T1 mapping enables assessment of myocardial characteristics. As the most common type of arrhythmia, atrial fibrillation (AF) is often accompanied by a variety of cardiac pathologies, whereby the irregular and usually rapid ventricle rate of AF may cause inaccurate T1 estimation due to mis-triggering and inadequate magnetization recovery. We hypothesized that systolic T1 mapping with a heart-rate-dependent (HRD) pulse sequence scheme may overcome this issue.30 patients with AF and 13 healthy volunteers were enrolled and underwent cardiovascular magnetic resonance (CMR) at 3 T. CMR was repeated for 3 patients after electric cardioversion and for 2 volunteers after lowering heart rate (HR). A Modified Look-Locker Inversion Recovery (MOLLI) sequence was acquired before and 15 min after administration of 0.1 mmol/kg gadopentetate dimeglumine. For AF patients, both the fixed 5(3)3/4(1)3(1)2 and the HRD sampling scheme were performed at diastole and systole, respectively. The HRD pulse sequence sampling scheme was 5(n)3/4(n)3(n)2, where n was determined by the heart rate to ensure adequate magnetization recovery. Image quality of T1 maps was assessed. T1 times were measured in myocardium and blood. Extracellular volume fraction (ECV) was calculated.st fixed sampling scheme were smaller than from the 1st HRD and 2nd fixed sampling scheme. In healthy volunteers, the overall native T1 times and ECV of the left ventricle (LV) in diastolic T1 maps were greater than in systolic T1 maps . In the 3 AF patients that had received electrical cardioversion therapy, the myocardial native T1 times and ECV generated from the fixed sampling scheme were smaller than in the 1st and 2nd HRD sampling scheme . In patients with AF , more T1 maps with artifact were found in diastole than in systole (P < 0.01). The overall native T1 times and ECV of the left ventricle (LV) in diastolic T1 maps were greater than systolic T1 maps, either with fixed or HRD sampling scheme .In volunteers with repeated T1 mapping, the myocardial native T1 and ECV generated from the 1Systolic MOLLI T1 mapping with heart-rate-dependent pulse sequence scheme can improve image quality and avoid T1 underestimation. It is feasible and with further validation may extend clinical applicability of T1 mapping to patients with atrial fibrillation. Atrial fibrillation (AF) is the most common clinical cardiac arrhythmia. The mechanisms of AF are complex and associated with structural and electrical remodeling in the atrial and ventricular myocardium . DevelopTherefore, we hypothesize that systolic T1 mapping with heart-rate-dependent (HRD) pulse sequence sampling scheme may be feasible in patients with AF. We compared the differences of T1 times and ECV acquired in systolic and diastolic phase with fixed/HRD pulse sequence sampling scheme, and assessed the accuracy of systolic T1 mapping with HRD pulse sequence sampling scheme in patients with AF who underwent cardiovascular magnetic resonance (CMR) twice, before and after electric cardioversion.The study was approved by Beijing Anzhen Hospital ethics committee, and written informed consent was obtained from all participants. A detailed explanation concerning contrast agent was given to each participant.2).Thirteen healthy volunteers and thirty patients with “persistent” AF without contraindication to CMR were recruited. None of the healthy volunteers was referred as patient for clinical CMR which then turned out to be normal, all of them had no evidence or risk factors of cardiovascular disease. The AF patients were defined as “persistent”, whose duration of continuous AF episodes lasted > 7 days or required electrical cardioversion. Exclusion criteria were presence of a permanent pacemaker, severe claustrophobia, and severe impairment of renal function 3 or 4(1)3(1), the inversion time between data acquisition is fixed as 3 heartbeats or 1 heartbeat as shown in the parentheses. At higher heart rate, each single heartbeat duration is shorter than at slow heart rate. Under such circumstances, the shorter inversion time will lead to inadequate magnetization recovery before acquiring the next data inversion episode, which results in underestimation of T1 times. To ensure the full recovery of longitudinal magnetization before the following inversion pulse is applied, the following pause in units of heartbeats needs to be increased along with the increase of the heart rate. Theoretically, after a duration of 4 times of T1 time , the magnetization of tissue is almost back to equilibrium. For the 5(3)3 scheme, at heart rate of 60 beats per minute , it takes (5 + 3) × 1000 = 8000 ms  until the second inversion is played out. At higher heart rate, using the above scheme may lead to inadequate inversion recovery. It would make sense to set up different sampling schemes that adapt to the increased heart rate.For the consideration of ensuring complete magnetization recovery at higher heart rates, the sampling schemes 5(3)3 and 4(1)3(1)2 were adopted to modify the recovery to be determined by heart rate. Based on the principle that 5(3)3 scheme is optimized for a heart rate of 60 bpm (1000 ms), for the pre-contrast T1 mapping, the heartbeat number of the second T1 inversion recovery is calculated as: n = (5+3)/(heart rate in ms) × 1000-5; for the post-contrast T1 mapping, the heartbeat number of the inversion is calculated as: n = (4+1)/(heart rate in ms) × 1000-4. We set up sampling schemes for various heart rate ranges with bpm increment of 5 from 50 to 150 bpm Fig. .Fig. 1FlFor the purpose of testing the feasibility and accuracy of T1 mapping with the HRD pulse sequence sampling scheme, two healthy volunteers in normal sinus rhythm with relatively high heart rate  during first scan were asked to undergo two CMRs before and after taking beta-blockers. They underwent T1 mapping with fixed and HRD sampling scheme at first scan, and at the next day, after taking beta-blocker, they underwent the second T1 mapping scan with fixed sampling scheme . The left-ventricle myocardial per-segment native T1 time and ECV generated from fixed sampling scheme at first scan, HRD sampling scheme at first scan, and fixed sampling scheme at second scan were compared.For observing the impact of different cardiac phases (systole and diastole) on T1 times, 11 healthy volunteers in normal sinus rhythm  underwent T1 mapping with fixed sampling scheme (5(3)3/4(1)3(1)2) at diastole and systole. The number of T1 maps and myocardial segments with artifact generated from different cardiac phases were recorded and compared; the T1 time and ECV generated from different cardiac phases were compared.For verifying the feasibility of systolic T1 mapping with HRD sampling scheme, patients with AF  underwent T1 mapping with fixed and HRD sampling scheme at diastole and systole. The number of T1 maps and myocardial segments with artifact generated from different sampling scheme and cardiac phases combination were recorded and compared; the T1 time and ECV generated from different sampling scheme and cardiac phases combination were compared.For the purpose of verifying the accuracy and effectiveness of systolic T1 mapping with the HRD pulse sequence sampling scheme, three patients (with AF) who received electric cardioversion, at the next day of cardioversion underwent the second T1 mapping with HRD sampling scheme in sinus rhythm, at diastole and systole. The left-ventricle myocardial per-segment native T1 time and ECV generated from different sampling schemes and cardiac phases combination at first scan, and HRD sampling scheme with different cardiac phases at second scan were compared. The flow chart of study is showed in Fig. All CMR was performed using a 3 T MR system  with a 32-channel cardiac coil. Subject-specific, volume-selective first- and second-order B0-shimming based on field maps derived from double-gradient-echo acquisitions was performed to improve static field uniformity.syngo MR B17A). Data were acquired in basal, mid-ventricular, and apical short-axis planes at diastole and systole before and 15 min after administration of 0.1 mmol/kg gadopentetate dimeglumine . The diastolic phase was determined by the system with captured trigger delay (TD) according to the ECG gating, the systolic phase was set to TD of 0 ms (the acquisition started after 120 ms due to the TI start time) [2, matrix = 256 for heart rate < 90 bpm, 192 for heart rate > 90 bpm, slice thickness = 6 mm, BW= 1045-1028Hz/px, GRAPPA acceleration factor 2, linear phase-encoding ordering, minimum TI of 120 ms. The quality control was performed during scanning by reviewing the “goodness of fit” map and source images to allow an immediate repetition of suboptimal measurements to minimize the respiratory motion and off-resonance effects. The blood sample was taken just before CMR to measure hematocrit for ECV calculation.T1 mapping sequence was obtained using a Siemens prototype  . For theFor the purpose of clinical diagnosis, all patients also received CMR protocols including cine and late gadolinium enhancement (LGE) imaging as described elsewhere .All image datasets were transferred to a workstation  for offline analysis. The T1 maps and source images were assessed, myocardial segments with artifact were excluded for further analysis. Two experienced readers assessed artifacts in consensus. The heart rate of each cardiac cycle during scanning of every image was recorded, the variability in heart rate was calculated as the standard deviation from the mean heart rate.The left-ventricular (LV) myocardium was delineated by manually contouring the endo-cardial and epi-cardial borders. Care was taken to avoid contamination of signal from blood or epi-cardial fat. T1 time of the blood was measured by manually drawing a region of interest in the LV cavity of T1* map (T1 map based on fitting without Look-Locker correction) taking care to avoid the papillary muscles. When artifact existed in certain segment in image originated from any single diastole/systole and fixed/HRD sampling scheme combination, the patient’s same segment generated from T1 maps with other different cardiac phase and sampling scheme combinations were excluded for per-segment pairwise comparison. But all of the assessable segments generated from any single diastole/systole and fixed/HRD sampling scheme combination were included in calculating the respective average overall LV myocardial T1 times. The overall LV myocardial native T1 time was mean of T1 times of basal, mid-ventricular and apical levels. For the participants with repeated CMRs, all of the pre- and post-contrast per-segment  myocardial T1 times were drawn in T1 maps generated from different cardiac phases and sampling scheme combinations. ECV was calculated from