Measuring myocardial extracellular volume of the right ventricle in patients with congenital heart disease.

The right ventricle´s (RV) characteristics-thin walls and trabeculation-make it challenging to evaluate extracellular volume (ECV). We aimed to assess the feasibility of RV ECV measurements in congenital heart disease (CHD), and to introduce a novel ECV analysis tool. Patients (n = 39) and healthy controls (n = 17) underwent cardiovascular magnetic resonance T1 mapping in midventricular short axis (SAX) and transverse orientation (TRANS). Regions of interest (ROIs) were evaluated with regard to image quality and maximum RV wall thickness per ROI in pixels. ECV from plane ROIs was compared with values obtained with a custom-made tool that derives the mean T1 values from a "line of interest" (LOI) centered in the RV wall. In CHD, average image quality was good (no artifacts in the RV, good contrast between blood/myocardium), and RV wall thickness was 1-2 pixels. RV ECV was not quantifiable in 4/39 patients due to insufficient contrast or wall thickness < 1 pixel. RV myocardium tended to be more clearly delineated in SAX than TRANS. ECV from ROIs and corresponding LOIs correlated strongly in both directions (SAX/TRANS: r = 0.97/0.87, p < 0.001, respectively). In conclusion, RV ECV can be assessed if image quality allows sufficient distinction between myocardium and blood, and RV wall thickness per ROI is ≥ 1 pixel. T1 maps in SAX are recommended for RV ECV analysis. LOI application simplifies RV ECV measurements.

Cardiac T1 mapping in congenital heart disease: bolus vs. infusion protocols for measurements of myocardial extracellular volume fraction.

Myocardial extracellular volume fraction (ECV) reflecting diffuse myocardial fibrosis can be measured with T1 mapping cardiovascular magnetic resonance (CMR) before and after the application of a gadolinium-based extracellular contrast agent. The equilibrium between blood and myocardium contrast concentration required for ECV measurements can be obtained with a primed contrast infusion (equilibrium contrast-CMR). We hypothesized that equilibrium can also be achieved with a single contrast bolus to accurately measure diffuse myocardial fibrosis in patients with congenital heart disease (CHD). Healthy controls (n = 17; median age 24.0 years) and patients with CHD (n = 19; 25.0 years) were prospectively enrolled. Using modified Look-Locker inversion recovery T1 mapping before, 15 min after bolus injection, and during constant infusion of gadolinium-DOTA, T1 values were obtained for blood pool and myocardium of the left ventricle (LV), the interventricular septum (IVS), and the right ventricle (RV) in a single midventricular plane in short axis or in transverse orientation. ECV of LV, IVS and RV by bolus-only and bolus-infusion correlated significantly in CHD patients (r = 0.94, 0.95, and 0.74; p < 0.01, respectively) and healthy controls (r = 0.96, 0.89, and 0.64; p < 0.05, respectively). Bland-Altman plots revealed no significant bias between the techniques for any of the analyzed regions. ECV of LV and RV myocardium measured by bolus-only T1 mapping agrees well with bolus-infusion measurements in patients with CHD. The use of a bolus-only approach facilitates the integration of ECV measurements into existing CMR imaging protocols, allowing for assessment of diffuse myocardial fibrosis in CHD in clinical routine.

Percutaneous pulmonary valve replacement using completely tissue-engineered off-the-shelf heart valves: six-month in vivo functionality and matrix remodelling in sheep.

AIMS: The objective was to implant a stented decellularised tissue-engineered heart valve (sdTEHV) percutaneously in an animal model, to assess its in vivo functionality and to examine the repopulation and remodelling of the valvular matrix by the recipient's autologous cells. METHODS AND RESULTS: Prototypes of sdTEHV were cultured in vitro, decellularised and percutaneously implanted into the pulmonary position in 15 sheep. Functionality was assessed monthly by intracardiac echocardiography (ICE). Valves were explanted after eight, 16 or 24 weeks and analysed macroscopically, histologically and by electron microscopy. Implantation was successful in all animals. Valves showed normal pressure gradients throughout the study. Due to a suboptimal design with small coaptation area, stent ovality led to immediate regurgitation which continuously increased during follow-up. Analyses revealed complete endothelialisation and rapid cellular repopulation and remodelling of the entire matrix. Valves were free from endocarditis, calcification and graft rejection. CONCLUSIONS: sdTEHV can be safely implanted percutaneously. The fast autologous recellularisation and the extensive matrix remodelling demonstrate the valve's potential as a next-generation percutaneous prosthesis with the capacity for tissue self-maintenance and longevity. Regurgitation may be prevented by valve design optimisation.

