Diastolic function is an important component of left ventricular (LV) function which is often overlooked. It can cause symptoms of heart failure in patients even in the presence of normal systolic function. The parameters used to assess diastolic function often measure flow and are affected by the loading conditions of the heart. The interpretation of diastolic function in the context of congenital heart disease requires some understanding of the effects of the lesions themselves on these parameters. Individual congenital lesions will be discussed in this paper. Recently, load-independent techniques have led to more accurate measurements of ventricular compliance and remodeling in heart disease. The combination of inflow velocities and tissue Doppler measurements can be used to estimate diastolic function and LV filling pressures. This review focuses on diastolic function and assessment in congenital heart disease. Myocardial function has been extensively studied in the context of congenital heart disease. The focus to date has been on systolic function due to its importance and ease of measurement. However, the heart also needs to be adequately filled in order to function optimally, and this aspect of cardiac function is relatively under-investigated. The difficulties (as with systolic function) come when attempting to measure the relaxation of the myocardium while negating any effect of pre- or afterload. This is a difficult task and has led to the development of several tools which track myocardial movement independently of the usual flow-based parameters; the latter are heavily influenced by loading conditions. This article will summarize the current assessment of diastolic function using echocardiography and cardiac magnetic resonance (CMR) imaging in the normal heart and in patients with congenital heart disease.Diastole denotes the filling phase of the cardiac cycle. Filling is determined by myocardial relaxation as well as atrial contraction and atrial and ventricular compliance. Myocardial relaxation begins when the myofibrils return to an unstressed state and this precedes mitral valve (MV) opening (isovolumic relaxation). ATP is used to actively uncouple calcium from the contractile apparatus and return it to the sarcoplasmic reticulum. Active relaxation is only responsible for early diastolic filling, whereas compliance is important throughout filling and especially during atrial contraction.The early part of diastole is active relaxation, which is an energy-consuming process. The latter part is due to compliance or stiffness of the ventricle. Isovolumic relaxation time (IVRT) can be measured by invasive catheterization measurements. The index used in its measurement is the time constant of isovolumic pressure decline (τ). In non-invasive measurement, IVRT is the closest measurement to assess this value. However, as with all indices of diastolic function, the loading conditions must be taken into account.The stiffness of the myocardium also plays an important role in diastolic function. The mass of the left ventricular (LV) affects the stiffness as do the viscoelastic properties of the myocardium (cellular and extracellular components). Attempts are made to measure this increase in myocardial stiffness. However, the difficulty arises in the mechanism of measurement as well as the timing and nature of diastole. Flow-based measurements rely on a change in volume to occur, and so they are unable to quantify isovolumic relaxation as they assess only the last stage of diastole. There is also no universal measurement of diastole [equivalent to ejection fraction (EF) in systole] and torsion and dyssynchrony are difficult to quantify.As the ventricle stiffens, the velocity of blood flowing into the ventricle decreases. This downward trend would continue if not for compensation which takes the form of increased heart rate or increased diastolic filling pressure to maintain stroke volume (SV). The latter causes an increase toward normal filling velocities  and a prolongation of rapid filling. Ventricular elastance is an important marker for ventricular stiffness and is correlated with increased cardiac morbidity . IncreasThe LA is exposed to the LV loading pressure during MV opening and gradually remodels and increases in size. As LA remodeling takes place over time, it is a marker of the duration of DD as well as severity. The amount of dilatation also correlates with cardiovascular risk burden . There iThe mitral inflow velocity profile helps characterize LV inflow dynamics. It is best measured from the apical four-chamber view (in both children and adults) with the cursor placed across the MV just inside the LV. The E wave is the early diastolic filling wave seen on Doppler interrogation of the MV. It is caused by the drop of LV pressure below LA pressure during the cardiac cycle and is therefore influenced by LA pressure, LV compliance, and the rate of LV relaxation. The A wave, or atrial contraction wave, is immediately after the E wave on Doppler flow analysis. This is influenced by LV compliance and LA pressure and LA contractility rate. All MV inflow velocities are affected by preload and afterload. Under normal conditions, the E velocity is greater than A velocity Figure . As the E wave deceleration time is the rate at which the atrial and ventricular pressures equilibrate after onset of the E wave and is shorter in compliant ventricles (160–240 ms in adults). The IVRT is the period between closure of the aortic valve and opening of the MV. This is normally 70–90 ms long in adults and is prolonged in the case of decreased LV compliance. It is also affected by heart rate and ventricular function. It is best recorded from the apical five-chamber view with the cursor placed to record LV outflow tract velocities and LV inflow simultaneously.Pulmonary venous flow can enhance the information provided by MV inflow velocities. The pulsed-waved Doppler cursor should be placed in the right or left upper pulmonary vein from the apical four-chamber view, as distally into the vein as possible. The variables which are measured include peak systolic flow velocity (S), the peak diastolic flow velocity (D), peak atrial reversal flow velocity (AR), and AR duration (ARdur). The normal PV flow profile shows an initial, large S wave followed by a small D wave and then some retrograde flow during atrial contraction. As LA pressures increase, flow becomes predominantly diastolic and the S/D ratio reverses. A decreased systolic fraction of 40% is associated with elevated mean LA pressure of >15 mmHg . AR and An intraventricular pressure gradient exists between the base and apex of the ventricle, which acts to cause a suction effect on blood during diastole , 11. ThiThere are different grades of DD. Early (grade I/impaired relaxation) dysfunction is caused by a decrease in LV compliance, thereby leading to increased LV filling pressure. This delays atrial emptying and prolongs the E wave deceleration time DT > 240 ms). Atrial contraction becomes more vigorous, reducing the E/A ratio to <0.9. Worsening LV DD leads to increased atrial pressure and a decrease in the pressure gradient between the LA and LV, thereby leading to a shortened DT. The E/A ratio increases (0.9–1.5), but the E/A profile may appear normal . However, the e′ velocity on tissue Doppler imaging (TDI) (see below) remains low, giving a clue to the underlying abnormality . In grad40 ms. AtZ-scores are available for each age group in pediatrics  wave, the early diastolic (e′) wave, and the late diastolic wave caused by atrial contraction (a′). Normal values and diatrics .r = 0.87. PCWP correlated only weakly with E velocity but not e′ velocity. Patients with abnormal relaxation and pseudonormalization of the mitral inflow E/A ratio had a decreased e′ velocity (P < 0.001). In patients with DD, a saline bolus affects the E/A wave as measured by transmitral Doppler measurement but did not affect the e′ or e′/a′ ratios  corresponded to PCWP . In 125 ′ ratios . These sP < 0.001)  . This ha< 0.001) , 25.E/e′ ratio is an independent predictor of outcome in patients assessed 1–6 days after acute myocardial infarction . In a poMeasurement of LV torsion provides insight into an important mechanism of LV filling and ejection. LV rotation is sensitive to changes in regional and global LV function –31. MRI Strain is a dimensionless index of change in myocardial length in response to applied force and is expressed as a fraction or percentage change. Strain rate is the change in length over time (per second). By convention, myocardial lengthening or thinning is given a positive value. The techniques used to measure strain include echocardiography M-mode  or TDI , 40 as wStrain imaging aims to provide a high-resolution, real-time measure of myocardial deformation which is independent of loading conditions. A normal pattern of diastolic relaxation has been studied and described . Strain P = 0.024).In a study of 194 patients with chronic systolic HF, global longitudinal strain (GLS) correlated with worse NYHA class and higher NT-proBNP. It also correlated with LV structure and LVEF, as well as LV and RV DD. GLS also predicted long-term adverse events after adjustment for age, ischemic etiology, E/e′ septal, and NT-proBNP with HR 2.04 .It is also possible to evaluate tissue characteristics , includiMeasurement of dimensions and flow are evaluated similarly to echocardiographic measures, although volumes are more accurate. In tagging, the myocardium is labeled using selective saturation prepulses in specific myocardial regions perpendicular to the imaging plane. This allows strain and 3-D motion analysis .Increased ventricular stiffness and a change in the microscopic structure of the myocardium are inevitable parts of aging. This, coupled with changes in vascular stiffness, may lead to increased vulnerability in certain groups to developing symptomatic HF . TraditiThere are five main classes of CHD, which affect diastolic function. Pressure–overload lesions such as aortic stenosis and systemic hypertension cause a decrease in compliance due to hypertrophy. Volume overload leads to increased compliance up until a point, when hypertrophy or fibrosis occurs. Mixed pressure and volume overload can combine to affect compliance, such as in repaired Tetralogy of Fallot with some pulmonary valve stenosis and incompetence. Primary or secondary myocardial diseases can decrease compliance directly, such as in amyloidosis or restrictive cardiomyopathy. Transposition of the great arteries leads to a special situation in which the RV is faced with increased afterload and the LV with a much lower pressure than normal, both of which may cause decreased compliance . A summaAs with the left ventricle, the right ventricle can become stiff and restrictive due to hypertrophy. In Tetralogy of Fallot, the RV becomes a stiff conduit due to RV outflow tract obstruction, with poor diastolic function. This is evidenced by anterograde pulmonary flow with atrial contraction (end-diastolic forward flow in the PA). The presence of DD is a marker of poor short-term surgical outcome. In a study of 50 children with TOF (mean age 5.0 years), 24 had restrictive RV physiology as described. This correlated with lower E/A ratio and IVRT duration. DD also correlated with prolonged intensive care unit stay, longer duration of ionotropic support, and higher doses of diuretics. It was more commonly seen in patients after transannular patch repair . In a st2 slope)   . This is < 0.01) .n = 18) undergoing percutaneous device closure of their ASD, there were no significant changes in TDI and Doppler M-mode indices of diastolic function after closure. However, E wave velocity and E/e′ ratio at the MV annulus did increase significantly, thereby suggesting they are more load-dependent parameters , those with aortic stenosis or mixed disease were found to have DD, which was related to the degree of left ventricular hypertrophy (LVH). E/e′ correlated with LV end-diastolic pressure on catheterization. DD was found in 37% of all patients in the study, consisting of 37% of those with AS and 47% of those with mixed valve disease . IncreasCardiac magnetic resonance has a role in functional assessment of the LV in patients with AS. It is also used in tissue characterization and can quantify the degree of interstitial fibrosis and replacement fibrosis . There iAn incompetent aortic valve increases the end-diastolic volume of the left ventricle. The LV remodels to cope with this extra volume and becomes more compliant, so that diastolic pressures remain normal. Over time, decompensation may occur, in which case diastolic pressures increase as the LV loses the ability to