T1 maps acquired pre- and post-contrast calibrated by blood hematocrit . The ECVt-test and one-way analysis of variance as appropriate. The assessable images and segments were compared between systole and diastole using χ2 test. The overall LV myocardial native T1 times and ECV generated from different cardiac phases and sampling scheme combinations were compared in all participants. The per-segment myocardial native T1 times and ECV generated from different cardiac phases and sampling scheme combinations were compared in participants with repeated CMRs. The statistical significance was defined as p < 0.05. Statistical analysis was performed using SPSS software .Data are presented as mean and standard deviation. Differences between means were tested by the paired The demographic data, heart rate and heart rate fluctuation during scan, LV functional indices of healthy volunteers and patients with AF are listed in Table st 5(3)3/4(1)3(1)2, 1st 5(4)3/4(2)3(2)2 and 2nd 5(3)3/4(1)3(1)2 either in diastolic or systolic T1 maps . In volunteer 2, there were significant differences of per-segment myocardial native T1 times and ECV between 1st 5(3)3/4(1)3(1)2 and 1st 5(7)3/4(3)3(3)2, and between 1st 5(3)3/4(1)3(1)2 and 2nd 5(3)3/4(1)3(1)2 either in diastolic or systolic T1 mappings ; but no significant differences of per-segment myocardial native T1 times and ECV between 1st 5(7)3/4(3)3(3)2 and 2nd 5(3)3/4(1)3(1)2 either in diastolic or systolic T1 mappings .For the two healthy volunteers that underwent two CMRs, volunteer 1 presented HR of 67–69 bpm during the first scan, the HRD sampling scheme was 5(4)3/4(2)3(2)2, volunteer 2 presented a HR of 86–89 bpm during the first scan with HRD sampling scheme of 5(7)3/4(3)3(3)2. In volunteer 1, there were no significant differences of per-segment myocardial native T1 times and ECV among 1χ2 = 0.204, p > 0.05).In the 11 healthy volunteers, there were 66 myocardial native T1 maps and 66 myocardial post-contrast T1 maps (11 volunteers × 3 slices × 2 (1 of diastole and 1 of systole)). 6 segments in 2 native T1 maps and 7 segments in 3 post-contrast T1 maps were excluded due to the presence of artifacts. In the native T1 maps with artifacts, 4 segments of 1 T1 map were diastolic images; in the post-contrast T1 maps with artifacts, 5 segments of 2 T1 maps were diastolic images. There were no significant differences of assessable images between systole and diastole ). 599 segments in 113 native T1 maps and 592 segments in 111 post-contrast T1 maps were excluded due to the presence of artifacts. The artifacts we encountered mainly were off resonance related dark banding artifact and mistrigger related motion artifact . Most motion artifacts were presented in patients with moderately rapid heart rate and/or with severe heart rate fluctuation  + 3 patients × 3 slices × 6 (1p < 0.05). The myocardial native T1 times generated from diastolic T1 maps were longer than systolic T1 maps either in fixed or in HRD scheme T1 maps with statistical significance , the ECV generated from diastole was larger than in systole, either in fixed or HRD sampling scheme without statistical significance . In the pre-contrast LV blood T1* maps, blood T1 times generated from diastolic phase were longer than systolic phase, while in the post-contrast LV blood T1* maps, the blood T1 times from diastolic phase were shorter than systolic phase. Regarding the comparison between fixed and HRD scheme, blood T1 times generated from fixed scheme were longer than HRD scheme in pre-contrast; In post-contrast CMR, the blood T1 from fixed scheme were shorter than HRD scheme . The LV overall native T1 times, post-contrast T1 times and ECV of myocardium, pre-/post-contrast blood T1 times generated from different diastolic/systolic and fixed/HRD scheme combination were compared and are shown in Table The myocardial native T1 times and ECV generated from HRD sampling scheme T1 maps were greater than fixed sampling scheme T1 maps either in diastolic or systolic phase with statistical significance 3/4(6)3(6)2; after electric cardioversion, the patient’s heart rate during 2nd CMR ranged 77–80 bpm, scheme was 5(5)3/4(2)3(2)2. Patient 2’s heart rate during 1st CMR ranged 64–87 bpm, HRD scheme was 5(7)3/4(3)3(3)2; the patient’s heart rate during 2nd CMR ranged 62–65 bpm, scheme was 5(4)3/4(1)3(1)2. Patient 3’s heart rate during 1st CMR ranged 80–101 bpm, HRD was 5(9)3/4(5)3(5)2; the patient’s heart rate during 2nd CMR ranged 75–77 bpm, scheme was 5(5)3/4(2)3(2)2. For all the 3 patients, either in the diastolic or systolic T1 maps, there were significant differences of per-segment native T1 times and ECV between 1st CMR fixed scheme and HRD scheme, and between 1st CMR fixed scheme and 2nd CMR HRD scheme , but no significant differences of per-segment native T1 times and ECV between 1st CMR HRD scheme and 2nd CMR HRD scheme , the differences of myocardial native T1 times and ECV between 1st fixed sampling scheme and 1st HRD/2nd CMR fixed sampling scheme reached statistical significance. In the 3 patients with AF, all the heartbeats number of T1 inversion recovery increased with a large range . The myocardial native T1 times and ECV of 1st fixed sampling scheme were smaller than 1st and 2nd HRD sampling scheme with statistical significance. The impact of the HRD sampling scheme was more prominent for higher heart rates. Thereby, HRD sampling scheme is practical for rapid ventricle rate either in sinus rhythm or arrhythmia.Incomplete inversion recovery may lead to an underestimation of T1 times. In patients with higher heart rate, the R-R interval shortened, and the fixed sampling scheme of 5(3)3/4(1)3(1)2 does not provide enough time for the magnetization to get back to the equilibrium. Increasing the number of heartbeats after T1 inversion recovery can avoid underestimation of T1 times. In our study, we tested the feasibility and accuracy of HRD sampling scheme in healthy volunteers and patients with AF with repeated CMRs. In volunteers and patients with AF, the T1 times and ECV generated from fixed sampling scheme were smaller than HRD sampling scheme, and repeated T1 mapping demonstrated that the HRD sampling scheme can more accurately estimate the T1 times than the fixed sampling scheme. In volunteer 1, the heartbeats number of T1 inversion recovery increased in a small range , although the myocardial native T1 times and ECV generated from 1In healthy volunteers and patients with AF, both for fixed and HRD sampling scheme, the myocardial native T1 times and ECV in diastole were greater than in systole. Our findings concur in general with some previous studies , 18, 19.Although apparent myocardial native T1 times and ECV in systole were smaller than in diastole, more images in systole were evaluable than in diastole. In line with other studies , 18, 20,Except the main finding of our study, our results also revealed that the myocardial native T1 times and ECV of patients with AF were greater than in healthy volunteers. The cardiac profibrotic microenvironment in AF is unlikely to be strictly limited to the atria, and the ventricular myocardium is also likely to be affected, ventricular fibrotic changes are more pronounced in AF patients than in subjects with sinus rhythm . T1 mappThe number of participants included in this study is relatively small, especially the number of participants who underwent the CMR twice. Since the repeated CMRs can test the efficiency of the HRD sampling scheme, more participants need to be enrolled in a future study. The HRD sequence used in this study is relatively old version, the inversion time is expressed as heartbeat, now a more advanced sequence with seconds as unit is widely accepted by T1 mapping research community. Due to the sequence version’s limitations, we are not able to test this sequence in our study. However, it’s suggested that we utilize this advanced version of sequence in our future study. The operation of the HRD sampling scheme is relatively complicated, and the impact of HRD sampling scheme is more prominent in higher heart rate, therefore further investigation is needed to simplify the operation under the condition of keeping the feature of HRD sampling scheme. Finally, we did not perform the intra- and inter-observer variability, although a good agreement of intra- and inter-observer variability has been demonstrated by other studies , 20.The heart-rate-dependent sampling scheme is helpful for avoiding underestimation of T1 times, especially in subjects with higher heart rates. Systolic T1 mapping yields shorter myocardial native T1 times and ECV, but the mean differences were small and, importantly, with the benefit of improvement in data quality in subjects with irregular and rapid heart rate. Together with these findings, systolic MOLLI T1 mapping with a heart-rate-dependent sampling scheme is feasible and its clinical application can be extended to patients with atrial fibrillation.


Dilated cardiomyopathy (DCM) is a leading cause of cardiac death in children. Approximately 30% of children die or need cardiac transplantation in the first year after diagnosis. We established a protocol to improve the outcome in this high-risk population.1-blocker, an angiotensin-converting enzyme inhibitor and an aldosterone antagonist. Our therapy aims to reduce oxygen consumption and improve oxygen delivery. Heart rate control is the most important goal; therefore clonidine is given after surgical procedure and digoxin in long-term treatment if heart rate remains high despite adequate β1-blocker therapy. To improve oxygen delivery our goal is to archive haemoglobin levels of 12-14 g/dl, therefore Erythropoietin is given as long term treatment. Additional treatments include supplementation of carnitine, coenzyme Q, riboflavin or thiamine.We present our experience in 21 patients  treated in our institution from 2006 to 2015. The patients were diagnosed with DCM with a highly impaired function of the LV (mean EF 17%) and a conserved function of the RV (mean EF 52%). Our protocol for medical enhancement of left ventricular recovery in association with pulmonary artery banding involves the use of a highly specific βAt a mean follow up of 36 month (range 2-120) freedom from death was 91% and freedom from heart transplantation was 85%. Surviving patients showed a significant improvement in left ventricular ejection fraction (from 17 ± 6 to 50 ± 11%) and LVEdD (z-score from +7 ± 2 to +1.7 ± 1.9). The levels of BNP improved significantly (from 3222 ± 2756 to 70 ± 56 pg/ml).Our data suggest that the medical and surgical approach described may result in a markedly improved medium-term outcome in children with DCM. Further studies are required to evaluate the long-term-outcome of these patients.