Myocardial T1 maps reflect histological findings in acute and chronic stages of myocarditis in a rat model.

BACKGROUND: Cardiovascular magnetic resonance offers both diagnostic and prognostic information in myocarditis. Using an established animal model of myocarditis, the aim of this study was to measure myocardial T1 before the onset, in the acute and in the chronic phases of the disease and to compare its course with histological and immunohistochemistry findings. METHODS: Male young Lewis rats were immunized with 0.25 mg porcine myocardial myosin into the rear footpads on day 0. Native and contrast-enhanced ECG-triggered cardiac MRI examinations were performed before immunization on day 0 and on days 14, 21 and 35. Left ventricular function, pre- and post- contrast T1 parameters and LGE images were assessed using Small animal look-locker inversion recovery (SALLI). For each of the indicated time points a minimum of 4 rats were randomly sacrificed for pathological investigations including conventional histology (HE and Sirius-Red staining) and immunohistochemistry (CD 68) investigations. RESULTS: All immunized rats developed myocarditis (morbidity 100%). Histologically we observed increased wall thickness with biventricular macrophage-rich mixed inflammatory infiltrates. All rats with a histologically severe myocarditis showed increased native T1 and decreased post-contrast T1 of the myocardium. CONCLUSIONS: The assessment of native T1 and post-contrast T1 allows accurate differentiation between healthy myocardium and myocardium with inflammation and also between the acute and chronic phases of the disease.

A Universal Delivery System for Percutaneous Heart Valve Implantation.

Transcatheter heart valve implantation is an emerging technology and an alternative to surgical valve replacement. Most existing systems consist of valves sewn into balloon-expandable stents with a delivery catheter functioning with the specific valve only. The aim of this study was to develop a universally applicable delivery system (DS) for plane stents, valves sewn into both balloon-expandable and self-expandable stents and feasible for use with different access routes. A DS was designed and manufactured in five different diameters. The requirements were derived from the implants, the implantation technique and the cardiovascular geometry of the experimental sheep. The combination of a self-expandable Nitinol stent and a jugular access point represented the major challenge as both flexibility and rigidity of the DS were required. To fulfill these contradicting mechanical properties the sheaths were comprised of a soft outer polymer tube with a stainless steel coiled spring inside. Tissue-engineered and pericardial pulmonary valves were implanted. Also polymeric and balloon-expandable stents were delivered to various positions in the vascular system. The initial success rate was 70.5%. After refinement of the DS, a success rate of 83.3% was achieved with the remaining failed implantations resulting from inadequate sizes of the prostheses.

Cardiac MRI in patients with complex CHD following primary or secondary implantation of MRI-conditional pacemaker system.

OBJECTIVES: In patients with CHD, cardiac MRI is often indicated for functional and anatomical assessment. With the recent introduction of MRI-conditional pacemaker systems, cardiac MRI has become accessible for patients with pacemakers. The present clinical study aims to evaluate safety, susceptibility artefacts, and image reading of cardiac MRI in patients with CHD and MRI-conditional pacemaker systems. Material and methods CHD patients with MRI-conditional pacemaker systems and a clinical need for cardiac MRI were examined with a 1.5-T MRI system. Lead function was tested before and after MRI. Artefacts and image readings were evaluated using a four-point grading scale. RESULTS: A total of nine patients with CHD (mean age 34.0 years, range 19.5-53.6 years) received a total of 11 cardiac MRI examinations. Owing to clinical indications, seven patients had previously been converted from conventional to MRI-conditional pacemaker systems. All MRI examinations were completed without adverse effects. Device testing immediately after MRI and at follow-up showed no alteration of pacemaker device and lead function. Clinical questions could be addressed and answered in all patients. CONCLUSION: Cardiac MRI can be performed safely with high certainty of diagnosis in CHD patients with MRI-conditional pacemaker systems. In case of clinically indicated lead and box changing, CHD patients with non-MRI-conditional pacemaker systems should be considered for complete conversion to MRI-conditional systems.

Cardiovascular magnetic resonance predictors of clinical outcome in patients with suspected acute myocarditis.