compensate further . This isIn aortic regurgitation with normal diastolic function, MV inflow consists of predominant E wave filling and annular e′ is increased or normal due to increased LV SV. However, E/e′ is not increased and PA pressures are normal. With the onset of DD (DD), LV filling pressures are elevated on exercise initially and then at rest.Mitral stenosis results in increased LV filling pressure and reduced LV filling due to the restriction of blood flow through the MV. Most patients have normal intrinsic systolic and diastolic myocardial function. Some studies have found DD using conductance catheters, which are independent of loading conditions and acutely reversed after balloon valvuloplasty . The mecIn isolated MR, LV compliance usually decreases as it dilates to accommodate an increased volume . In acutTE–e′ can also be used to assess diastolic function irrespective of MR  and increase in transmitral E velocity . The e′ ve of MR .One theory of the mechanism of HFpEF is that it is caused by DD. Increased LV filling pressures cause back pressure on the pulmonary circulation, leading to symptoms of HF, including breathlessness. This is assumed to be the case as EF remains in the normal range, which is thought to denote normal systolic function . HoweverThe process of LV remodeling to compensate for decreased systolic function in these patients occurs due to feedback from the periphery, causing the heart to adapt with an increase in volume to maintain SV . TherefoA number of problems with the definition of HFpEF have been highlighted above; HF may not be reliably diagnosed using symptoms alone, and a preserved EF does not always correlate with normal systolic function. The notion of this type of disease being the definitive model for DD is flawed.Diastolic dysfunction is well recognized in hypertrophic cardiomyopathy, due to the active component of actin–myosin dissociation in the early filling phase and the passive compliance of the left ventricle –87. DD cDiastolic dysfunction is a characteristic of many types of congenital heart disease as well as of infancy and the aging heart. Thorough and thoughtful evaluation of diastolic function can help to explain symptoms and affect the treatment of patients with seemingly normal ventricular function. Ventricular function should be thought of as a combination of ventricular filling as well as systolic ejection so that the contribution of ventricular compliance to overall heart function is taken into account. Finally, loading conditions and effects of exertion should be taken into account during evaluation.Literature search and writing initial draft: DP. Critical revision and editing: MB. Final draft: DP.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Knowledge of the three-dimensional (3D) infarct structure and fiber orientation remodeling is essential for complete understanding of infarct pathophysiology and post-infarction electromechanical functioning of the heart. Accurate imaging of infarct microstructure necessitates imaging techniques that produce high image spatial resolution and high signal-to-noise ratio (SNR). The aim of this study is to provide detailed reconstruction of 3D chronic infarcts in order to characterize the infarct microstructural remodeling in porcine and human hearts.ex vivo. Systematic quantification of local microstructure was performed and the chronic infarct remodeling was characterized at different levels of wall thickness and scar transmurality. Further, a human heart with myocardial infarction was imaged using the same DTI sequence.We employed a customized diffusion tensor imaging (DTI) technique in conjunction with late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) on a 3T clinical scanner to image, at submillimeter resolution, myofiber orientation and scar structure in eight chronically infarcted porcine hearts p = 0.61, and inclination angle range: 111.0 ± 10.7° vs. 112.5 ± 6.8°, p = 0.61, infarcted/control wall), but at a higher transmural gradient of inclination angle that increased with scar transmurality (r = 0.36) and the inverse of wall thickness (r = 0.59). Further, the infarcted wall exhibited a significant increase in both the proportion of left-handed epicardial eigenvectors, and in the angle incoherency. The infarcted human heart demonstrated preservation of primary eigenvector orientation at the thinned region of infarct, consistent with the findings in the porcine hearts.The SNR of non-diffusion-weighted images was >100 in the infarcted and control hearts. Mean diffusivity and fractional anisotropy (FA) demonstrated a 43% increase, and a 35% decrease respectively, inside the scar tissue. Despite this, the majority of the scar showed anisotropic structure with FA higher than an isotropic liquid. The analysis revealed that the primary eigenvector orientation at the infarcted wall on average followed the pattern of original fiber orientation  contains supplementary material, which is available to authorized users. Myocardial infarction (MI) is a major cause of death, affecting millions of people worldwide . The occEarly renditions of myocardial fiber structure were based on sectioning approaches . These mex vivo. For the infarcted porcine hearts, this technique was used in conjunction with high-resolution T1-weighted late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR), to reconstruct the ventricular fiber organization and scar geometry in the same heart at image resolution and SNR higher than previously achieved % range of inclination angle distribution; imbrication angle mean, the average of the imbrication angles within a segment; left-handed ratio (LH ratio), the ratio of the number of voxels in which inclination angle < −15° to the total number of voxels within a segment; circumferential ratio, same ratio but calculated for the voxels with −15° < inclination angle < 15°; and right-handed ratio (RH ratio), same ratio but for voxels with inclination angle > 15°. We also quantified local intervoxel incoherency in eigenvector arrangement corresponding to both the inclination and imbrication angles  and control (n = 4) hearts (per heart statistics). The same statistics was performed on the pooled voxel or segment data (per voxel/segment statistics). All the data is presented as mean ± standard deviation (STD). The statistics presented in the text of the manuscript are from the per heart analysis, unless stated otherwise. Further, Pearson correlations were calculated to study the pair-wise associations of slope, inclination angle range, wall thickness, and scar transmurality in the infarcted segments from porcine hearts.3. To examine infarct remodeling in the human heart, fiber angle measurement and eigenvector visualization were performed in the same way as in the porcine hearts.In addition to the porcine hearts, an intact human heart was procured through the National Disease Research Interchange . This heart was from a donor with a history of MI . The human heart specimen had already undergone fixation process at the time of acquisition and hence was not imaged using LGE-CMR (fixation time from harvest: 7 h). It was imaged using the same diffusion tensor imaging sequence at the resolution of 0.5 × 0.5 × 1.0 mm3 in MI vs. 41 ± 25 cm3 in normal hearts). The normal hearts had an average wall thickness of 7.2 ± 1.2 mm; by comparison, the average wall thickness in the infarcted porcine hearts was 5.1 ± 1.2 mm for the infarcted regions and 9.5 ± 1.8 mm otherwise. The scar volume comprised 10.1 ± 7.6% of the LV myocardial volume.The eight infarcted porcine hearts demonstrated significant global remodeling with changes in LV mass and LV blood volume  and normal tissue . The MD value was higher in fibrotic tissue (9.08 ± 0.72 × 10−4 mm2/s) as compared to non-fibrotic  and normal tissue . In addition, the pooled distributions of diffusivity measures  and that on average, the eigenvectors run parallel to the wall with a small mean imbrication angles . In addition, there is an increase in both the inclination incoherency  and the imbrication incoherency metrics  at the infarcted regions. The transmural slope of the inclination angle showed an average increase inside the infarcted segments  with a lower r-squared of the linear regression fit in the infarcted segments . When only the infarcted segments with a higher range of scar transmurality [0.67–1.00] compared to the control segments, the increase in slope was more substantial, and statistically significant , as well as a 13% decrease in circumferential-ratio  and a 26% decrease in RH-ratio 0.23 ± 0.06, p =0.041).Characteristics of the microstructural remodeling in the infarcted segments are presented in Table Figure 5), non-fibrotic inside the infarcted segments (n ~ 1.4 × 106), and control (n ~ 8.6 × 105) were plotted together as a function of normalized wall depth, an interesting trend emerged: the fibrotic voxels tended to cluster within the endocardial half of the wall  resulted in an average of 8 voxels across the infarcted wall, allowing for the characterization of the structural remodeling in the zone of infarct, a task that has previously been particularly challenging for DTI due to significant infarct wall thinning and limited image resolution [In this work, we studied chronic MI microstructural remodeling in eight porcine hearts and in a human heart non-destructively at submillimeter resolution. We examined the hearts’ fibrous structure using a customized DTI sequence on a clinical scanner (to accommodate the large specimen) that allowed acquisition of data over long scanning times with high image stability . This, isolution . ImportaThe measurement of diffusion scalars in infarcted porcine hearts demonstrated an average of 43% increase in MD and a 35% decrease in FA inside the scar. Similar changes in MD and FA have been reported in DTI studies of myocardial infarcts in various species , 25, 26.The presence of diffusion anisotropy allowed us to employ the diffusion eigenvectors to investigate the anisotropic organization of the collagenous scar. We found that, on average, the orientation of the eigenvectors at the infarcted segments followed the pattern of the original fiber orientation, i.e. left-handed fibers at the epicardium to right-handed fibers at the endocardium. This result is consistent with previous findings in rats  and sheeIn this study, we found an increase in the proportion of left-handed primary eigenvectors inside the infarcted segments of porcine hearts, which had also been observed in two previous studies of human hearts , 18. We After MI, the organization of collagen fibers in the scar is influenced by structural and mechanical factors . The oriAccurate structural data is essential for the construction and validation of whole-heart computational models –35. ThesThis study has several limitations. First, the LAD reperfusion infarct induction protocol in porcine hearts may render our findings not entirely applicable to all chronic infarctions in the human. Second, although the main findings from the analysis of the porcine hearts regarding the preservation of eigenvector orientation and the increase in the transmural slope were in agreement with the those of the human heart in this study, the single human specimen was not sufficient for a full characterization of infarct remodeling in human hearts and was only a simple existence demonstration. Future studies are needed to investigate this in a larger number of samples. Also since this specimen did not undergo LGE imaging, we were not able to accurately delineate the infarcted area and provide systematic analysis of the remodeling in this heart. Third, despite submillimeter resolution of the imaging with average of ~8 voxels across the wall in the infarct, we excluded the regions with wall thickness less than 2 mm to ensure reliable measurement of transmural angle profile with at least ~4 voxels across the wall; this excluded around 10% of the infarcted wall. Finally, while the fixation process could have affected the baseline values of diffusivity such as FA and MD in our study , it has The application of 3D DTI and LGE-CMR revealed the fiber orientation and scar geometry in infarcted porcine hearts at an unparalleled resolution and SNR. The results demonstrated preservation of eigenvector orientation, with a higher transmural gradient of inclination angle at the thinned wall of infarct. Detailed information of post-infarction remodeling obtained in this study could pave the way for generation of accurate whole-heart models of infarcted hearts to investigate the mechanistic links between the structure and electromechanical function, and thus may lead to improvements in therapies after myocardial infarction.