Cardiovascular Magnetic Resonance (CMR) myocardial perfusion imaging has the potential to evolve into a method allowing full quantification of myocardial blood flow (MBF) in clinical routine. Multiple quantification pathways have been proposed. However at present it remains unclear which algorithm is the most accurate. An isolated perfused, magnetic resonance (MR) compatible pig heart model allows very accurate titration of MBF and in combination with high-resolution assessment of fluorescently-labeled microspheres represents a near optimal platform for validation. We sought to investigate which algorithm is most suited to quantify myocardial perfusion by CMR at 1.5 and 3 Tesla using state of the art CMR perfusion techniques and quantification algorithms.First-pass perfusion CMR was performed in an MR compatible blood perfused pig heart model. We acquired perfusion images at physiological flow (“rest”), reduced flow (“ischaemia”) and during adenosine-induced hyperaemia (“hyperaemia”) as well as during coronary occlusion. Perfusion CMR was performed at 1.5 Tesla  and at 3 Tesla . Fluorescently-labeled microspheres and externally controlled coronary blood flow served as reference standards for comparison of different quantification strategies, namely Fermi function deconvolution (Fermi), autoregressive moving average modelling (ARMA), exponential basis deconvolution  and B-spline basis deconvolution (B-spline).All CMR derived MBF estimates significantly correlated with microsphere results. The best correlation was achieved with Fermi function deconvolution both at 1.5 Tesla  and at 3 Tesla . Fermi correlated significantly better with the microspheres than all other methods at 3 Tesla (p < 0.002). B-spline performed worse than Fermi and Exponential at 1.5 Tesla and showed the weakest correlation to microspheres . All other comparisons were not significant. At 3 Tesla exponential deconvolution performed worst .CMR derived quantitative blood flow estimates correlate with true myocardial blood flow in a controlled animal model. Amongst the different techniques, Fermi function deconvolution was the most accurate technique at both field strengths. Perfusion CMR based on Fermi function deconvolution may therefore emerge as a useful clinical tool providing accurate quantitative blood flow assessment. Coronary artery disease (CAD) related myocardial infarction (MI) and heart failure constitute a leading cause of death in the western world . MyocardWe have recently introduced a novel MR compatible explanted pig heart model that allows accurate control of regional blood flow and therefore represents an ideal vehicle for quantitative perfusion validation ,26. It iThe aim of the current study was to investigate which perfusion algorithm is most suited for quantitative analysis of perfusion CMR using this unique imaging set-up.All animal experiments were conducted after approval by the U.K. Home Office in accordance with the U.K. Animals (Scientific Procedures) Act of 1986 and in compliance with the World Medical Association Declaration of Helsinki regarding ethical conduct of research involving animals. Eight healthy Large White Cross Landrace pigs weighing between 41 and 54 kg were included in this study . Hearts were harvested as previously described ,26. SedaThe animal studies were performed on 1.5 Tesla , (n = 4) and 3 Tesla , (n = 4) clinical MR scanners. For signal reception, a clinical interventional L-flex receiver coil array was tightly positioned around the heart chamber, which was then placed in the isocenter of the magnet. Perfusion CMR data were acquired in short axis orientation of the LV following a recognized standard model .Image parameters at 1.5 Tesla were as follows: CMR-perfusion imaging was performed with a 5 fold k-t broad linear speed up technique (BLAST) accelerated balanced turbo gradient echo pulse sequence with 11 training profiles yielding a typical spatial resolution of 1.9×2×10 mm. TE/TR was 1.35/2.71; 50° flip angle; 90° prepulse and 100 ms prepulse delay.At 3 Tesla we used a saturation recovery gradient echo pulse sequence accelerated with k–t BLAST (k-t factor 5 and 11 training profiles) with a repetition time of 2.7 ms, echo time of 0.9 ms, flip angle 20°, spatial resolution at 1.3 × 1.3 × 8 mm.Perfusion-CMR was performed using a dual bolus scheme with 5 mL of dilute (0.007 mmol/mL) and 5 ml of neat (0.07 mmol/mL) gadobutrol bolus injections  . PerfusiThe LV was divided into standard segments . The SI-These quantification methods which are based on the central volume principle  deconvolCtiss(t) is related to the concentration of the contrast agent in the arterial input region Caif(t) via the following convolution equation:h(t) is the unknown tissue impulse response.According to the central volume principle the concentration of the contrast agent in the tissue region h(t) and therefore estimate the myocardial blood flow (MBF) according to h(t = 0).The above equation needs to be deconvolved to estimate Deconvolution methods used in this work are Fermi function deconvolution, (ARMA), Exponential basis deconvolution and B-spline basis deconvolution ,34.These deconvolution algorithms consist of modelling parameters and variables. The degree of splines, the number of splines and the position of the break points (control points) are the varying parameters in the B-spline function. Similarly to B-spline, the total number of exponential functions and the decay rates of the exponential functions  are the modelling parameters for exponential basis deconvolution. With ARMA, no mathematical model is used for the representation of the tissue impulse response. The auto-regressive and moving average order (Q and L respectively) are the only factors, which have influence on the model’s accuracy. The varying parameter in Fermi is a predefined parameter, which is equal to the delay time between the arrival of contrast agent at the site of the AIF, usually the LV (or the inflow tubing in the current study) and the arrival in the myocardium. This parameter which is called tOnset depends on the placement of the individual region of interest for measuring the AIF and the tissue response .It is important to note that tOnset can affect the outcome of all four deconvolution algorithms. Therefore this parameter has to be taken into special consideration when any of these methods is being used. Consequently in this study, only the intensity values after arrival of the contrast agent in the inflow tubing and myocardial tissue have been used for quantification. Effects of variation of these parameters on the outcome of deconvolution have been previously demonstrated by our group .The different algorithms and their sensitivity to changes in the underlying modelling parameters are highly affected by the quality of the data. Any perturbation can affect the accuracy of the results and introduce possible variation in the output of the process. In order to render the deconvolution process more stable, reduce the computational burden and obtain the most accurate results we used 10 time scales for exponential basis deconvolution, fourth-degree B-spline polynomial with 15 equally spaced break points ,37 and Ahttp://www.cmiss.org/cmgui). This allowed exact alignment of the upper and lower right ventricular (RV) insertion points in both images and thus precise overlay of the CMR and microsphere images . Before injection microspheres were sonicated and approximately 100,000 microspheres were diluted with whole blood to a total volume of 2 ml. Immediately after the gadolinium injection microspheres were injected into the circulation over a period of two minutes (1 ml/min injection speed) at the same site used for gadolinium injection. Up to 3 different colours of microspheres were used during the experiments. Quantitative analysis of the microtome images was performed in the same standard segments used for perfusion quantification according to previously described methods . In bries is the number of microspheres counted in a segment, Nt is the total number of microspheres injected, Ft is the total arterial input flow rate in mL/min, and Ms is the mass of a segment in grams. Segment mass was derived from segment volume, which was calculated from a fine 3D binarised left ventricular mesh. To quantify microspheres circumferentially in the same standard segments used for quantitative perfusion CMR analysis, the LV centroid and anterior RV insertion point were identified in each perfusion slice, with circumferential segments then defined every 60 degrees around the centroid allowing very accurate alignment of the respective perfusion and cryomicrotome segments . Continuous data are expressed as the mean ± standard deviation (SD). To compare quantitative perfusion measurements of the different algorithms with CMR and microspheres we used linear regression analysis and the method proposed by Bland and Altman . The FisThe paired sample t-test was used to assess the mean differences between perfusion measurements based on CMR and with microspheres. Intra-observer variability of perfusion CMR analysis was assessed using the coefficient of variation (CV) defined as the ratio of the SD to the mean of the differences between the measurements. A p-value of <0.05 was considered statistically significant. P-values of less than 0.008 remained significant after Bonferroni correction for multiple comparisons.All the explanted hearts recovered electrical function upon reperfusion. In case of reperfusion arrhythmias, defibrillation was performed to achieve sinus rhythm. Hearts were shocked for 3 ± 2 times on average. All hearts remained reasonably stable throughout the perfusion experiments. Heart Rate was 71 ± 15. The heart weight was 272 ± 19 g. The external roller pump blood flow was set to 238 ± 46 mL/min. Further measurements were taken during reduced flow at 118 ± 20 mL/min and during adenosine induced hyperemia with 392 ± 47 mL/min. These flow rates constituted an overall LV perfusion of 0.89 ± 0.18, 0.45 ± 0.1 and 1.47 ± 0.16 mL/min/g LV, respectively. On a segmental level, perfusion estimates derived from the different techniques based on CMR SI-time curves were compared to those obtained with microspheres. Figure All CMR derived MBF estimates correlated significantly with those obtained by microspheres Table . The besFermi function deconvolution correlated significantly better with the microspheres as compared to all other methods at 3 Tesla p < 0.002, Table , Table 2The Bland Altman analysis and 95% confidence intervals of the difference showed excellent results for Fermi with minimal overestimation of perfusion at 3 Tesla  at higher flow values Table . Whilst Intra-observer variability differed between algorithms. Whilst B-spline showed minimal intra-observer variability at both field strengths, the intra-observer variability of Fermi deconvolution was minimal at 1.5 Tesla and moderate to good at 3 Tesla. Exponential deconvolution showed little intra-observer variability at both field strengths whereas ARMA showed some variability at both scanners  and therefore neither CMR in the current version nor microspheres may provide absolute fully quantitative measurements. Furthermore, future work should study perfusion under fully working-heart conditions to achieve scenarios that even closer resemble in-vivo physiology to investigate the influence of different filling or working states of the heart on quantitative perfusion analysis.The current paper describes validation of different quantification algorithms based on AHA segments. Future studies will also need to determine transmural differences of perfusion from subendocardium to subepicardium and to define the diagnostic merits of such assessments at a resolution beyond the AHA segmental classification.CMR derived quantitative blood flow estimates accurately assess true myocardial blood flow in a controlled animal model. There are inherent differences between the quantification algorithms used at 1.5 Tesla and 3 Tesla. Fermi function deconvolution qualifies as the most accurate at both field strengths and may represent a technique that allows perfusion CMR quantification to develop into a useful clinical tool.