BACKGROUND: The natural history of acute myocarditis (AM) remains highly variable and predictors of outcome are largely unknown. The objectives were to determine the potential value of various cardiovascular magnetic resonance (CMR) parameters for the prediction of adverse long-term outcome in patients presenting with suspected AM. METHODS: In a single-centre longitudinal prospective study, 203 routine consecutive patients with an initial CMR-based diagnosis of AM (typical Late Gadolinium Enhancement, LGE) were followed over a mean period of 18.9 ± 8.2 months. Various CMR parameters were evaluated as potential predictors of outcome. The primary endpoint was defined as the occurrence of at least one of the combined Major Adverse Clinical Events (MACE) (cardiac death or aborted sudden cardiac death, cardiac transplantation, sustained documented ventricular tachycardia, heart failure, recurrence of acute myocarditis, and the need for hospitalization for cardiac causes). RESULTS: The vast majority of patients (N = 143,70 %) presented with chest pain, mild to moderate troponin elevation and ST-segment or T wave abnormalities. Various CMR parameters were evaluated on initial CMR performed 3 ± 2 days after acute clinical presentation (LV functional parameters, presence/extent of edema on T2 CMR, and extent of late gadolinium enhancement lesions). Out of the 203 patients, 22 experienced at least one major cardiovascular event (10.8 %) during follow-up for a total of 31 major cardiovascular events. Among all CMR parameters, the only independent CMR predictor of adverse clinical outcome by multivariate analysis was an initial alteration of LVEF (p = 0.04). CONCLUSIONS: In routine consecutive patients without severe hemodynamic compromise and a CMR-based diagnosis of AM, various CMR parameters such as the presence and extent of myocardial edema and the extent of late gadolinium-enhanced LV myocardial lesions were not predictive of outcome. The only independent CMR predictor of adverse clinical outcome was an initial alteration of LVEF.

Alterations in creatine metabolism observed in experimental autoimmune myocarditis using ex vivo proton magic angle spinning MRS.

Experimental autoimmune myocarditis (EAM) in rodents is an accepted model of myocarditis and dilated cardiomyopathy (DCM). Altered metabolism is thought to play an important role in the pathogenesis of DCM and heart failure (HF). Study of the metabolism may provide new diagnostic information and insights into the mechanisms of myocarditis and HF. Proton MRS ((1)H-MRS) has not yet been used to study the changes occurring in myocarditis and subsequent HF. We aimed to explore the changes in creatine metabolism using this model and compare them with the findings in healthy animals. Myocardial function of male young Lewis rats with EAM was quantified by performing left ventricular ejection fraction (LVEF) analysis in short-axis cine images throughout the whole heart. Inflammatory cellular infiltrate was assessed by immunohistochemistry. Myocardial tissue was analyzed using ex vivo proton magic angle spinning MRS ((1)H-MAS-MRS). Myocarditis was confirmed histologically by the presence of an inflammatory cellular infiltrate and CD68 positive staining. A significant increase in the metabolic ratio of Tau/tCr (taurine/total creatine) obtained by (1)H-MAS-MRS was observed in myocarditis compared with healthy controls (21 d acute EAM, 4.38 (±0.23); 21 d control, 2.84 (±0.08); 35 d chronic EAM, 4.47 (±0.83); 35 d control, 2.59 (±0.38); P < 0.001). LVEF was reduced in diseased animals (EAM, 55.2% (±11.3%); control, 72.6% (±3.8%); P < 0.01) and correlated with Tau/tCr ratio (R = 0.937, P < 0.001). Metabolic alterations occur acutely with the development of myocarditis. Myocardial Tau/tCr ratio as detected by (1)H-MRS correlates with LVEF and is able to differentiate between healthy myocardium and myocardium from rats with EAM.

Assessment of cardiac function and myocardial morphology using small animal Look-Locker inversion recovery (SALLI) MRI in rats.

Small animal magnetic resonance imaging is an important tool to study cardiac function and changes in myocardial tissue. The high heart rates of small animals (200 to 600 beats/min) have previously limited the role of CMR imaging. Small animal Look-Locker inversion recovery (SALLI) is a T1 mapping sequence for small animals to overcome this problem. T1 maps provide quantitative information about tissue alterations and contrast agent kinetics. It is also possible to detect diffuse myocardial processes such as interstitial fibrosis or edema. Furthermore, from a single set of image data, it is possible to examine heart function and myocardial scarring by generating cine and inversion recovery-prepared late gadolinium enhancement-type MR images. The presented video shows step-by-step the procedures to perform small animal CMR imaging. Here it is presented with a healthy Sprague-Dawley rat, however naturally it can be extended to different cardiac small animal models.

Automated Detection of Complex Fractionated Atrial Electrograms In Substrate-Based Atrial Fibrillation Ablation: Better Discrimination with a New Setting of CARTO® Algorithm.