Myocardial tissue characterization with both native T1 mapping and T1 mapping following gadolinium based contrast agents (T1 enhanced) has emerged as an important asset of CMR imaging . Native Purpose: To examine the effectiveness of CMR myocardial characterization by native T1 and T1 enhanced mapping in a heterogenous group of pediatric patients with signs concerning for cardiomyopathy or myocarditis.TM, remainder used 1.5T IngeniaTM scanner .We reviewed our initial experience of an ongoing study with T1 mapping in 10 subjects (aged 15.4 ± 2.5 years). All patients underwent CMR due to signs suggestive of cardiac disease. Cohort included 4 patients with concern for myocarditis, 4 with concerns for HCM, and 2 with concern for myocardial ischemia. 3 of the acquisitions were made in 3T AcheivaTM). T1 mapping (modified Look Locker - MOLLI) sequence was performed prior to contrast injection and post contrast (15 minutes after contrast) injection. The MOLLI sequence had a bSSFP readout TR/TE/α = 3/1.5 ms/20°; A 5,5,3 inversion acquisition scheme was used, and acquisition time was 13 heart beats.Acquisition Protocol: All clinically indicated MRI sequences were performed, including delayed enhanced phase sensitive inversion recovery sequence, after injection of contrast  was significantly higher than the native T1 in all other patients (n = 4), 1094 ± 38 ms vs. 986 ± 23 ms (p < 0.05). Likewise, the septal T1 enhanced of patients who were diagnosed with HCM (n = 3) was lower than the remaining patients (n = 4), 460 ± 16 ms vs. 533 ± 16 ms (p <0.05).Myocardial characterization may be an effective tool in pediatric patients with a potential diagnosis of cardiomyopathy or myocarditis. Within a heterogenous group of patients, the native T1 was able to distinguish myocarditis from other potential cardiac disorders, while the enhanced T1 was able to distinguish HCM.


Autosomal dominant polycystic kidney disease (ADPKD) is the most common familial renal disorder. Left ventricular non-compaction cardiomyopathy (LVNC) is a rare cardiac condition resulting primarily from interruption of the normal embryonic process of myocardial compaction. Genes responsible for ADPKD have been linked to disorganized myocardial arrangement in animal models. In addition, there are multiple published case reports of ADPKD and LVNC occurring in the same patient. Therefore, we sought to examine possible association of ADPKD with LVNC in a large cohort of patients using cardiac magnetic resonance (CMR) imaging.In this descriptive, retrospective study, we analyzed 126 CMR scans from 36 patients with known ADPKD, who had undergone serial CMR testing at Beth Israel Deaconess Medical Center, Boston, MA as part of HALT-PKD trial. We examined for both the Peterson's CMR criteria (non-compacted/compacted ratio > 2.3 in diastole on long-axis images) and Jenni's echocardiographic criteria (non-compacted/compacted ratio > 2.0 at end-systole on short-axis images) in order to identify potential cases of LVNC. A random sample of 10 scans was independently analyzed by a second reader to assess for inter-observer reproducibility.None of the patients (0/126 scans) met the diagnostic criteria for LVNC. There was 100% inter-observer agreement between the two readers in the 10 random scans analyzed.In this study of 36 patients with ADPKD, we found no association between ADPKD and LVNC using cardiac magnetic resonance imaging. These data suggest that the case reports in the literature likely represent spurious/random incidents of the coexistence of both diseases rather than a true association.


Children with a single systemic right ventricle, such as in hypoplastic left heart syndrome (HLHS), frequently experience reduced exercise capacity. Elucidating the causes could help with optimising treatment strategies.Prospective data from 10 consecutive symptomatic patients with HLHS undergoing clinical cardiac magnetic resonance with catheterisation (XMR) were analysed. Mean age 8.6 years (range 3.5–11.6 years), mean time since Fontan completion 5.5 years. MR-compatible catheters were placed in the systemic right ventricle and branch pulmonary arteries to record pressures at rest, with dobutamine infusion at 10 mcg/kg/min and at 20 mcg/kg/min. Cine short-axis stacks of the ventricle were performed at each condition and used to construct pressure–volume loops.p < 0.01) with no further rise at peak stress despite a further, albeit, blunted rise in heart rate (p = 0.002). A fall in stroke volume occurred (p = 0.014) despite good contractility  and a well-coupled ventriculo-arterial ratio. End-diastolic pressure and early active relaxation, markers of diastolic function, were normal at rest. However, preload fell at peak stress (p < 0.008) while pulmonary vascular resistance (PVR) was low throughout. This group of HLHS patients demonstrated a fall in SV at peak stress, coinciding with a fall in preload.Compared to rest, cardiac index increased with low-dose dobutamine (Markers of systolic and diastolic function remained normal. Failure to adequately fill the ventricle implies a ceiling of maximal flow through the Fontan circuit despite low PVR. Cardiac output is augmented only through increasing heart rate In this study, we assessed a group of children with HLHS exhibiting symptoms of diminished exercise capacity. We focused on assessing ventricular energetics and function while applying incremental dobutamine stress to study the changes in physiology through a range of heart rates. We hypothesized that stepwise increments of dobutamine might unmask ventricular dysfunction only seen at the highest heart rates helping us to further understand the reasons for a blunted response in CI.22.1Prospective data were collected from 10 consecutive studies on patients with HLHS undergoing clinical XMR. Patients were referred by their clinician for assessment of exercise intolerance. All had undergone completion of a total cavopulmonary anastomosis at our institution and were scanned under general anaesthesia using low-dose inhaled sevofluorane with remifentanyl while maintaining normocarbia as per institutional preference . All subjects underwent cardiac magnetic resonance imaging (MRI) on a 1.5-Tesla scanner  using a two-channel coil. The research protocol is outlined in 2.2A fluid filled magnetic resonance (MR)–compatible catheter was placed in the systemic RV under X-ray guidance. A second MR-compatible catheter was placed in one of the branch pulmonary arteries. A mean pulmonary artery and mean pulmonary capillary wedge pressure were recorded and the difference used to calculate the trans-pulmonary gradient. Pressures were recorded on a haemodynamic tracer system . Patients received a standard heparin bolus for anti-coagulation, which was monitored using activated clotting time. Once the catheters were in-place, the patient was transferred to the MR scanner to undergo simultaneous pressure and volume measurements 2.3A retrospectively ECG-gated balanced-steady state-free precession (bSSFP) cine short-axis stack planned parallel to the atrio-ventricular valve plane of the systemic ventricle was performed. Images were acquired during end expiratory breath-holds covering apex to base. Typical imaging parameters: TR = 3.0–3.6 ms; TE = 1.5–1.8 ms; parallel imaging (SENSE) factor 2; flip angle 60°; field of view 200–400 mm, slice thickness 6–8 mm depending on patient size, in-plane resolution 1.3–2.0 mm; acquired temporal resolution 30–40 phases, breath-hold duration 5–7 s per slice, 10–14 slices to cover the heart.2.4A free-breathing retrospectively ECG-triggered two-dimensional (2D) phase contrast (PC) flow was acquired orthogonal to the ascending aorta at the level of the right pulmonary artery (RPA) and additionally orthogonal to the superior and inferior vena cavae (SVC and IVC) with NSA 3, spatial resolution 1.5 × 1.5 × 6 mm, acquired temporal resolution 30 phases. This was used to determine aorto-pulmonary collateral (APC) flow.2.5Invasive ventricular pressures, pulmonary, and pulmonary capillary wedge pressures were recorded at rest and repeated with infusion of dobutamine first at 10 mcg/kg/min and then at 20 mcg/kg/min. Simultaneous cine short-axis stacks of the ventricle with aorta, left pulmonary artery (LPA), and right pulmonary artery (RPA) 2D PC flow were performed during each condition. The protocol was terminated if the patient became haemodynamically unstable .2.6Analysis of CMR volumetric and flow data was performed using a Viewforum workstation . Segmentation of the ventricular cavity involved manual tracing of endocardial contours for each slice at all time points. The position of the atrio-ventricular valve was confirmed by linking the short-axis stack to a long-axis view of the ventricle. Calculation of 2D PC flow stroke volume (SV) was performed by contouring a region of interest encompassing the vessel for all phases of the cardiac cycle.Aorto-pulmonary collateral (APC) flow was calculated as follows:Q = flowAPC = aorta-pulmonary collateralAo = ascending aortaSVC = superior vena cavaIVC = inferior vena cavamax) estimation method using the average of multiple pressures es). The slope of the relationship of EDV to end-systolic pressure (ESP) defines the elastance of the artery (Ea). Ventriculo-arterial coupling is represented by the ratio of Ees to Ea. The area within the pressure–volume loop was used to establish ventricular stroke work and multiplied by HR to calculate power. Tau (τ), the early relaxation constant, was calculated from the reciprocal of the natural logarithm of the early maximal fall in ventricular pressure during diastole.Pressure–volume loops were constructed for each condition. This is shown in La Place formula Preload values were taken from multiple averaged measurements and calculated using a modified σ = mean end-diastolic wall stress2)P = RV pressure h = wall thickness (cm)The branch pulmonary artery flows and trans-pulmonary gradient were used to calculate pulmonary vascular resistance 2.7t tests. Throughout, a p value of < 0.05 was considered significant. Inter-user variabilities for manual segmentation of CMR were determined by intra-class correlation coefficients using a two-way random model with absolute agreement.Statistical analysis was performed using SPSS version 22. Tests of normality were performed using the Shapiro–Wilk method. Continuous variables were expressed as mean ± SD. One-way analysis of variance (ANOVA) was used to assess differences between rest and each condition of dobutamine using Bonferroni-adjusted post hoc 3Ten consecutive studies were performed with all patients having undergone staged palliation for HLHS. All were prospectively recruited and all tolerated the full dobutamine protocol. 