Phenylketonuria (PKU) is one of the most common inherited metabolic disorders. The molecular pathway of neurological damage is not yet sufficiently understood. To date, there is a lack information about cardiac involvement related to the disease. This study aims to characterize cardiac morphology and function in adult patients with PKU using cardiovascular magnetic resonance (CMR).28 patients with PKU (age 30 ± 9 years/mean ± SD) underwent a comprehensive CMR protocol at a 1.5T CMR scanner  including assessment of left ventricular (LV) volume and mass. In addition, T1 measurements pre- and post-administration of gadolinium for evaluation of extra corpuscular volume (ECV) and tagging for quantitative analysis of left ventricular circumferential strain (Ecc) were performed. 8 healthy age-matched volunteers underwent a similar protocol and served as controls for the ECV values. LV parameters and Ecc were compared to reference values from previous studies with similar data setup [CMR exams were successfully performed in all patients. As shown in Figure The results of this study indicate that in PKU patients compared to healthy controls LV mass indexed to BSA is reduced to the reference values; we found increased average Ecc parameters and normal ECV values. Further investigations in larger patient groups and older PKU patients are necessary for evaluation of cardiac involvement of the disease over time and its consequences.None.


Cardiac diffusion tensor imaging (cDTI) measures the magnitudes and directions of intramyocardial water diffusion. Assuming the cross-myocyte components to be constrained by the laminar microstructures of myocardium, we hypothesized that cDTI at two cardiac phases might identify any abnormalities of laminar orientation and mobility in hypertrophic cardiomyopathy (HCM).in vivo at 3 Tesla at end-systole and late diastole in 11 healthy controls and 11 patients with HCM, as well as late gadolinium enhancement (LGE) for detection of regional fibrosis.We performed cDTI Voxel-wise analysis of diffusion tensors relative to left ventricular coordinates showed expected transmural changes of myocardial helix-angle, with no significant differences between phases or between HCM and control groups. In controls, the angle of the second eigenvector of diffusion (E2A) relative to the local wall tangent plane was larger in systole than diastole, in accord with previously reported changes of laminar orientation. HCM hearts showed higher than normal global E2A in systole  and markedly raised E2A in diastole . In hypertrophic regions, E2A retained a high, systole-like angulation even in diastole, independent of LGE, while regions of normal wall thickness did not .In healthy controls, the angles of cross-myocyte components of diffusion were consistent with previously reported transmural orientations of laminar microstructures and their changes with contraction. In HCM, especially in hypertrophic regions, they were consistent with hypercontraction in systole and failure of relaxation in diastole. Further investigation of this finding is required as previously postulated effects of strain might be a confounding factor.The online version of this article (doi:10.1186/s12968-014-0087-8) contains supplementary material, which is available to authorized users. The compact myocardium of the left ventricle (LV) of humans and other mammals shows remarkable microstructural adaptation for global contractile function. Cardiomyocytes of the subendocardial and subepicardial layers contract almost orthogonally to each other, each angled obliquely, at helix-angles (HA) up to +60° and −60° relative to the circumferential alignments of myocytes of the mid layer ,2. This ex vivo studies of several regions of the LVs of different mammalian species . Thi species ,5,8,9.Ex vivo cardiac Diffusion Tensor Imaging (cDTI), based on measurements of diffusion distances of water molecules in myocardium, has been found capable of interrogating myocyte and sheetlet orientations [ntations ,8,10–12.ntations ,8. The antations ,7,8.The integrity and mobility of the laminar microstructures is thought to be fundamental for LV function and could be altered in cardiovascular disease. Hypertrophic Cardiomyopathy (HCM) is an autosomal dominant genetic disease, which can be caused by mutations in the genes responsible for encoding proteins of the cardiac sarcomere ,14. It iex vivo, and evidence for the phasic reorientations of laminar structures has been provided by static, explanted hearts imaged separately in contracted and relaxed states [in vivo at six different systolic trigger times [To date, most cDTI studies have been d states ,21. An eer times .in vivo pulse sequence for cDTI which draws on technical improvements and also the benefits of imaging at 3 T. Measures derived from this technique were recently shown to be reproducible in both controls and in HCM subjects [in vivo sequence to analyze the cross-myocyte components of diffusion, which we hypothesized would provide information on mean intravoxel sheetlet orientations and their changes between end-systole and late-diastole in controls and show abnormalities in patients with HCM.We have recently described the development of a novel subjects ,24. In tThis study was approved by the National Research Ethics Service. Eleven healthy controls and 11 patients with HCM were recruited and gave written informed consent. Data in systole from 6 patients was previously reported for reproducibility . ImagingIn order to ensure the same myocardial region was imaged with cDTI in systole and diastole, a breath-hold spoiled gradient echo (GRE) sequence with a spatial modulation of magnetization (SPAMM) tagging pre-pulse and a 45 ms temporal resolution was used to acquire four-chamber and two-chamber views. The linear tags were separated by 16 mm and were perpendicular to the long-axis with an acquired spatial resolution of 2.1 × 1.7 mm in-plane and slice thickness of 6 mm. The displacement of the linear tag closest to the central mid-ventricular slice was manually tracked from the systolic to the diastolic phase. The positioning of the cDTI central slice was manually adjusted between the systolic and the diastolic acquisition accordingly, with the inter-slice distance kept constant.in vivo cardiac diffusion weighted stimulated echo acquisition mode (STEAM) single shot echo planar imaging (EPI) sequence used has been previously described [2 (at a heart rate of 60 beats per minute), fat saturation, TR = 2 RR intervals = 2000 ms (at a heart rate of 60 beats per minute), TE = 23 ms, BW = 2442Hz/pixel, GRAPPA [2, interpolated to 1.35 × 1.35 mm2 (k-space zero-filling by a factor of two), field of view 360 × 123-157 mm2 and a minimum of 8 averages (one average per breathold). Three slices with 8 mm thickness were acquired in the mid ventricular short axis with an inter-slice gap of 4 mm. No partial Fourier was used. The sequence trigger time was set to acquire cDTI data during the systolic and diastolic rest periods. Localized first and second-order shimming and frequency adjustment were performed over the extent of the LV within the imaging planes. It should be noted that the sequence runs a spoiler gradient in place of the diffusion encoding gradients for the reference (b0) acquisitions, which introduces a small but not negligible diffusion weighting to the “b0” images. This is taken into account during the tensor calculation.The escribed . In shor, GRAPPA  parallelAdditional breath-hold CMR was performed to assess cardiac morphology and function in patients and controls. Retrospectively gated bSSFP cine sequences were acquired in 3 long-axis planes, followed by a contiguous stack of short-axis slices from the atrioventricular ring to the apex . Late gaVentricular volumes, function, mass, and ejection fraction was measured using a semi-automated threshold-based technique , with indexing to body surface area . The LV All quantitative tensor information was post-processed with custom software, written in-house using MATLAB . In a first step, all the raw diffusion-weighted images were analyzed visually to reject frames corrupted by breathing motion or abnormal RR intervals. A minimum of two averages per direction, after frame rejection, was set as a requirement for inclusion in the study. The accepted frames were then co-registered to correct for intra-subject variations in breath-hold position (in-plane only) with a cross-correlation based algorithm for rigid displacement . The subTwo diffusion tensor measurements were calculated from the eigensystem: Helix-angle (HA), and secondary eigenvector angle (E2A) ,29. HA aFor 3D visualization and comparison of E1 distributions, principal eigenvector tractography was performed, color coded according to helix-angle Figure A,B,E,F. To display mean intra voxel sheetlet angulation in the septal and anterior wall regions, the full diffusion tensor was represented by superquadric glyphs, and superimposed with long thin white cylinders, which represent the orientation of E2. The tensors were color coded according to their absolute E2A value : segments with hypertrophy and LGE (H+LG+); segments with hypertrophy but no LGE (H+LG-); and segments with no hypertrophy or LGE (H-LG-). Segments were included in the H+ or LG+ categories even if hypertrophy or late-enhancement were only partially included. Mean absolute E2A values were compared between groups with the Mann–Whitney–Wilcoxon test. Statistical significance was considered present when p < 0.05 after Bonferroni correction for the number of tests performed.The baseline demographics and clinical characteristics of control and patient groups showed no significant differences Table . The timAverage LV mass, wall thickness and ejection fraction were greater in the HCM group and end-systolic volume was smaller. The ventricular morphology, risk factors for sudden death and LGE patterns for the HCM patients are summarized in Table Figure cDTI was successfully performed on all subjects. Only 3.2% of all eigenvalues were spuriously negative, for which we assigned the positive mean values of adjoining voxels. In total the number of myocardial voxels analyzed for each group was: controls-systole 28,836 voxels; controls-diastole 26,034 voxels; HCM-systole 45,791 voxels; HCM-diastole 44,661 voxels. The greater number of voxels in HCM patients occurred because of LV hypertrophy. The measured E2 angles were found to be meaningful  and second (E2) directional components of intramyocardial diffusion in HCM patients as measured by cDTI. The LV helix-angle (HA) distribution . However E2A global mean values do not change substantially [The diffusion-encoding scheme used had only 6 directions. Recent DTI work in the brain showed comparable