Background and purpose: Up until recently complex fractionated atrial electrogram (CFAE) ablation has been considered as time consuming and its achievement as challenging, especially for non experimented operators. Moreover, results of substrate ablation based on CFAE detection in atrial fibrillation (AF) are very disparate, mainly because of the operator's subjective electrogram visual analysis and the difficult distinction between CFAEs really involved in AF perpetuation from other CFAE. Automatic detection provided by 3D mapping system (CARTO® algorithm) can be helpful but is not selective enough, drawing too wide CFAE areas. We sought to demonstrate a better selectivity of a new CFAE algorithm setting in order to better discriminate CFAEs really involved in AF perpetuation from other CFAE. Methods and subjects: A population of 32 patients (60.4±12.7 years) with paroxysmal (n=3) AF (PAF), persistent (n=16) AF (PeAF) or long-standing persistent (n=13) AF (LSPeAF), and AF history =56±65 months, underwent CFAE ablation based on visual analysis. Before ablation, left atrium CFAE mapping was performed on CARTO® shortest complex interval (SCI) algorithm and reanalyzed after ablation with the two different settings: nominal (SCI 60-120ms/0.05-0.15mV) vs. customized setting (SCI 30-40ms/0,04-0.15mV). CFAE areas automatically detected by both settings (CFAE-CARTO® areas) were respectively measured. The decision to ablate CFAE was only based upon the operator's electrogram visual analysis taken as reference because of high AF termination rate (93.7%) due to operator's CFAE selection experience. These ablation points drawn reference-CFAE areas involved in AF perpetuation (ablation point=60mm2) allowing to compare the selectivity of the two previous automatic maps. Results: With the customized CARTO® SCI setting, we observed a significant reduction of CFAE areas detected by CARTO® (CFAE-CARTO® areas) and of the ablated CFAE surface inside non-CFAE CARTO® areas, (30.6±20.5cm2 vs. 68.8±24.5cm2, p<0.0001, and 1.86±1.82% vs. 3±3%, p=0.003). Furthermore the proportion of ablated areas/detected CFAE-CARTO® areas were higher with customized setting (38.2±19.6% vs. 20.4±17.5%, p=0.008). Conclusions: This new customized CFAE algorithm setting is significantly more selective than the nominal one and allows an automated detection of CFAE really involved in AF perpetuation truer to an efficient experienced operator's electrogram visual analysis.

Cardiovascular magnetic resonance of myocardial edema using a short inversion time inversion recovery (STIR) black-blood technique: diagnostic accuracy of visual and semi-quantitative assessment.

BACKGROUND: The short inversion time inversion recovery (STIR) black-blood technique has been used to visualize myocardial edema, and thus to differentiate acute from chronic myocardial lesions. However, some cardiovascular magnetic resonance (CMR) groups have reported variable image quality, and hence the diagnostic value of STIR in routine clinical practice has been put into question. The aim of our study was to analyze image quality and diagnostic performance of STIR using a set of pulse sequence parameters dedicated to edema detection, and to discuss possible factors that influence image quality. We hypothesized that STIR imaging is an accurate and robust way of detecting myocardial edema in non-selected patients with acute myocardial infarction. METHODS: Forty-six consecutive patients with acute myocardial infarction underwent CMR (day 4.5, +/- 1.6) including STIR for the assessment of myocardial edema and late gadolinium enhancement (LGE) for quantification of myocardial necrosis. Thirty of these patients underwent a follow-up CMR at approximately six months (195 +/- 39 days). Both STIR and LGE images were evaluated separately on a segmental basis for image quality as well as for presence and extent of myocardial hyper-intensity, with both visual and semi-quantitative (threshold-based) analysis. LGE was used as a reference standard for localization and extent of myocardial necrosis (acute) or scar (chronic). RESULTS: Image quality of STIR images was rated as diagnostic in 99.5% of cases. At the acute stage, the sensitivity and specificity of STIR to detect infarcted segments on visual assessment was 95% and 78% respectively, and on semi-quantitative assessment was 99% and 83%, respectively. STIR differentiated acutely from chronically infarcted segments with a sensitivity of 95% by both methods and with a specificity of 99% by visual assessment and 97% by semi-quantitative assessment. The extent of hyper-intense areas on acute STIR images was 85% larger than those on LGE images, with a larger myocardial salvage index in reperfused than in non-reperfused infarcts (p = 0.035). CONCLUSIONS: STIR with appropriate pulse sequence settings is accurate in detecting acute myocardial infarction (MI) and distinguishing acute from chronic MI with both visual and semi-quantitative analysis. Due to its unique technical characteristics, STIR should be regarded as an edema-weighted rather than a purely T2-weighted technique.

Assessment of diffuse myocardial fibrosis in rats using small-animal Look-Locker inversion recovery T1 mapping.