3.12) compared to published values for healthy children p = 0.01). This was driven solely by a rise in HR (p = 0.0001). SV remained the same as although ESV fell (p = 0.001), there was a similar fall in EDV (p = 0.0001). At maximum stress with 20 mcg/kg/min dobutamine, there was no further increase in CI, HR rose (p = 0.002); however, SV fell (p = 0.045) as the fall in EDV was greater than the fall in ESV.3.2es) increased 67% during the low-dose dobutamine stress (10 mcg/kg/min) (p = 0.045) with no further increase with dobutamine 20 mcg/kg/min. This was accompanied by a stepwise increase in afterload , which reached significance at dobutamine 20 mcg/kg/min (p = 0.012).es:Ea) was 1.45 ± 0.2 at rest. It remained adequately coupled during administration of incremental doses of dobutamine due to increases in both contractility and afterload.The ventriculo-arterial coupling ratio (E3.3p = 0.001) but plateaued with dobutamine 20 mcg/kg/min as the late fall in SV offset any further incremental rise in power (in power b.3.4p = 0.99). There was an overall stepwise improvement in myocardial relaxation as demonstrated by the fall in Tau, which reached significance at dobutamine at 20 mcg/kg/min (p = 0.038).Parameters of diastolic function were normal at rest  with an 3.5p = 0.008). The relationship of preload to SV is shown in 2) and remained unchanged throughout  was 0.97 (0.80–0.99) for EDV, 0.95 (0.82–0.980) for ESV, 0.95 (0.82–0.98) for SV, and 0.89 (0.58–0.97) for EF.4In this study, we used XMR to gain further insights into the causes of reduced functional status in patients with HLHS post-Fontan. We hypothesised that abnormalities in systolic or diastolic indices of the systemic right ventricle might become apparent with application of stepwise increments of dobutamine stress and these may in part explain the abnormal CI and blunted response to stress previously demonstrated in the literature 4.1Van De Bruaene et al. Previous studies have shown 4.23 ± 4 × 103 dynes/cm2) In Fontan circulation, the absence of a subpulmonary ventricle might be expected to reduce the preload of the ventricle Schmitt et al. used a similar method for quantifying PVR The observed preload response was not caused by an abnormal PVR. Baseline PVR was normal and remained low throughout the procedure. 4.3Previous studies using load-dependent markers of function have suggested that systolic function as measured by EF is reduced in those with single systemic RV circulations compared to those with single systemic LV circulations 4.4Findings from echocardiographic-based studies suggest diastolic abnormalities exist in 67–72% of patients undergoing Fontan 4.5es. Under resting conditions, the systemic RV has a ventriculo-arterial coupling ratio that compares favourably to the healthy LV The pressure–volume loops  for the 4.6Schmitt and colleagues 5In those with a Fontan circulation, peripheral muscle contractions and respiratory effort play a prominent role in driving blood through the systemic veins ChanavazThe patients in this study were anaesthetised using sevofluorane and remifentanil. We tried to manage the patients with the lowest doses of these drugs to maintain effective anaesthesia. The effects of sevofluorane on loading conditions and contractility have been extensively studied in animals The systemic RV is not a true prolate ellipsoid. Although other formulas for preload exist specific to the RV, in HLHS, the septal wall is thought of belonging to the systemic RV so a modified formula for idiopathic hypertension is not applicable The single-beat estimation method was originally conceived for the LV and has been validated in the RV. Early work on the systemic RV has been performed 6Children with HLHS-Fontan display a blunted response in CI and a fall in SV at peak stress due to a failure to adequately preload the heart. The HR-driven response makes this an energetically costly process. PVR remains low, systolic and diastolic functional indices tend to be normal, and the ventricle is well coupled to the hydraulic load. In young patients introducing measures that focus on improving the preload of the heart may offer the most benefits.Wellcome Trust and EPSRC; grant number WT 088641/Z/09/Z) and the BHF Centre of Excellence (British Heart Foundation award RE/08/03).The Division of Imaging Sciences receives support as the Centre of Excellence in Medical Engineering  comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust.None.


Most patients with implantable cardioverter-defibrillator (ICD) implantation fail to utilize the device resulting in increasing societal costs and patient exposure to device morbidity. We sought to determine whether volumetric cardiovascular magnetic resonance (CMR) left ventricular (LV) spherical remodeling predicts future ventricular arrhythmias in primary ICD patients with reduced LV ejection fraction (EF).Sixty-eight consecutive patients with transthoracic echocardiographic LVEF <35% referred for CMR prior to ICD implantation for primary prevention of sudden death were identified. Sphericity index was measured as the ratio of LV end-diastolic volume (from cine short axis stack) to the volume of a sphere with a LV end-diastolic 4-chamber length diameter.p = 0.007). In addition, dichotomized volumetric CMR-derived sphericity index ≥0.57 carried a 4-fold hazard risk for appropriate ICD therapy, controlling for age and LVEF . When sphericity index, LVEF and mass index were used in combination, important incremental prognostic information was achieved .During a median follow-up of 55 months , 15 patients (22%) received appropriate ICD therapy. Multivariable Cox’s proportional hazard modeling identified increased CMR-derived sphericity index as the strongest independent predictor of appropriate ICD therapy (hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.02 to 1.16; The combined assessment of LV geometry, mass index and systolic function may provide incremental prognostic information regarding ventricular arrhythmia requiring appropriate ICD therapy in primary prevention patients with reduced LVEF. The implanted cardioverter-defibrillator (ICD) is an established therapy for reducing mortality in patients with life-threating ventricular arrhythmia (VA) , 2. CurrLate gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) is the gold standard for the assessment of regional myocardial fibrosis and may help predict VA and sudden cardiac death (SCD) –12. HeteWe retrospectively identified 71 consecutive patients who had undergone ICD implantation for primary SCD prevention who had a comprehensive CMR study before ICD implantation. Subjects were identified by querying the Beth Israel Deaconess Medical Center clinical CMR and ICD databases from April 2004 to December 2014. Exclusion criteria were: 1) idiopathic outflow tract ventricular tachycardias, 2) Brugada, and Long QT syndromes, 3) hypertrophic, inflammatory, infiltrative, and arrhythmogenic cardiomyopathies. Ischemic etiology was defined as the presence of any epicardial coronary artery dimeter stenosis >70%, a history of myocardial infarction, or a subendocardial based LGE pattern. Patient demographics and clinical follow-up records from the hospital electronic medical records were reviewed. The study was carried out with Beth Israel Deaconess Medical Center Institutional Review Board approval which waived written informed consent.2; matrix, 160 × 160; and spatial resolution of 2 mm2). In 35 patients, LGE was performed using a 3D phase sensitive inversion recovery sequence (PSIR) .All CMR images were acquired on a 1.5 Tesla scanner  equipped with a 5-element or 32-element cardiac coil. The CMR protocol included cine and LGE. To assess LV/right ventricular (RV) myocardial function, geometry and mass, 10 to 12 short-axis stack cine images and 4-chamber long axis image were acquired using a cine balanced steady state free precession sequence  . Ten to CMR images were analyzed by a investigator blinded to ICD therapy using commercial workstations . At end-diastole and end-systole, epi- and endocardial LV borders were manually traced from contiguous short-axis cine images covering the LV apex to mitral valve plane to calculate LV and RV end-diastolic volume (EDV) and end-systolic volume, stroke volume, and ejection fraction (EF). LV mass was calculated as the sum of the myocardial volume multiplied by the specific gravity 1.05 g/mL) of myocardial tissue. Sphericity index was calculated as the ratio of the LV EDV to the volume of a sphere with the diameter of the LV end-diastolic long axis from a 4-chamber cine image , anti-tachycardia pacing followed by shock for fast ventricular tachycardia (VT), and a monitored zone for slower VT. Exact therapy settings were adjusted at the discretion of the implanting physician. Devices were interrogated at 1 and 3 months after implantation and every 6 months thereafter in the Device Clinic, during which the device was interrogated, and adjudication of stored ICD electrograms was performed by an electrophysiologist blinded to CMR findings (HI). The primary end point for our study was the delivery of appropriate ICD therapy for VT, VF, or sustained VT > 30-s duration as documented by the device and recorded in the patient’s online medical record.p value <0.05 considered significant. Kaplan-Meier curves were used to estimate the distribution of time to the first episode of appropriate ICD therapy or sustained VT. Differences between time-to-event curves were compared with the log-rank test. Univariable Cox regression models were used to assess the association between each variable and the primary end point. For multivariable modeling, using the rule of thumb of having between 5 and 10 outcomes per predictor (we had 15 with appropriate ICD therapy), we decided to include 2 most significant variables from the univariable models (LVEF and sphericity index) and 1 covariate (age). We then used stepwise-forward selection which yielded only sphericity index in the final model. From this final model, we then searched for the optimal