Mean Diffusivity (MD) and Fractional Anisotropy (FA) between 6 directions and 30 or 60 direction schemes (acquisition time kept constant) . DTI numantially .The averaging of non-positive definite tensors was performed for the eigenvalues directly. We appreciate that this is not a robust method, it maintains the neighbouring FA and MD, but it lacks sophisticated tensor interpolation. Nevertheless it affects only a small percentage (3.2%) of the eigenvalues measured, so we expect the impact to be small for the global means of E2A.In vivo cDTI in normals delivered apparently meaningful measurements of cross-myocyte diffusion, in keeping with previously reported myocardial sheetlet and shear layer reorientations from more wall-parallel in diastole to more wall-perpendicular in systole. In HCM, impaired diastolic reorientation of sheetlet populations was identified which was related to increased wall thickness and not LGE. The apparent persistence in diastole of a relatively systolic conformation in HCM may represent a novel in vivo human pathophysiological finding and would be consistent with biochemical studies and transgenic models that point to increased calcium sensitivity and impaired diastolic relaxation associated with known causative mutations.in vivo investigation of myocardial structural dynamics.Although the extent of the strain contribution to these results is currently uncertain, we believe that the measurements described in this study may represent a step towards in-vivo at the tissue level, combined with advances in the understanding of underlying molecular mechanisms, has potential for the development and evaluation of novel therapeutic approaches for patients with HCM.The potential of this novel non-invasive approach to assess HCM pathophysiology


Ranolazine is a new anti-anginal drug that acts via late sodium current inhibition, and has been shown to improve diastolic dysfunction in isolated myocytes. Diastolic dysfuntion is common in patients with aortic stenosis (AS), and precedes symptom development and systolic dysfunction. The purpose of this study was to assess the effects of ranolazine on peak early diastolic strain rate (PEDSR) and exercise capacity in patients with AS.Patients with asymptomatic moderate to severe AS and diastolic dysfunction underwent trans-thoracic echocardiography, exercise testing and cardiac magnetic resonance (CMR) imaging at baseline, 6 weeks after commencing ranolazine and at 10 weeks (4 weeks after discontinuation). Diastolic function was assessed using PEDSR measured on tagged CMR images.2) completed the week-6 visit and 13 completed the final visit. Global PEDSR did not significantly increase from baseline (0.79 ± 0.15) to week-6 . There was a borderline significant increase in total exercise duration from 10.47 ± 3.68 min to 11.60 ± 3.25 min (p = 0.06).Fifteen patients  contains supplementary material, which is available to authorized users. Aortic stenosis (AS) is the commonest valve lesion requiring surgery in the developed world , and itsThe mechanism of symptom generation in AS is unclear. The presence of left ventricular hypertrophy (LVH) and diastolic dysfunction appear to be important determinants of exercise capacity in AS –8. FolloCardiac magnetic resonance imaging (CMR) allows accurate quantification of LV mass, volumes and systolic function. Its also allows measurement of myocardial deformation in the form of strain and strain rates, and peak early diastolic strain rate (PEDSR), which measures the rate of myocardial relaxation, and is a largely load-independent measure of diastolic function . PEDSR h+) current, decreases intracellular calcium concentration and shortens the action potential duration, without clinically significant effects on heart rate or blood pressure. In experimental models, ranolazine has been shown to improve diastolic dysfunction in isolated myocytes [Ranolazine is a newly licensed drug for the treatment of chronic stable angina , 19. Ranmyocytes –22 and rmyocytes . In smalmyocytes  and imprmyocytes .The objectives of this pilot study were to assess the effects of Ranolazine on diastolic dysfunction, myocardial perfusion reserve (MPR) and exercise capacity in asymptomatic patients with moderate to severe AS with evidence of diastolic dysfunction and/or LVH.The study was a prospective, single centre, open label, single group, proof-of-concept study, with blinded endpoint analysis (EduraCT number 2011-000111-26). The United Kingdom National Research Ethics Service  approved the study and written informed consent was obtained from all subjects before participation. All imaging was analysed blinded to patient or visit information and the anonymised data was sent to the clinical trials unit (CTU), for unblinding and analysis at the end of the study.Patients were prospectively recruited from a single Cardiac centre. Inclusion criteria were: (1) moderate or severe AS , (2) asymptomatic, (3) evidence of diastolic dysfunction  or LVH , (4) age >18 years. Exclusion criteria were: (1) history of coronary artery bypass graft, myocardial infarction or angiographic coronary artery disease , (2) atrial fibrillation, (3) severe asthma (4) severe renal impairment (eGFR <30 ml/min), (5) hepatic impairment, (6) Concurrent administration of strong CYPA4 inhibitors or class I/III anti-arrhythmic agents, (7) QTc prolongation >470 ms, (8) Females of childbearing potential, (9) Use of >20 mg of simvastatin or >1000 mg of metformin during the study period.24H33N3O4, Gilead Sciences). This was up-titrated to 750 mg bd after 2 weeks, if tolerated, and continued for another 4 weeks. The study involved four outpatient visits to the hospital as outlined in Fig. Consented patients underwent venepuncture, electrocardiography (ECG), trans-thoracic echocardiography, exercise testing and stress CMR, before being commenced on 500 mg bd of ranolazine . or another pre-specified reason for stopping  >250 mmHg or diastolic blood pressure >120 mmHg or a fall in SBP >20 mmHg).CMR was performed on a 3-tesla (T) scanner  using an 18-channel phased array receiver coil Fig. . Steady CMR42 v4.2  was used to calculate the LV mass and volume data. Circumferential peak systolic strain (PSS), peak systolic strain rate (PSSR) and peak early diastolic strain rate (PEDSR) were calculated for each slice and globally  using the InTag post-processing plugin  for OsiriX  on the tagged images as previously described . The segThe primary hypothesis was that late sodium current inhibition with ranolazine would improve PEDSR, a measure of diastolic dysfunction, on tagged MRI. Secondary endpoints included MPR, exercise capacity and echocardiographic markers of diastolic function (E/E’).t tests were used to compare parameters between different visits. In addition, repeated measure analysis of variance (ANOVA) was used to compare parameters across the three visits. The results were further analysed after splitting the patients according to the median MPR, into low and high-MPR subgroups, and patient characteristics between the two sub-groups were compared using independent t test. Two-factor repeated measure ANOVA analysis was used to compare change in global PEDSR between the two sub-groups.In a previous group of eight AS patients tested 2 weeks apart, diastolic strain rate was 0.73 ± 0.22 and 0.71 ± 0.21 with paired mean difference of 0.04 and SD of 0.16. Sixteen patients with analysable images would allow us to detect a difference of 0.12 in diastolic strain rate with 80 % power, p < 0.05 and two-tailed. To allow for drop-outs and unanalysable image quality, we planned to recruit 20 patients. Statistical tests were performed using SPSS 20.0 software . Normality was assessed using the Shapiro–Wilk test, histograms and Q–Q plots. Continuous data are expressed as mean (standard deviation). Paired-samples Twenty patients consented to take part in the study but one patient was excluded after ECG showed atrial fibrillation. Nineteen completed the baseline visit, 4 withdrew before visit-3 and therefore, a total of 15 patients had data for the primary endpoint analysis at 6 weeks   at 3T, as used in this study, compared to CSPAMM tagging at 1.5T that was used to estimate the sample size . Additio+ current inhibition by ranolazine, leading to reduced extra-vascular compression of the coronary microcirculation, and improved myocardial blood flow. However, another study by the same group using vasodilator stress (n = 18), failed to show an improvement in myocardial perfusion [+ current. In a more recent pilot study of patients with microvascular angina, ranolazine did not lead to an improvement in coronary flow reserve, measured by Doppler echocardiography, in response to adenosine or cold pressor test [Our study did not demonstrate improvement in global MPR in the overall population following 6 weeks of ranolazine therapy. In a previous open-label pilot study of patients with coronary artery disease and perfusion defects on exercise SPECT myocardial perfusion imaging (n = 20), 4 weeks of treatment with ranolazine led to an improvement in myocardial perfusion pattern and severity . This iserfusion . Exercissor test .The total exercise time did show an increase at week-6, which was close to reaching statistical significance. This observation lends weight to the hypothesis that the small increase in PEDSR seen may be significant. We cannot discount that the increase in exercise capacity was related to improved technique on the treadmill, as there was no reduction in duration at week-10. However, the increase in exercise duration at week-6 was associated with a slightly reduced peak heart and blood pressure compared to baseline, and therefore a slightly lower exercise LVRPP , that were not sustained at week 10.Ranolazine may increase myocardial efficiency during exercise, and the mechanism for this may be related to an improvement in PEDSR. Ranolazine has previously been shown to increase exercise duration in multiple studies of patients with chronic stable angina , 19, 36.The major limitation of this study is its small sample size, with the results not reaching statistical significance. However the study was always planned as a pilot and the primary purpose was to assess the effect size. This hypothesis-generating study has certainly shown some interesting signals that merit further investigation in larger trials.In this pilot study, ranolazine did not show a significant improvement in diastolic dysfunction or MPR, in patients with moderate to severe AS. Given the low power of the current study, a larger study in patients with diastolic dysfunction is warranted and preferably conducted at 1.5T.The dataset supporting the results of this article is included in this article and its supporting file.


