based on the current literature, a strategy for safe performance of MRI in these patients is proposed. (Neth Heart J 2010;18:31-7.).

Potential of [11C]acetate for measuring myocardial blood flow: Studies in normal subjects and patients with hypertrophic cardiomyopathy.

BACKGROUND: Measuring the rate of clearance of carbon-11 labelled acetate from myocardium using positron emission tomography (PET) is an accepted technique for noninvasively assessing myocardial oxygen consumption. Initial myocardial uptake of [(11)C]acetate, however, is related to myocardial blood flow (MBF) and several tracer kinetic models for quantifying MBF using [(11)C]acetate have been proposed. The objective of this study was to assess these models. METHODS: Eighteen healthy subjects and 18 patients with hypertrophic cardiomyopathy (HCM) were studied under baseline conditions with [(11)C]acetate and [(15)O]water. Four previously reported methods, including single- and multi-tissue compartment models, were used to calculate MBF from the measured [(11)C]acetate rate of influx K (1) and the (previously) reported relationship between K (1) and MBF. These MBF values were then compared with those derived from corresponding [(15)O]water studies. RESULTS: For all models, correlations between [(11)C]acetate and [(15)O]water-derived MBF ranged from .67 to .86 (all P < .005) in the control group and from .73 to .85 (all P < .001) in the HCM group. Two out of four models systematically underestimated perfusion with [(11)C]acetate, whilst the third model resulted in an overestimation. The fourth model, based on a simple single tissue compartment model with spillover, partial volume and recirculating metabolite corrections, resulted in a regression equation with a slope of near unity and an Y-intercept of almost zero (controls, K(1) = .74[MBF] + .09, r = .86, SEE = .13, P < .001 and HCM, K(1) = .89[MBF] + .03, r = .85, SEE = .12, P < .001). CONCLUSION: [(11)C]acetate enables quantification of MBF in fairly good agreement with actual MBF in both healthy individuals and patients with HCM. A single tissue compartment model with standardized correction for recirculating metabolites and with corrections for partial volume and spillover provided the best results.

Quantification of global left ventricular function: comparison of multidetector computed tomography and magnetic resonance imaging. a meta-analysis and review of the current literature.

Cardiac morbidity and mortality are closely related to cardiac volumes and global left ventricular (LV) function, expressed as left ventricular ejection fraction. Accurate assessment of these parameters is required for the prediction of prognosis in individual patients as well as in entire cohorts. The current standard of reference for left ventricular function is analysis by short-axis magnetic resonance imaging. In recent years, major extensive technological improvements have been achieved in computed tomography. The most marked development has been the introduction of the multidetector CT (MDCT), which has significantly improved temporal and spatial resolutions. In order to assess the current status of MDCT for analysis of LV function, the current available literature on this subject was reviewed. The data presented in this review indicate that the global left ventricular functional parameters measured by contemporary multi-detector row systems combined with adequate reconstruction algorithms and post-processing tools show a narrow diagnostic window and are interchangeable with those obtained by MRI.

Regional timing of myocardial shortening is related to prestretch from atrial contraction: assessment by high temporal resolution MRI tagging in humans.

Earlier studies have shown substantial nonuniformity in normal left ventricular (LV) myocardial function concerning both the degree of shortening and timing of shortening. We hypothesized that nonuniform LV function may be related to nonuniform prestretch induced by atrial contraction. Eleven healthy human subjects were studied using MRI myocardial tagging and strain analysis. The amount of circumferential prestretch was assessed in 30 LV segments. Prestretch was defined as the difference in strain between end diastole (at ECG R wave) and diastasis. Furthermore, both the degree of shortening (quantified as peak circumferential shortening, peak systolic shortening rate, and amount of postsystolic shortening) and timing of shortening (quantified as the onset time of shortening and time to peak shortening) were assessed. LV prestretch was found to be nonuniform, with the highest values in the lateral wall. The amount of segmental prestretch correlated significantly with peak shortening (r = 0.79), peak shortening rate (r = 0.50), amount of postsystolic shortening (r = 0.67), onset time of shortening (r = -0.57), and time to peak shortening (r = 0.71) (P < 0.001 for each of these relations). These relations may be explained by regional differences in wall stress or by a regional Frank-Starling effect. The correlation between timing of shortening and prestretch demonstrates that mechanical timing is not determined by electrical phenomena alone. In conclusion, regional variation in LV function correlates with the nonuniform prestretch from atrial contraction.

Timing of cardiac contraction in humans mapped by high-temporal-resolution MRI tagging: early onset and late peak of shortening in lateral wall.

Mechanical asynchrony is an important parameter in predicting the response to cardiac resynchronization therapy, but detailed knowledge of cardiac contraction timing in healthy persons is scarce. In this work, timing of cardiac contraction was mapped in 17 healthy subjects with high-temporal-resolution (14 ms) MRI myocardial tagging and strain analysis. Both the onset time of circumferential shortening (T(onset)) in early systole and the time of peak circumferential shortening (T(peak)) at end systole were determined. The onset of shortening width (time needed for 20-90% of the left ventricle to start shortening) was small (35 +/- 9 ms). A distinct spatial pattern for T(onset) was found, with earliest onset in the lateral wall and latest onset in the septum (P = 0.001). Compared with T(onset), T(peak) had a larger width (121 +/- 22 ms) and an opposite spatial pattern, with peak shortening occurring earlier in the septum than in the lateral wall (P < 0.001). Postsystolic shortening (T(peak) later than aortic valve closure; P < 0.05) was observed in 13 of the 30 cardiac segments, mainly in the lateral and basal segments. Shortening in these segments continued 58 +/- 14 ms after aortic valve closure, during which circumferential shortening increased from 16.9 +/- 1.2% to 20.0 +/- 1.5%. Maps of the timing of contraction in normal subjects may serve as a reference in detecting mechanical asynchrony due to intraventricular conduction defects or ischemia.