threshold of sphericity index (0.57) that yielded the largest area under the receiver operating characteristic (ROC) curve. Using this threshold, we then dichotomized the scale of sphericity index into binary and assessed the associations of sphericity index ≥0.57 to appropriate ICD therapy adjusted to age and LVEF. All reported associations in this study are hazard ratios (HR) and their corresponding 95% confidence intervals (CI). Reclassification of patients was determined using net reclassification improvement analysis for appropriate ICD therapy and obtained by adding sphericity index and LV mass index (LVMI) status to the model based on LVEF. Because no conventional cut-off values exist for the onset of ICD therapy in such population, risk categories were used to stratify patients into low-risk (0% to <10%), intermediate risk (10% to <20%) and high-risk (≥20%) categories. Categorical net reclassification improvement was computed together with integrated discrimination improvement.Statistical analyses were performed using SPSS  and R version 3.2.3 . Continuous variables are expressed as mean ± standard deviation (SD) or median [quartiles] as appropriate, and compared using an unpaired Student’s t-test or Mann-Whitney nonparametric test if not normally distributed. Categorical variables were reported as counts and percentages, and compared using a chi-square test. To compare the relationship between the sphericity index and LVEF, a regression analysis was performed, and an analysis of covariance was used to test for equality of the regression slopes between patients with and without appropriate ICD therapy. All tests were 2 sided and 2 in men i ≥ 78 ml/m2 in female). Sphericity index moderately and positively correlated with LVEDVI  and negatively correlated with LVEF , but did not correlate with LVMI .Of the 71 identified patients, 3 patients (4%) were lost to follow-up and were excluded, leaving 68 patients for the final analysis. Their clinical and CMR characteristics are summarized in Tables p = 0.51). There was a trend for patients with an ischemic cardiomyopathy to receive appropriate ICD therapy . Patients with and without appropriate ICD therapy had similar baseline age, gender, history of hypertension, diabetes mellitus and dyslipidemia , while patients that received appropriate ICD therapy tended to have a higher NYHA functional class (p = 0.05). There was a trend for higher LV end-systolic volume and lower LVEF in patients with appropriate ICD therapy . Patients with ICD therapy had significantly lower RVEF (p = 0.02). LVMI was significantly higher in patients with appropriate ICD therapy compared with that in patients without ICD therapy (p = 0.01). In addition, LV sphericity index was significantly higher in patients with appropriate ICD therapy (p = 0.001). Figure p = 0.11, 0.13, 0.18 and 0.17, respectively). There was a trend for heterogeneous scar (2-4SD) to more likely receive appropriate ICD therapy (p = 0.09). RWT was not associated with the presence of LGE , 15 patients (22%) received appropriate ICD therapy. Appropriate ICD therapies were delivered in 11/45 (24%) with conventional ICDs and 4/23 (17%) with biventricular ICDs (p = 0.007). Although reduced LVEF was an important predictor of appropriate ICD therapy in univariate analysis, LVEF was no longer significant in multivariate analysis because of significant negative correlation with sphericity index   . Furthermore, the addition of sphericity index and LVMI values to LVEF yielded 4 correct (up) reclassifications and 2 incorrect (down) reclassifications in the 15 patients of receiving ICD therapy. Additionally, 19 correct (down) reclassifications and 4 incorrect (up) reclassifications occurred in the 53 patients who did not receive ICD therapy. Overall, the integration of sphericity index and LVMI values provided the improvement in risk stratification (net reclassification index (NRI) 0.42; 95% CI 0.06 to 0.77, p = 0.02). Reduced RVEF appeared more likely to predict appropriate ICD therapy  and RVEF <40%  demonstrated a strong univariate association with appropriate ICD therapy . However, RVEF did not significantly predict appropriate ICD therapy beyond LVEF.Univariable and multivariable analyses of clinical and CMR parameters for appropriate ICD therapy are summarized in Table In this retrospective study of 68 consecutive patients referred for CMR prior to primary prevention ICD implantation, we demonstrate that: 1) CMR LV sphericity index is the strongest independent predictor of ventricular arrhythmias requiring appropriate ICD therapy, 2) CMR-derived sphericity index ≥0.57 is associated with a higher risk of appropriate ICD therapy adjusted for age, gender, and LVEF, 3) the integration of sphericity index to LV function assessment provides additional prognostic information regarding appropriate ICD therapy. Importantly, sphericity index can be easily derived and without a cost of additional scan time or need for gadolinium contrast.Echocardiographic (echo)-derived LV sphericity is a marker of LV systolic dysfunction and exercise tolerance in heart failure , 22, an increased LVM/LVEDV appeared likely to receive appropriate ICD therapy. Furthermore, our observation was that the presence of LGE was not associated with regional wall thickness as well as RWT. This finding supports the results of Shah et al. who found myocardial thinning does not necessarily indicate scar tissue and might improve after revascularization in patients with coronary artery disease [In a recent 2D echo study by Biton et al. , decreas disease . In isch1 or extracellular volume (ECV) mapping allows for assessment of diffuse myocardial fibrosis. We have recently reported the native T1 is useful for predicting VA in non-ischemic cardiomyopathy [1 or ECV mapping, provide incremental value to LGE and LV function/geometry for the prediction of future VA risk in patients with reduced LVEF receiving primary prevention ICD therapy.Our results showed the presence and extent of LGE was not a predictor for appropriate ICD therapy. Although focal scar evident by the presence and extent of LGE is known to be associated with increased risk of VA and ICD therapy , 30–32, myopathy . FurtherInterestingly, we found RVEF <40% carried a 4-fold unadjusted hazard risk for appropriate ICD therapy, which implies a clinical importance for the accurate assessment of RV function by CMR. However, RV dysfunction was mainly related to indices of LV function and not associated with VA beyond LVEF and the presence of LGE. This finding may reflect the presence of other subclinical conditions, such as RV ischemia or post-capillary pulmonary hypertension that affect RV function and have negative impact on VA.Our study has several limitations. It is a retrospective study with a relatively small sample size, thus, the results should be interpreted cautiously. We studied patients referred for CMR prior to undergoing primary prevention ICD implantations spanning a period of 10 years. Heart failure management might have changed over the course of this follow-up period. We assessed CMR parameters at a single time. Changes in sphericity index may be more predictive of future VA than a single baseline measurement. Device choice and programming was not standardized and was left to the discretion of the operator.CMR-derived sphericity index may be an important predictor of VA and provide additive risk stratification for primary prevention ICD in patients with LV systolic dysfunction. Prospective, large multicenter studies are warranted to examine this easily obtained CMR parameter in the selection of patients for primary prevention ICD therapy.


Acute myocarditis (AM) is an inflammatory disease of the heart muscle. Clinical presentation and outcome are variable, ranging from asymptomatic to fulminant myocarditis (FM), presenting with decompensated heart failure or cardiogenic shock needing inotropic or mechanical circulatory support. Cardiac magnetic resonance (CMR) is increasingly employed in the diagnosis and follow-up (f.u.) of AM. We investigated the differences in functional parameters evaluated with CMR between patients (pts) presenting with FM versus non fulminant AM (NFM), at baseline and f.u.We retrospectively analyzed consecutive pts with AM who underwent CMR  within 30 days from clinical presentation. Cine, STIR T2-weighted and late-enhancement images were acquired on matching planes. CMR diagnosis of AM was based on Lake Louise Criteria. Indexed LV end-diastolic (LVEDVi) and end-systolic (LVESVi) volumes, LV ejection fraction (LVEF), indexed LV mass (LVmi), indexed RV end-diastolic (RVEDVi) and end-systolic (RVESVi) volumes and RV ejection fraction (RVEF) were calculated for each patient. F.u. scans were similarly analyzed, if available.2, p=0.028) and LVEF improved from 56% to 66% (p=0.028); in NFM LVEDVi and LVEF were unchanged at f.u. . F.u. LVEF and RVEF did not differ significantly between FM and NFM, 66% (60-69) vs 65% (61-69), p=0.79 and 62% (57-68) vs 63% (59-68),p=0.69 respectively. In both FM and NFM LVmi significantly decreased from baseline . There was a trend towards a more pronounced reduction of LVmi in FM, but the difference fell short of statistical significance .Four pts with FM died and 3 were heart transplanted before performing CMR and thus were excluded from the analysis; none of the pts with NFM died or were transplanted before CMR. In total, 68 pts  were included: 11 (16%) with FM and 57 (84%) with NFM underwent CMR. Baseline scans were obtained earlier in the NFM group, 5 (3-9) vs 12 (7-21) days after presentation, p = 0.0035. Baseline LVEF was significantly lower in FM compared to NFM, 56% (43-65) vs 64% (59-68),p=0.026. RVEF was lower in FM than in NFM pts, 56% (52-58) vs 63% (58-66),p=0.0024. F.u. scans were available in 47 pts  and were obtained after a median of 169 (110-203) days from baseline scan in FM and 148 (93-242) days in NFM (p=0.78). In FM, LVEDVi was increased at f.u. (from 75 to 77 mL/mPts with FM achieved normal LVEF at f.u., despite a lower baseline LVEF, even if a mild LV remodeling was observed at f.u. This might in part be due to a more pronounced decrease in LVmi, likely secondary to more severe myocardial edema in FM, but this observation warrants further investigation and longer f.u. to better understand long term consequences of FM on ventricular remodeling and prognosis.