Left ventricular function is altered during and after AMI. Regional function can be determined by cardiac magnetic resonance (CMR) wall thickening, and velocity encoded (VE) strain analysis. The aims of this study were to investigate how regional myocardial wall function, assessed by CMR VE-strain and regional wall thickening, changes after acute myocardial infarction, and to determine if we could differentiate between ischemic, adjacent and remote segments of the left ventricle.99mTc tetrofosmin was administered intravenously and myocardial perfusion SPECT (MPS) was performed for determination of the ischemic area, followed by a second CMR study. Based on ischemia seen on MPS, the 17 AHA segments of the left ventricle was divided into 3 different categories . Regional wall function measured by wall thickening and VE-strain analysis was determined before and after ischemia.Ten pigs underwent baseline CMR study for assessment of wall thickening and VE-strain. Ischemia was then induced for 40-minutes by intracoronary balloon inflation in the left anterior descending coronary artery. During occlusion, Mean wall thickening decreased significantly in the ischemic  and adjacent segments (from 2.4 to 1.5 mm p < 0.001). In remote segments, wall thickening increased significantly . In ischemic and adjacent segments, both radial and longitudinal strain was significantly decreased after ischemia (p < 0.001). In remote segments there was a significant increase in radial strain (p = 0.002) while there was no difference in longitudinal strain (p = 0.69). ROC analysis was performed to determine thresholds distinguishing between the different regions. Sensitivity for determining ischemic segments ranged from 70-80%, and specificity from 72%-77%. There was a 9% increase in left ventricular mass after ischemia.Differentiation thresholds for wall thickening and VE-strain could be established to distinguish between ischemic, adjacent and remote segments but will, have limited applicability due to low sensitivity and specificity. There is a slight increase in radial strain in remote segments after ischemia. Edema was present mainly in the ischemic region but also in the combined adjacent and remote segments. Acute myocardial infarction (AMI) is a major cause of death worldwide despite diagnostic and therapeutic improvements . MortaliRegional left ventricular function is altered during and after AMI. This includes changes in the infarcted and ischemic regions as well as stunning in adjacent and remote areas of the myocardium –6. Most Cardiac magnetic resonance (CMR) is a comprehensive diagnostic tool that can provide accurate and reproducible measurements of cardiac volumes , dimensiMyocardial function in patients with AMI reaching the hospital has been well studied , 6, 18. Therefore, the aim of this study was to investigate how regional myocardial wall function, assessed by CMR velocity encoded strain and regional wall thickening, changes after acute myocardial infarction. In order to quantify absolute and relative regional changes we used an experimental pig model with induced ischemia and reperfusion using each animal as its own control. We also aimed to find out if we could differentiate between ischemic, adjacent and remote myocardium as determined by myocardial perfusion MPS by looking at regional myocardial function.The study conforms to the Guide for the Care and Use of Laboratory Animals, US National Institute of Health  and was approved by the Ethics Committee of Lund University, Sweden.99mTc tetrofosmin was administered intravenously prior to reperfusion and MPS was performed 2–3 hours after occlusion for determination of the area subjected to ischemia. A second CMR examination was performed approximately 3–4 hours after reperfusion. After the second CMR examination the animals were euthanized.Ten domestic pigs weighing 40–50 kg were fasted overnight with free access to water and all were premedicated with 2 mg/kg azaperone  administered intramuscularly 30 minutes before the procedure. Induction of anesthesia was performed with 5–25 mg/kg of thiopental . Administration of the anaesthetic was complemented with intermittent doses of meprobamat  and thiopental, if needed. Prior to inducing ischemia all pigs underwent a baseline CMR for assessment of wall thickening and velocity encoded strain. Ischemia was induced with inflation of an angioplasty balloon in the left anterior descending coronary artery distal to the first diagonal branch for 40 minutes. An angiogram was performed after inflation of the balloon and before deflation of the balloon in order to verify total occlusion of the coronary vessel and correct balloon positioning. After deflation of the balloon, a second angiogram was performed to verify restoration of blood flow in the previously occluded artery. During occlusion of the artery, Magnetic resonance imaging was performed on a Philips Intera CV 1.5 T  with a five element cardiac synergy coil before and after ischemia. All pigs were placed in supine position and scout images in the three orthogonal planes were acquired as guidance for determination of the standard imaging planes.For assessment of regional wall thickening steady state free precession (SSFP) cine images were acquired in the short-axis plane covering the entire left ventricle from base to apex. Images were also acquired in the 2, 3 and 4 chamber imaging planes. Image parameters were: repetition time 3.2 ms, echo time 1.6 ms, flip angle 60°, image resolution 1.36 × 1.36, slice thickness 8 mm, retrospective ECG gated reconstruction.From the short-axis cine images systolic wall thickness, wall thickening, and fractional wall thickening  were assessed before and after ischemia by manual tracing of the endocardial and epicardial borders. The left ventricle was divided in the American Heart Association 17 segment model. Papillary muscles were excluded from the myocardium. The most basal slice included in the analysis was the most basal short-axis slice containing myocardium in 360° of the left ventricular myocardial circumference in end-systole.All 2D in-plane velocity encoded data was acquired in the 2, 3 and 4 chamber imaging planes. Imaging parameters were: repetition time 23.4 ms echo time 4.6 ms, velocity encoding gradient 20 cm/s, flip angle 15°. Image resolution was typically 1.6 × 1.6 mm, and slice thickness 7 mm with 18–22 time frames per cardiac cycle, retrospective ECG gating.We used a previously validated method for VE strain analysis . In shorAn extracellular contrast agent  was administered intravenously at 0.2 mmol/kg 15 minutes before late gadolinium enhancement (LGE) images were acquired. Standard clinical imaging parameters were used for LGE imaging covering the left ventricle from base to apex by using an inversion-recovery gradient-echo sequence , with manually adjustment of the inversion time to null the signal from viable myocardium.The area of hyperenhancement was defined on the LGE short-axis images and was quantified using a previously described and validated semi-automatic algorithm  incorpor99mTc tetrofosmin  was administered intravenously ten minutes before deflation of the angioplasty balloon. The pigs were then imaged in a supine position using a dual head camera  at 32 projections (40s per projection) with a 64 x 64 matrix yielding a digital resolution of 5 x 5 x 5 mm. Short- and long-axis images, covering the left ventricle, gated to ECG, were then reconstructed.Five hundred MBq of For MPS analysis, automatic segmentation of the LV was performed . In shorhttp://segment.heiberg.se) [All image analyses were performed using an in-house developed freely available software  .In this study, the left ventricle was divided in the AHA 17-segment model for analysis . The 17 Wilcoxon Sign Rank test was used to assess changes in volumes, ejection fraction, cardiac output and heart rate. For changes in regional CMR wall thickening and VE strain we used a paired t-test. For all analysis, a p-value below 0.05 was considered significant. Values are expressed as mean ± SEM. To find thresholds to be able to discriminate between ischemic, adjacent and remote areas ROC analysis was performed. The ROC analysis was performed by evaluating sensitivity and specificity for different thresholds of wall thickening, radial strain, and longitudinal strain, respectively. The thresholds was tested in 1000 steps from minimum value to maximum value for each parameter.Table There was a significant increase in left ventricular mass from 86 ± 7 ml to 94 ± 15, an increase in 9% (p = 0.01) after ischemia. The increase in mass was not homogenous, and the increase in ischemic areas was 38% ± 3% (mean ± SEM) (p < 0.01), adjacent was 4% ± 2% (mean ± SEM) (p = ns), and in remote areas the increase was 7% ± 3% (mean ± SEM) (p = ns). When combining the results from remote and adjacent areas there was an increase in mass of 6% ±2% (p = ns).There was no statistically significant difference in wall thickening between the ischemic, adjacent and remote groups before induced ischemia.After reperfusion, the mean wall thickening decreased significantly in the ischemic  and adjacent segments (from 2.4 to 1.5 mm p < 0.001). In remote myocardium, however, wall thickening increased significantly . Figure Figure Before ischemia there was no statistically significant difference in radial or longitudinal strain in the later ischemic, adjacent and remote regions (p > 0.05).Figure There was a significant decrease in both radial and longitudinal strain between the ischemic and remote myocardium (both p < 0.0001) and between the ischemic and adjacent myocardium  between adjacent and remote myocardium .). The regional function expressed as radial strain in sectors defined as salvaged (i.e. containing any ischemic myocardium but no infarct) was 12 ± 10%. There was no significant difference between regional strain in salvaged sectors versus adjacent sectors (p = 0.79).Figure Figure In this study we found that there is a significant decrease in regional wall function in the ischemic and adjacent segments of the left ventricle measured by CMR wall thickening and VE-strain after induced myocardial infarction. There is a slight increase in regional wall function seen by wall thickening and VE radial strain in remote myocardium. The non-significant increase in longitudinal strain seen in the remote myocardium was likely attributed to the limited number of subjects.The decreased function in the ischemic region is well known and has obvious causes.The reduced regional function in adjacent areas have been described previously  and reprIn this study we found that there was a slight, but statistically significant, increase in regional myocardial function in remote areas measured both by wall thickness and radial strain. There was, however, no change in function seen by longitudinal strain. Increased function in remote areas has been described previously , 7, 28 bIn a direct comparison between strain tagging and wall thickening, a previous study by Götte et al.  using CMWe also found an increase of left ventricular mass of 9% following ischemia that is likely caused by edema. The increase was impressive in the ischemic area, measuring 37% ± 3% (p < 0.01) compared to 6% ± 2 (p = ns) in the combined remote and adjacent areas. This was also supported by end diastolic thickness that was significantly higher in ischemic compared to remote sectors (p < 0.01).The study was conducted on 10 pigs, all with occlusion of the LAD. How results for CMR wall thickening and VE-strain would be affected by right coronary artery or left circumflex occlusion remains to be studied. In wall thickening, the most basal slices in end-diastole are often excluded since myocardium cannot be found in 360° of the left ventricular myocardial circumference in end-systole due to long-axis AV-plane motion . No stanThresholds for wall thickening and strain could be established for differentiation between ischemic, adjacent and remote areas. These thresholds, however will have limited clinical applicability due to the low sensitivity and specificity. Regional left ventricular function is reduced in the ischemic and areas adjacent to the ischemia after reperfused anterior myocardial infarction, while there is a slight increase in radial function in remote areas of the left ventricle. Edema was present mainly in the ischemic region but also to a slighter degree in the combined adjacent and remote areas.