BACKGROUND: The concentration of gadopentetate dimeglumine in myocardium and blood can be assessed from T1 measurements and can be used to calculate the extracellular volume (ECV) of the myocardium. We hypothesized that diffuse myocardial fibrosis in a small-animal model could be quantitatively assessed by measuring myocardial ECV using small-animal Look-Locker inversion recovery T1 mapping. METHODS AND RESULTS: Sprague-Dawley rats (n=10) were subjected to continuous angiotensin-2 (AT2) infusion for 2 weeks via a subcutaneously implanted minipump system. Magnetic resonance imaging (MRI) was performed both before and after AT2 infusion. The MRI protocol included multislice cine imaging and before-and-after contrast small-animal Look-Locker inversion recovery T1 mapping and late gadolinium enhancement imaging. Myocardial ECV was calculated from hematocrit and T1 values of blood and myocardium. During the course of AT2 infusion, the mean±SD systolic blood pressure increased from 122±10.9 to 152±27.5 mm Hg (P=0.003). Normalized heart weight was significantly higher in AT2-treated animals than in control littermates (P=0.033). Cine MRI documented concentric left ventricular hypertrophy. Postcontrast myocardial T1 times were shortened after treatment (median [interquartile range], 712 [63] versus 820 [131] ms; P=0.002). Myocardial ECV increased from 17.2% (4.3%) before to 23.0% (6.2%) after AT2 treatment (P=0.031), which was accompanied by perivascular fibrosis and microscarring on myocardial histological analysis. There was a moderate level of correlation between ECV and collagen volume fraction, as assessed by histological analysis (r=0.69, P=0.013). CONCLUSIONS: In a small-animal model of left ventricular hypertrophy, contrast-enhanced T1 mapping can be used to detect diffuse myocardial fibrosis by quantification of myocardial ECV.

Correlation between AF substrate ablation difficulty and left atrial fibrosis quantified by delayed-enhancement cardiac magnetic resonance.

BACKGROUND: Studies have shown that the presence of left atrial (LA) fibrosis can be assessed by LA delayed-enhancement cardiac magnetic resonance (LA DE-CMR) and may be predictive of outcome after ablation for atrial fibrillation (AF). We sought to test the hypothesis that the amount of LA fibrosis evaluated by DE-CMR correlates with the difficulty of complex fractionated atrial electrograms (CFAE) ablation. METHODS: Twenty-two consecutive patients (86.4% nonparoxysmal AF) underwent substrate CFAE radiofrequency (RF) ablation (±Pulmonary veins isolation) with AF termination as the endpoint. LA DE-CMR was performed prior to ablation. A global index of DE was defined by an average of six LA segmental scores based on a four-grade scale (no enhancement to maximum enhancement). Time between first RF application and AF termination, and RF duration until AF termination, was recorded. CFAE area/total LA surface was also measured on CARTO maps (Biosense Webster, Diamond Bar, CA, USA). These measures served to evaluate ablation difficulty, and were correlated with CMR images by double-blinded analysis. RESULTS: Ablation restored sinus rhythm in 20 of 22 patients (91%), with a time to terminate AF of 140 ± 91 minutes. There was a significant correlation between the global averaged DE-CMR fibrosis grade and the electrophysiological substrate indexes such as "time to terminate AF" (Rho = 0.70, P = 0.0003), "RF duration until AF termination" (Rho = 0.65, P = 0.001), and a trend toward correlation with "CFAE area/LA surface" (Rho = 0.47, P = 0.03). CONCLUSIONS: LA DE-CMR can predict increased difficulty of CFAE ablation in AF. This tool may be beneficial in both selection of patients and ablation strategy.

Clinical significance of initial troponin I in the grey zone in emergency department chest pain patients: a retrospective pilot study.

AIM: 'Normal' range for cardiac troponin I (TnI) has changed with more sensitive tests, but the validity of low-level elevations is contentious. We aimed to describe the characteristics and outcome of patients with an initial TnI level 1-5 times the upper limit of normal. METHODS: Retrospective study of patients assessed for ACS with initial TnI level between 0.05-0.19 ng/ml. Data collected included demographics, clinical data, TnI levels and outcome. Primary outcome was the proportion of patients who had a serial TnI rise consistent with ACS. RESULTS: 72 patients were studied; median age 71, median TIMI score 3, 66.7% male. 35 patients (48.6%) had a TnI rise consistent with ACS. CONCLUSION: Approximately half of patients with initial TnI between 0.05-0.19 ng/ml had a TnI rise consistent with ACS. An initial TnI in this range is not, of itself, indicative of ACS. Clinical decision-making should be guided by clinical features and serial TnI measurement.