The potential mechanisms underlying diastolic dysfunction and heart failure caused by these cTnI C-terminal mutations are discussed as well. Furthermore, calcium desensitizing in correction of impaired relaxation in myocardial cells due to cTnI mutations is discussed. Finally, we describe a model of translational study, i.e., from bedside to bench and from bench to bedside. These studies may enrich our understanding of the mechanism underlying inherited cardiomyopathies and provide the clues to search for target-oriented medication aiming at the treatment of diastolic dysfunction and heart failure.Cardiac troponin I (cTnI) plays a critical role in regulation of cardiac function. Studies have shown that the deficiency of cTnI or mutations in cTnI (particularly in the C-terminus of cTnI) results in diastolic dysfunction (impaired relaxation) due to an increased myofibril sensitivity to calcium. The first clinical study revealing the association between restrictive cardiomyopathy (RCM) with cardiac troponin mutations was reported in 2003. In order to illustrate the mechanisms underlying the cTnI mutation caused cardiomyopathy, we have generated a cTnI gene knockout mouse model and transgenic mouse lines with the reported point mutations in cTnI C-terminus. In this paper, we summarize our studies using these animal models from our laboratory and the other  The former contains mainly myosin and myosin bind C-protein and the latter contains actin and troponin-tropomyosin complex. The so called cross-bridge formation between the thin filament actin and the thick filament myosin determines the filament movement, i.e., muscle contraction and relaxation. Whereas, the troponin complex plays an important role in regulation of the filament movement. Troponin complex consists of three subunit proteins: Troponin C (TnC), troponin T (TnT), and troponin I (TnI). Among them, TnC is a Ca2+ concentration results in an enhanced cardiac contractility whereas the decreased Ca2+ concentration can reduce the cardiac contractility. The concentration of intracellular Ca2+ is regulated by various calcium handling proteins in myocardium, such as Ca2+ channel receptors, the SERCA2a calcium ATPase pump, phospholamban, etc. , dilated cardiomyopathy (DCM), and restrictive cardiomyopathy (RCM)  was in 2003  modeling human RCM mutation cTnI R192H (cTnI R193H in mouse sequence) in the heart. In addition, our laboratory has created another TG mouse line containing the RCM cTnI K178E mutation reported by Mogensen et al.  mice  expressing human RCM mutation cTnI R192H (cTnI R193H in mouse sequence) in the heart. Histological examination confirms that cTnI193His mice do not show cardiac hypertrophy or ventricular dilation. The general morphology of the ventricles from these mice is similar to that of a wild type heart. However, the enlargement of bi-atria, both right and left atria, is very dramatic, which is similar to that in human RCM patients carrying cTnI R192H mutation. Functional measurements on these mice indicate a diastolic dysfunction in the early stage and a diastolic heart failure in the late stage  that expresses the cTnI with N-terminal deleted in the heart, we discovered that the hyposensitivity caused by cTnI-ND favored a general balance of myofibril sensitivity to calcium in the heart and reversed the diastolic dysfunction and rescued RCM phenotype  may alter myofilament sensitivity to Ca2+ via their inhibitory effect on actomyosin cross-bridge formation -epigallocatechin-3-gallate (EGCg) has Ca2+ desensitizing abilities via its interaction with cTnC (Liou et al., 2+ by forming a ternary complex with the C-terminal domain of troponin C and the anchoring region of cTnI (Liou et al., 2+ is reduced as a result which facilitates cardiac relaxation (Liou et al., 2+ hypersensitivity and diastolic dysfunction has been demonstrated in a HCM mouse model confirming the therapeutic potential of that compound for diastolic dysfunction (Tadano et al., Increased Ca193His RCM mice (Li et al., In our recent study, we have reported that diastolic dysfunction is corrected in RCM mice after the treatment of EGCg for 3months, suggesting that desensitizer catechin extracted from green tea is helpful in correcting impaired relaxation caused by calcium hypersensitivity in cTnICardiac troponin plays a critical role in cardiac contraction and relaxation. cTnI deficiency or mutations are associated with RCM characterized with a diastolic dysfunction. The discovery of sarcomeric protein mutations responsible for the development of the disease helps in identifying the etiology of RCM and allows for the screening of potential RCM patients. These measures may facilitate early diagnostic of the disease and proper monitoring and management of RCM patients. It also paves the way for the development of transgenic animals with the RCM phenotype which will contribute greatly to a better understanding and characterization of the disease. In fact, RCM transgenic animals may provide a link in the translational study which is from bedside to bench and from bench to bedside. They will also be very useful for the trial of potential drugs or devices designed to correct the diastolic dysfunction associated with RCM. The lack of effective treatments and the unavailability of drugs that selectively correct the diastolic dysfunction of the restricted heart, make the development of new pharmacological agents an urgent necessity. Desensitizing green tea extract catechin has been proved to be useful in correcting hypersensitivity and reversing diastolic dysfunction both in RCM animal studies and in reconstitute myofilament assays using a cTnI with a point mutation from HCM patient. It seems promising to apply desensitizing green tea extract catechin in correcting impaired relaxation in RCM patients caused by troponin mutations.XL, DP, JZ, CN, WS, and XH participated in paper writing and LZ, JQ, and JT participated in patient sample collection and genotyping measurements.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Peak systolic KE/SV did not differ in patients compared to the LV in controls . Peak diastolic KE/SV in Fontan patients was lower than in the LV of the control group . The KE during diastole showed a plateau in patients with aortopulmonary collaterals. This is to our knowledge the first study that quantifies the intraventricular KE of Fontan patients. KE is dependent on the morphology of the ventricle, and diastolic KE indexed to SV in patients is decreased compared to controls. The lower KE in Fontan patients may be a result of impaired ventricular filling.Four-dimensional (4D) flow magnetic resonance imaging (MRI) enables quantification of kinetic energy (KE) in intraventricular blood flow. This provides a novel way to understand the cardiovascular physiology of the Fontan circulation. In this study, we aimed to quantify the KE in functional single ventricles. 4D flow MRI was acquired in eleven patients with Fontan circulation  and eight healthy volunteers . Follow-up MRI after surgical or percutaneous intervention was performed in 3 patients. Intraventricular KE was calculated throughout the cardiac cycle and indexed to stroke volume (SV). The systolic/diastolic ratio of KE in Fontan patients was similar to the ratio of the controls’ left ventricle (LV) or right ventricle (RV) depending on the patients’ ventricular morphology (Cohen´s The online version of this article (doi:10.1007/s00246-016-1565-6) contains supplementary material, which is available to authorized users. The Fontan operation is the procedure of choice used to palliate patients with a congenital heart defect not suited for biventricular repair . One funThe Fontan circulation is dependent on an elevated systemic venous pressure, low pulmonary vascular resistance, and low left atrial pressure , 3. The Studies show decrease in survival beyond 15–20 years after surgery in Fontan patients  and the The ability of the ventricle to deliver cardiac output to the body is facilitated by the looped shape anatomy of a morphological left ventricle that helps to conserve the momentum of blood  through Therefore, the aim of this study was to noninvasively quantify the kinetic energy during the entire cardiac cycle of the single ventricle in Fontan patients using four-dimensional phase-contrast magnetic resonance imaging (4D PC-MRI) to better understand the circulation and the pathophysiology of complications.Patients with Fontan circulation referred to Skane University Hospital for a cardiovascular magnetic resonance (CMR) examination were prospectively included. The inclusion time was from November 2013 until September 2014. In addition to routine clinical examination, 4D flow was acquired. Eight healthy volunteers  were used as controls. Healthy controls were recruited by advertising at the local institution and had to have blood pressure <140/90, normal ECG, no cardiovascular medication, and no medical history of cardiovascular or other systemic disease to be included. The Fontan KE was compared on a group level to the LV KE of controls. The reason for comparing with the LV was that even if there is an RV morphology in a Fontan patient, the systemic ventricle is pumping with the requirements closer to an LV rather than an RV.The principles of the Helsinki declaration were followed and the study was approved by the Regional Ethical Review Board, Lund, Sweden. Written informed consent was obtained from all subjects or their parents if <18 years of age.4D PC-MRI flow acquisitions and cine images were acquired as previously described and validated in vivo and in vitro , 25. In A steady-state free precession sequence  was used to collect cine images covering the entire heart. Flow measurements with a phase-contrast velocity mapping fast field echo sequence (TR/TE/flip angle: 10 ms/6.5 ms/15° in-plane resolution 1.2 × 1.2 mm) during free breathing as earlier described and validated were performed in the ascending aorta to measure the effective stroke volume (SV) and cardiac index (CI) .Gadolinium contrast is not required for the 4D flow acquisitions and was not given as part of the study protocol but was administered in 2/11 patients due to clinical questions of myocardial fibrosis in one case and MR angiography in one case.http://segment.heiberg.se), using an in-house developed module for 4D PC-MRI analysis of KE [Images were analyzed with the Segment software , the tunnel or conduit from the inferior vena cava (IVC), and the pulmonary artery (PA) branches were manually traced in all phases of the cine images. The segmentation was imported to the reconstructed 4D flow dataset with manual correction when needed. KE was calculated within the resulting delineation of the ventricle throughout the cardiac cycle in the 4D flow images. The KE of a voxel was calculated as KE=½05 g/cm3 . The KE http://fourflow.heiberg.se) enabling anatomical correlation of KE. Peak systolic and diastolic velocities were quantified in the outflow and inflow of the ventricles, and correlated to systolic and diastolic peak KE, respectively. The electronic supplement file Movie 1 shows step by step how KE was analyzed using 4D flow MRI.The location of the KE in the ventricle was performed by exporting velocity data and anatomical images from Segment to the open-source 4D flow software FourFlow  were evaluated during catheterization using fluoroscopic angiography of the thoracic aorta and the degree of collateral flow from MRI. APC blood flow was calculated using MRI by subtracting the flow volume in the caval veins