Patients with repaired tetralogy of Fallot (rTOF) suffer from progressive ventricular dysfunction decades after their surgical repair. We hypothesized that measures of ventricular strain and dyssynchrony would predict deterioration of ventricular function in patients with rTOF.A database search identified all patients at a single institution with rTOF who underwent cardiovascular magnetic resonance (CMR) at least twice, >6 months apart, without intervening surgical or catheter procedures. Seven primary predictors were derived from the first CMR using a custom feature tracking algorithm: left (LV), right (RV) and inter-ventricular dyssynchrony, LV and RV peak global circumferential strains, and LV and RV peak global longitudinal strains. Three outcomes were defined, whose changes were assessed over time: RV end-diastolic volume, and RV and LV ejection fraction. Multivariate linear mixed models were fit to investigate relationships of outcomes to predictors and ten potential baseline confounders.One hundred fifty-three patients with rTOF  were included. The mean follow-up duration between the first and last CMR was 2.9 ± 1.3 years. After adjustment for confounders, none of the 7 primary predictors were significantly associated with change over time in the 3 outcome variables. Only 1–17 % of the variability in the change over time in the outcome variables was explained by the baseline predictors and potential confounders.In patients with repaired tetralogy of Fallot, ventricular dyssynchrony and global strain derived from cine CMR were not significantly related to changes in ventricular size and function over time. The ability to predict deterioration in ventricular function in patients with rTOF using current methods is limited.The online version of this article (doi:10.1186/s12968-016-0268-8) contains supplementary material, which is available to authorized users. Surgical repair of tetralogy of Fallot (TOF) in early childhood has achieved great success with a low mortality of less than 3 % . HoweverNot all patients with repaired TOF (rTOF) develop progressive dysfunction in the setting of chronic PR. Unfortunately, no clinical measures have been reported to predict deterioration in function and dilation. For example, a recent study by Wald et al.  investigMeasures of cardiac mechanics, such as ventricular dyssynchrony and strain, are strong predictors of adverse outcomes in patients with cardiovascular disease , 10. PatPatients fulfilling the following criteria were retrospectively identified from a database search at Boston Children’s Hospital: 1) diagnosis of rTOF; 2) at least 2 CMR examinations with assessment of ventricular size and function greater than 6 months apart, acquired between May 2005 and March 2012; 3) no intervening surgery or catheter procedures between the CMR examinations; 4) a 12-lead ECG at the time of first CMR. If a patient had at least 2 CMR scans before an intervening procedure, their data were included in the study up to the point of the procedure. Patients with incomplete or poor quality CMR were excluded.2, flip angle 60°, TR 2.7–3.6 ms, TE 1.4–1.8 ms, slice thickness 6–8 mm, slice gap 0–2 mm. Horizontal and vertical long-axis images were used for identification of valve planes. Cine phase-contrast images perpendicular to the main PA were used for quantification of the PR fraction.CMR was performed on a 1.5 T Philips Achieva scanner with a 32-element phased array cardiac coil . ECG-gated steady-state free precession (SSFP) short-axis images spanning the ventricles were acquired during 10–15 s breath holds with 20–30 image frames per cardiac cycle. Acquisition parameters were: matrix 256 x 256, field of view 240–460 mmLV and RV end-diastolic (EDV) and end-systolic volumes (ESV), and ejection fractions (EFs) were quantified from all CMR scans using Qmass  as previously described . VentricCMR images from the baseline study were used to quantify cardiac dyssynchrony and strain using custom feature tracking software written in MATLAB . A detailed description of the method was reported in a previous study . BrieflyTo quantify dyssynchrony, cross-correlation delays for each of the segmental strain curves  were calculated relative to a patient-specific reference curve derived from the LV of each patient . Intra-vPeak circumferential strain of each ventricle was calculated as the most negative peak of the global strain curve obtained by averaging all segmental strain curves across all selected short-axis slices. Similarly, peak longitudinal strain of each ventricle was calculated from a four-chamber slice. Absolute values of the peak strains were reported.Three primary outcomes were defined to measure deterioration in ventricular size and function over time: RVEDV indexed to body surface area, RVEF and LVEF. Changes in the outcomes are represented as ΔRVEDVi, ΔRVEF and ΔLVEF, respectively. Seven potential primary predictors were defined at baseline: LV, RV and inter-ventricular dyssynchrony, LV and RV peak circumferential strains, and LV and RV peak longitudinal strains. Ten potential confounders measured at baseline were also included in the analysis: RVEDVi, RVEF, LVEF, indexed RVESV (RVESVi), PR fraction, QRS duration, heart rate, age at first CMR, age at initial repair, and type of initial repair , with two-group comparisons based on T tests or Fisher’s exact test. Post-hoc linear regressions were also fit to assess change over time in relation to time elapsed for selected outcomes, overall and within strata defined by quartiles of baseline predictors.Statistical analyses were performed in SAS Version 9.3  and MATLAB. The three outcomes  were treated as continuous variables and analyzed with linear mixed models to assess how their baseline levels and changes over time were associated with various potential predictors and confounders. A primary multivariate analysis with the same outcomes was also performed, in which multiple potential predictors and confounders and their interactions with time were included simultaneously after selection by a backward elimination process. Normalized mixed model coefficient estimates  are reported. The normalized coefficients are roughly comparable to the linear correlation coefficient r. An auxiliary multivariate analysis was performed to estimate the proportions of variability in the outcomes’ changes over time which were accounted for by covariates in the primary multivariate analysis; the auxiliary multivariate analysis replaced the outcomes by difference quotient approximations to their time derivatives and included only those covariates interacting with time in the primary multivariate analysis. Statistical significance was defined by 2, 2) decrease in RVEF ≥10 absolute percentage points, or 3) decrease in LVEF ≥10 absolute percentage points. Conversely, patients fulfilling all three of the following criteria were classified as no deterioration: 1) increase in RVEDVi ≤5 mL/m2, 2) decrease in RVEF ≤3 absolute percentage points, and 3) decrease in LVEF ≤3 absolute percentage points. Threshold values were selected based on a previous study [A subgroup analysis was conducted between patients with pronounced deterioration in ventricular function and/or worsening ventricular dilation and patients who had no deterioration. Pronounced deterioration was defined as the fulfillment of any of the following criteria: 1) increase in RVEDVi ≥30 mL/mus study . UnpaireBecause the assessment of global function, including peak global strains, may mask potentially important regional dysfunction, the entire analysis was repeated by replacing the above peak global strains with peak regional strains. For each ventricle, peak circumferential strain was assessed in nine regions while longitudinal strain was assessed in two regions from the four-chamber image.n = 97). All patients were in normal sinus rhythm, and the mean QRS duration (136 ± 27 ms) was prolonged. Ninety-two percent (n = 140) of the patients had right bundle branch block on ECG.The database search identified 164 patients based on the inclusion criteria, among which 4 had incomplete imaging data, and 7 were excluded due to poor image quality. A total of 153 patients with rTOF  were included for analysis. Demographic, surgical and ECG data are summarized in Table CMR parameters evaluated at the baseline scan are listed in Table Results of the seven primary predictors are included in Table 2), and small decreases in LVEF (2 ± 6 %) and RVEF (3 ± 6 %). The mean rate of change per year was 2 ± 10 mL/m2 for RVEDVi, -1 ± 3 % for LVEF and -1 ± 3 % for RVEF .Change in ventricular size and ejection fraction computed between the first and last CMR scans are summarized in Table p < 0.001) and ∆RVEF ; however, the direction of correlation was negative  and weakly correlated with ∆RVEF . Similarly, baseline RVEF was weakly correlated with ∆RVEF . A similar negative correlation was also seen between baseline QRS duration and ∆RVEF . However, as quantified by the auxiliary multivariate analysis, covariates in the primary multivariate analysis explained only 1 %, 17 % and 9 % of the variability in ∆RVEDVi, ∆RVEF and ∆LVEF, respectively.A summary of the results from multivariate analysis is shown in Table p = 0.02, Fig. p = 0.06, Fig. Out of 153 patients in the study, 37 (24 %) patients had pronounced deterioration and 38 (25 %) patients had no deterioration. Seventy-eight patients did not fulfill criteria for either group (i.e. their deterioration was not pronounced). Between the 2 groups, there were no differences in measures of dyssynchrony or longitudinal strains Table . Patientp < 0.001), RVEF  and RVEDVi  compared to the group without deterioration. QRS duration, heart rate, age at initial repair, PR fraction and RVESVi were no different between the two groups (Table p = 