from the aortic flow measured by 2D flow. The difference between pulmonary and caval venous flows was used for APC quantification in three patients where aortic flow measurements were not available . Seven oStatistical analysis was performed using GraphPad . Ventricular KE is presented as means ± SD. Differences in KE between Fontan patients and healthy volunteer groups were assessed using the Mann–Whitney test.Since the number of patients in each group was small, statistical comparisons were not performed for differences between subgroups.Cohen´s kappa was analyzed for the relation of KE pattern and ventricular morphology.Eleven patients with Fontan circulation underwent 4D PC-MRI. One example of intracardiac and cavopulmonary blood flow is shown in Movie 2 in electronic supplements. The patients’ characteristics are shown in Table Five clinically stable patients  and 6 patients  who had complications were included in the study. Six patients had complications with need of intervention for pulmonary branch stenosis in four cases, restrictive atrial communication in one case, and severe APC in one case. Three patients underwent a follow-up MRI after surgical or percutaneous intervention. The interventions are described in Table n = 4) had a lower systolic KE peak and a relatively higher diastolic peak (systole/diastole <1). Patients with right ventricular morphology and a long outflow tract (n = 6) had a higher systolic than diastolic peak (systole/diastole >1). One patient, number 11, had a morphological left ventricle (LV) where the blood had to pass through a VSD via small RV to the aorta. A high diastolic peak, but even higher systolic peak, was seen in this patient (systole/diastole >1). Visualization showed that the KE in systole was mainly located in the outflow tract and during diastole from the mitral valve into the ventricle. KE in one patient is visualized as an example in Fig. In all Fontan patients, two KE peaks were seen, one in systole and one in diastole. The KE throughout the cardiac cycle or the KE patterns is shown in Fig. n = 11) compared to the LV in controls , peak systolic , and peak diastolic values . There were no correlations between peak systolic velocity and peak systolic KE  or peak diastolic velocity and peak diastolic KE .No correlation was seen between ejection fraction and KE/SV regarding mean ; and in controls r = 0.7; p = 0.05 for EDV and r = 0.8; p = 0.02 for ESV.There was a significant correlation between mean KE and ventricular volumes in both patients and controls. In patients, The KE patterns in patients after intervention compared to baseline MRI are shown in Fig. Interobserver variability for EDV was − 1 ± 12%.n = 11) was 0.0058 ± 0.0045 mJ/ml; in SVC (n = 10) 0.0093 ± 0.0023 mJ/ml; in left PA (n = 8) 0.018 ± 0.009; and in right PA (n = 8) 0.015 ± 0.006 mJ/ml. In 5/11 patients, KE could be quantified in SVC, the tunnel/conduit from the IVC, and both PA branches. In this subgroup, the mean KE was significantly higher in both PA branches together, 0.034 ± 0.006, than in the tunnel/conduit + SVC, 0.014 ± 0.006 (p = 0.008). The mean cross-sectional area of both PA branches together was 2.2 ± 1.2 cm2 and in the tunnel/conduit + SVC 4.4 ± 0.9 cm2.KE in the tunnel or conduit from IVC could be quantified in all the patients. KE could not be analyzed in both PA branches in all patients and in one case in SVC due to stent artifacts or too short vessel. Mean KE in the tunnel/conduit . The interventricular difference of the LV as a pressure pump and the RV as a volume pump  is refleThe study also shows that peak diastolic KE/SV is lower in patients with Fontan circulation compared to controls. These findings differ from results in adult heart failure patients  where diThe high correlation between KE and ventricular volumes is explained by the fact that KE is calculated from both velocity and mass of the blood. The large differences in size and heart rates in the study population were the reason to index KE to stroke volume (SV). SV was chosen as more appropriate compared to ventricular volumes as EDV differs greatly with the type of heart defect in Fontan patients. Stroke volume is the net result of ventricular filling and contraction and as such intuitive for indexing. Another way to index could be to body surface area as in, for example, Jeong et al.´s article on patients with tetralogy of Fallot . KineticThree patients in this study underwent a second examination after surgical or percutaneous intervention. The results show remarkably similar magnitude and basic pattern of KE over the cardiac cycle at the two examinations. This suggests that the KE pattern is quite specific to each patient. A possible explanation to the change in diastolic curve shape after intervention in patient 6 could be that the aortopulmonary collaterals before intervention caused an extra inflow with high pressure in the atrium leading to a plateau of the KE curve during diastole. This explanation is supported by the fact that all patients in this study who had clinically significant aortopulmonary collaterals (APCs) also had a plateau in the diastolic part of the KE curve. The rise in diastolic KE in patient 4 after surgery might reflect an increase in pulmonary arteriovenous fistulas coherent with the clinical picture. These results address the complexity in evaluating KE in patients with Fontan circulation and indicate that the clinical implication for using KE in this patient group primarily is to better understand the physiology and to follow the patients on an individual basis. In our study, only one patient had fenestration between the conduit and the atria. The possible effects on ventricular KE from flow through the fenestration are not known but it may be similar to APC with a diastolic plateau and higher KE in diastole if the fenestration causes higher preload. In one of the patients in whom no significant APC could be identified, there was a diastolic plateau. Larger numbers of Fontan patients with KE are needed to see if the diastolic plateau pattern is related to other clinical parameters than APC flow. Recently, Schiavazzi et al. used modeling to calculate the effects of left pulmonary artery stenosis on hemodynamics in single ventricles stage II surgery and found that the stenosis needed to be quite severe, >65% of the diameter, to be hemodynamically significant . This isThe analysis of KE indexed for stroke volume in the Fontan pathway showed a significant increase in KE from the caval veins to the PA branches. This is probably explained by the smaller cross-sectional area of the PA branches compared to the caval veins.Another way to analyze KE in the ventricle is to divide it based on whether the volume goes directly from the atria to the aorta in the same heart beat or if it stays one or more heart beats in the ventricle . ErikssoA study of kinetic energy in patients with Tetralogy of Fallot, recently published by Jeong et al , shows tIn Fontan patients, breathing contributes to the return of blood to the lungs to a higher extent than in normal physiology . Therefon = 1) was also under anesthesia at the post-intervention CMR. Heart rates varied between examinations, but indexed KE remained similar independent of heart rate. There may be age-related differences in KE and in this study we did not have age matched controls. However, this was compensated for by indexing KE to SV.The study population is small and therefore statistical comparisons of the subgroups of left and right ventricular morphology and patients before and after intervention could not be made. Conclusions of the effect on KE of APC’s or interventions are also limited by the small sample size, but the data presented can point to applications where future studies may provide insights of Fontan physiology. In the Fontan group, five out of eleven patients were ventilated during the examination and this may affect the results. However, the KE results from the ventilated patients do not appear different from the nonventilated patients, but this needs to be further investigated. The patient who was under anesthesia pre-intervention Movie 2. Movie showing an example of intracardiac and cavopulmonary blood flow in a patient with Fontan circulation. (MP4 4104 KB)


Recognise the diagnosis of tachycardiomyopathy (TCMP)Understand the pathophysiologyDetermine treatment strategies to restore left ventricular functionThe role of TCMP in non-responders to cardiac resynchronisation‘Atrial and/or ventricular dysfunction—secondary to rapid and/or asynchronous/irregular myocardial contraction, partially or completely reversed after treatment of the causative arrhythmia’arrhythmia-induced), and another where the arrhythmia exacerbates ventricular dysfunction and/or worsens heart failure (HF) in a patient with concomitant heart disease (arrhythmia-mediated).Tachycardiomyopathies (TCMP) are an important cause of left ventricular (LV) dysfunction that should be recognised by physicians as they are potentially reversible and have a significant impact on morbidity and prognosis. They are classically defined as the reversible impairment of ventricular function induced by persistent arrhythmia. However, it is becoming increasingly evident that they can be induced by atrial and ventricular ectopy promoting dyssynchrony and indeed the term ‘arrhythmia-induced cardiomyopathy’ is emerging to describe the phenomenon.primary tachycardia, which makes TCMP important to identify and treat promptly.The mechanisms of TCMP are not fully defined but include subclinical ischaemia, abnormalities in energy metabolism, redox stress and calcium overload.A timely diagnosis of TCMP is important given the potential for recovery with appropriate treatment. The possibility of TCMP should be considered when eliciting a history of any new diagnosis of LV dysfunction, if there is evidence of persistent or frequently occurring tachycardia or frequent premature ventricular complexes (PVCs).It has been suggested that chronic tachycardia that occurs >10%–15% of the day may result in cardiomyopathy.However, as explained above, in the case of atrial fibrillation (AF) or PVCs, it is not only a high heart rate (HR), but also asynchronous myocardial contraction, that can lead to LV dysfunction.The resting HR may not give an indication of the mean HR, as there may be an exaggerated response to exertion, so ambulatory monitoring is important for diagnosis as well as identifying subclinical arrhythmias.Other factors that point to a diagnosis of TCMP include: (i) evidence of a previously normal ejection fraction (EF) and a degree of LV dysfunction out of proportion to other comorbidities, (ii) no other cause of non-ischaemic cardiomyopathy found , (iii) absence of left ventricular hypertrophy, (iv) relatively normal LV dimensions (LV end-diastolic dimension below 5.5 cm), (v) recovery of LV function after control of tachycardia  and (vi) rapid decline in LV ejection fraction (LVEF) following recurrence of tachycardia in a patient with recovered LV function after previous control of tachycardia.While the classic definition of TCMP refers to an impairment of LV function in the absence of structural heart disease, in practice patients with pre-existing ventricular dysfunction often deteriorate in the face of an uncontrolled tachycardia, and therefore the role of the tachycardia should be taken into account. It may be difficult in such circumstances to distinguish whether the arrhythmia or the cardiomyopathy is the primary driver. Cardiac imaging provides important information in TCMP to identify underlying structural disease—patients initially have smaller LV end-diastolic diameters and LV volume adjusted for body surface area and LV mass compared with patients with idiopathic dilated cardiomyopathy.Serial assessment of the N-terminal pro-B-type natriuretic peptide (NT-proBNP) ratio (NT-BNP at baseline/NT-BNP during follow-up) can differentiate TCMP from irreversible dilated cardiomyopathy. A prompt decline in NT-proBNP levels, after direct currect (DC) cardioversion of AF was associated with reversible cardiomyopathy with an accuracy of 90% in one series.The diagnosis of TCMP may be evident only after restoration and maintenance of sinus rhythm, or after aggressive rate control meaning a two-pronged approach to treat the arrhythmia and cardiac dysfunction is required.Once the diagnosis of TCMP has been made, many authors advocate a pro-active treatment approach. The exact strategy employed is dependent on the causative arrhythmia, as detailed below, where either a rate or rhythm control strategy may be more appropriate.The first report of a man with dilated cardiomyopathy resulting from rapid AF was by Gossage in 1913.10.1136/heartjnl-2016-310391.supp1Supplementary file 110.1136/heartjnl-2016-310391.supp2Supplementary file 2et alWhipple Randomised studies of AF ablation do demonstrate positive effects on LV remodelling once sinus rhythm is re-established over and above pure rate control. Restoration of sinus rhythm with pulmonary vein isolation was superior to AV node ablation and cardiac resynchronisation (CRT), where the effects of single chamber VVI pacing are minimised .36 37 InThis highlights that restoration of sinus rhythm is an important determinant of recovery of LV function if it can be achieved long term. The patients most likely to respond to this ‘rhythm control’ ablation approach are those with no evidence of myocardial abnormalities on advanced imaging and an otherwise normal ECG without significant conduction/repolarisation changes. Patients with a short history of symptoms coinciding with the onset of AF appear to have the highest chance of success using this approach, although large randomised controlled trials are required to address this formally with prolonged follow-up, for example, Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation (CABANA) and Early Treatment of Atrial Fibrillation for Stroke Prevention (EAST) trials. Once advanced structural remodelling in the atria has occurred (significant LA dilation), the chances of long-term ablation success decline.Atrial flutter is another common cause of TCMP. One study found that there was LV dysfunction in 25% of patients presenting in atrial flutter, and 57% of cases improved after ablation.Re-entrant SVTs including atrioventricular nodal reentrant tachycardia (AVNRT) and  atrioventricular reentrant tachycardia (AVRT) are usually paroxysmal and are therefore a rare cause of TCMP.A non-re-entrant form of AV nodal tachycardia may occasionally cause TCMP when a single sinus beat leads to two ventricular depolarisations with simultaneous antegrade conduction through fast and slow AV nodal pathways.Ventricular arrhythmias causing TCMP are generally idiopathic in nature, as otherwise they may be classified as being part of the disease process leading to both arrhythmias and LV dysfunction. Thus, sustained monomorphic VT rarely causes TCMP, as it is more often associated with pre-existing structural heart disease. Idiopathic VT, if persistent or sufficiently frequent, may result in reversible LV dysfunction.Another area of much investigation and debate is the role of PVCs in promoting LV dysfunction. This issue has been addressed by several studies examining PVC burden and the role of ablation with LV impairment ranging from PVC frequency thresholds of 5–30 000 beats in 24 hours.The question of whether to ablate asymptomatic monomorphic PVCs when the burden is high should be discussed carefully with the patient as PVC ablation particularly in the right ventricular outflow tract does carry a small but important risk of tamponade (<1%) and even death. Since PVC ablation restores normal LV function in the structurally normal heart, a pragmatic approach in these cases is simply to monitor the patient for signs of LV impairment and only consider ablation should this be the case. This is because isolated PVCs have an excellent prognosis in the normal hearts with preserved function anyway, so there is no reason to intervene unless significant dysfunction develops. Recently, Bhushan and Asirvatham have proposed criteria regarding PVC-induced cardiomyopathy. They suggest that otherwise young healthy individuals, without abnormal cardiovascular substrate having over 20 000 PVCs per day, no more than two PVC morphologies, PVCs originating from outflow tracts or from the fascicles and with preserved myocardial wall thickness are the best candidates for presumption of a PVC-induced cardiomyopathy diagnosis.The role of PVCs in promoting LV impairment is becoming evident in determining the response to CRT.The time course of TCMP has mostly been studied in animal models with rapid pacing. Haemodynamic abnormalities may be seen 24 hours after the onset of rapid pacing. After 1 week, there will be increased filling pressures, increased pulmonary artery pressures and decreased systemic arterial pressures. Up to 3–5 weeks, the cardiac output, EF, cardiac volume continue to worsen.Similarly in humans, there is usually rapid clinical improvement. By 3 months after successful treatment of tachycardia whether by rhythm or rate control, nearly complete recovery of symptoms and LV contractility is generally observed.There is evidence to suggest that recurrent tachycardia in patients who have previously had TCMP, may result in a faster and more severe onset of TCMP than the initial presentation. In one study of 24 patients with TCMP, 5 had recurrent tachycardia associated with a rapid drop in EF and symptoms of clinical HF occurring within 6 monthsThere is very little information available regarding the risk of sudden death in TCMP. HF, whatever the aetiology, leads to an arrhythmogenic substrate with repolarisation abnormalities implicated in leading to ventricular arrhythmias. Most studies have employed animal models, which have given conflicting results. A porcine model shows prolonged repolarisation, but with no deathsA contentious issue is whether patients with resolved TCMP and normal LV function continue to have increased risk of lethal arrhythmia due to pathological remodelling. Evidence is scarce, with one case report of three patients with AF-related TCMP where EF had normalised with treatment. They all died suddenly months to years later, with normal EF and no symptoms of HF or recurrent tachycardia.Although the aetiology of TCMP is well defined, there remain a number of unanswered questions in terms of identifying patients most at risk and the timing of any intervention. Furthermore, there may be specific genetic, molecular and structural features which identify patients at greatest risk that require further investigation. Also a proportion of patients do not necessarily fully respond to rhythm control or remain at risk of lethal arrhythmia. Identification of specific biomarkers to identify these individuals should be pursued through genetic, molecular profiling and imaging strategies.There is a wide range of causative arrhythmias, clinical presentations and natural histories for TCMP. The diagnosis of TCMP is difficult and a high index of suspicion is required. Given the potential for recovery with appropriate treatment, a proactive approach is recommended, whether that be rate or rhythm control. With advances in cardiac imaging and ablation techniques, it may be possible to identify patients with reversible causes of cardiomyopathy early in the disease process with those most likely to respond to rhythm control. In the meantime, a strategy attempting to minimise arrhythmia burden to assess the response even if short term, for example, DC cardioversion for AF with anti-arrhythmic therapy gives a pragmatic approach to identify such cases.Always consider an arrhythmic aetiology as a factor contributing to cardiac dysfunction, especially in the absence of overt ventricular structural abnormalities.Seriously consider an early rhythm control strategy and the possibility of ablation in atrial fibrillation cases with tachycardiomyopathy.Carefully review ventricular ectopic burden and morphology in cardiomyopathy cases with a view to electrophysiological assessment for ablation.Consider ablation of monomorphic ectopics in cardiac resynchronisation non-responders if receiving <97% biventricular pacing due to ventricular ectopy.Education in Heart articles are accredited for CME by various providers. To answer the accompanying multiple choice questions (MCQs) and obtain your credits, click on the 'Take the Test' link on the online version of the article. The MCQs are hosted on BMJ Learning. All users must complete a one-time registration on BMJ Learning and subsequently log in on every visit using their username and password to access modules and their CME record. Accreditation is only valid for 2 years from the date of publication. Printable CME certificates are available to users that achieve the minimum pass mark.


Late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) is a widely used clinical method to detect fibrosis, however, its spatial resolution is limited. The purpose of this feasibility study is to determine the value of T1 mapping (Siemens prototype sequence) on a clinical 1.5T scanner . T1 mapping was performed with a modified look-locker inversion-recovery (MOLLI) sequence acquired during breath hold in the same planes after LGE imaging. Typical imaging parameters were: non-selective inversion pulse, steady-state free precession single-shot read out in mid-diastole, FOV of 360 × 250 mm2, matrix of 192 × 150, slice thickness of 8 mm, TR/TE of 375.28/1.01 ms, minimum inversion time of 90 ms, inversion time increment of 80 ms, FA of 35?, PAT factor of 2, number of inversions 2, images acquired after first inversion 3, pause 3 heart beats, and images acquired after second inversion. T1 Mapping was used for measurement of T1 values. Global ECV values were calculated from T1 maps acquired pre- and post-contrast calibrated by blood hematocrit. The extracellular volume (ECV) value was calculated as: ECV = (1-hematocrit) (1/T1myopost-1/T1myopre) / (1/T1bloodpost-1/T1bloodpre).Thirty HCM patients and 20 healthy volunteers underwent conventional late gadolinium enhancement (LGE) imaging and T1 time and myocardial ECV in patients with HCM was significantly higher than the measurement in control cases, and post-contrast myocardial T1 time in HCM patients was significantly lower than that in control cases  . Pre-contrast myocardial T1 mapping used in the present study has combined the fast acquisition time and multiple contrast capabilities of the TI scout with the improved CNR, spatial resolution, and spatial coverage of the segmented IR LGE scans. The combination reduces the total imaging time, enables T1 quantification, and does not compromise image quality. A relatively higher pre-contrast T1 value and ECV, and lower post-contrast T1 value were found with T1 mapping in the myocardium of HCM patients, which suggested T1 mapping is better in the evaluation of myocardial fibrosis. The main limitation is that we had a small patient population without subgroup analysis and follow-up.The MOLLI T