0.03): the deterioration group had more patients with a transannular patch repair and the no deterioration group had more patients with a non-transannular patch repair.In addition, patients with pronounced deterioration also had higher baseline LVEF  measures of ventricular dyssynchrony are not correlated with changes in ventricular volume and ejection fraction over time; 2) baseline LV and RV peak global circumferential/longitudinal strains correlate weakly and negatively with ∆LVEF and ∆RVEF before adjusting for baseline confounders, but they are not significantly associated with ∆LVEF or ∆RVEF after adjustment for potential confounders; 3) multivariate analysis shows baseline LV and RV EF are correlated to ∆LVEF and ∆RVEF after adjusting for confounders, yet the direction of correlation is negative.Progressive RV dilation as well as LV and RV dysfunction are commonly seen in patients with rTOF, and have been identified as independent predictors of adverse clinical status in this patient population –7. DeterBased on findings that cardiac strain and dyssynchrony are strong predictors of adverse outcomes in other diseases , 10, we Consistent with previous work, we observed intra- and inter-ventricular dyssynchrony –15, 26 aFinally, after adjusting for baseline confounders, none of the seven primary predictors were significantly associated with ∆RVEDVi, ∆RVEF or ∆LVEF. The ultimate exclusion of global peak strains  from the multivariate model was likely due to their tight correlation with LV and RV EF at baseline (data not shown).Multivariate analysis showed that baseline LV and RV EFs were significantly correlated with ∆EFs. These correlations were also negative, consistent with the finding from the subgroup analysis. Similarly, Wald et al.  reportedIn the current study, we did not identify any variables that were independently associated with changes in RVEDVi over time. This could be due to the generally small changes in RVEDVi in this cohort during the study period. In the subgroup analysis, patients with pronounced deterioration had higher RVEDVi at baseline compared to the non-deterioration group. Similarly, Luijnenburg et al.  has repoThe type of the initial repair has been suggested as a predictor for clinical status . PatientIt is worth noting that with all potential predictors and confounders considered, only a few confounders remained in the final multivariate model, and the parameters remaining in the model could explain no more than 17 % of the variations in changes over time in the three outcomes. Even when global strains were replaced with regional strains in the analyses, only one regional strain remained significant and it was weakly correlated to a change in an outcome variable. This finding is likely spurious, as the predictive ability of the model increased by only 1 % upon including this regional strain. This suggests that our ability to predict deterioration of ventricular function in patients with rTOF is limited. There are likely unknown factors that play critical roles in mediating deterioration of the disease, and this demands further investigation.Patients with interventions were excluded from the current study, which may have limited our study subjects to asymptomatic patients or patients with mild deterioration in ventricular dysfunction. However, those who had at least two CMR scans before any intervention were still included. Also, patients who had contraindications for CMR  were not able to be included in the study.Peak strains in the current study were quantified using feature tracking from SSFP images. While feature tracking has shown moderate reproducibility for quantifying RV strains  and alloFeature-tracking based measures of cardiac mechanics  do not independently predict changes in ventricular size and ejection fraction over time in patients with repaired tetralogy of Fallot. The ability to predict deterioration in cardiac function using currently available methods is very poor; less than 17 % of the variations in the outcomes could be explained by the multivariate model. These findings suggest that patients with repaired tetralogy of Fallot require similar clinical follow-up, including CMR evaluations to assess ventricular size and ejection fraction, regardless of their clinical status.(r)TOF, (repaired) tetralogy of Fallot; CMR, cardiovascular magnetic resonance; DENSE, displacement encoding with stimulated echoes; ECG, electrocardiogram; EDV(i), (indexed) end-diastolic volume; EF, ejection fraction; ESV(i), (indexed) end-systolic volume; LV, left ventricle/ventricular; PR, pulmonary regurgitation; RV, right ventricle/ventricular; SD, standard deviation; SSFP, steady-state free precession


Diastolic function (DF) is not routinely assessed by cardiac MR (CMR), but is critical for assessment of common disease states such as heart failure or hypertrophy. At present, special pulse sequences  are necessary for CMR for diastolic function assessment. The purpose of this study was to assess cine CMR volumetric assessment of DF using a 3D model-based analysis, in reference to 2D phase contrast and echocardiography (echo).In this IRB-approved retrospective study, consecutive subjects with HCM who underwent both echo and cardiac MRI from December 2011 to June 2013 were identified from the radiology database. Cine steady state free precession (SSFP) images  were analyzed using a semiautomated 3D model-based analysis of left ventricular filling curve . Transmitral flow curves were measured from 2D phase contrast (PC) using dedicated software . DF on echo was obtained from the medical records. Correlation of E/A ratio and E/E' ratio among CIM, 2D PC, and echo was calculated using Pearson's correlation coefficient. Differences in CIM E/A and E/E' ratios among DF groups were analyzed using ANOVA.64 subjects were included; 49 males (76.6%) and 15 females (23.4%), with mean age of 53.3 years. CIM E/A and E/E' ratios were analyzable in 62 patients and 38 patients, respectively. DF grades on echo were: grade 0 (n = 16), grade 1 (n = 9), grade 2 (n = 29), grade 3 (n = 6), and not available (n = 4). Due to abnormal cardiac morphology of HCM patients, CIM software had minor difficulties with semiautomated contour tracking, which was easily adjustable by the user. CIM performed well in tracking of valve motion. There was strong correlation between E/A ratio of CIM and 2D PC  and between E/A ratio of CIM and echo . There was no significant correlation between E/E' ratio of CIM and 2D PC  and between E/E' ratio of CIM and echo , likely due to smaller sample size. There was significant difference in CIM E/A ratio among DF groups on one-way ANOVA (p < 0.001). Difference in CIM E/E' ratio among DF groups approached significance (p = 0.106).Semiautomated 3D model-based analysis of left ventricular filling curve is a promising technique for evaluation of DF in patients with hypertrophic cardiomyopathy, demonstrating good correlation with 2D phase contrast and echo in assessment of E/A ratio. DF can be measured accurately using routine cine SSFP images and semiautomated analysis of left ventricular filling curve, without the need for specialized pulse sequences.Linda Chu received research support from RSNA R&E Foundation Fellow Grant.


Unlike other parts of the world in which cardiomyopathy is rare, heart muscle disease is endemic in Africa. The major forms of cardiomyopathy in Africa are dilated cardiomyopathy (DCM) and endomyocardial fibrosis (EMF). Whereas DCM is a major cause of heart failure throughout the continent, EMF is restricted to the tropical regions of East, Central, and West Africa. Although epidemiological studies are lacking, hypertrophic cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy seem to have characteristics similar to those of other populations elsewhere in the world.Recent advances in the genetic analysis of DCM in other parts of the world indicate that it is a genetically heterogeneous disorder in which some cases have a Mendelian cause and others have a non-genetic or multifactorial cause. This heterogeneous pattern of inheritance has been confirmed in small studies that have been conducted so far in Africa. The advent of human immunodeficiency virus infection and its association with cardiomyopathy has emphasised the role of inflammatory agents in the pathogenesis of DCM.By contrast with DCM in which some cases have major genetic contributions, there is scanty evidence for the role of genetic factors in the aetiology of EMF. Although the pathogenesis of EMF is not fully understood, it appears that the conditioning factor may be geography , the triggering factor may be an as yet unidentified infective agent, and the perpetuating factor may be eosinophilia. There is a need for renewed effort to identify genetic and non-genetic factors in EMF and other forms of heart muscle disease that are prevalent on the continent of Africa. The sequencing of the human genome has raised afresh the age-old debate on the relative importance of nature  and nurture  in the aetiology of human disease. There are, however, at least three lines of epidemiological evidence that emphasise the dominant role of environmental factors in the causation of the common forms of heart disease.First, it is well established that the type and the burden of heart disease change over time as a country undergoes economic development. Developing countries begin with a disease profile that is dominated by nutritional, perinatal and infectious diseases and, in the process of development, make the transition to one dominated by non-communicable diseases, such as cardiovascular disease and cancer.Indeed, the modest effect of inherited factors has been quantified at an epidemiological level in INTERHEART, the case-control study of risk factors for myocardial infarction conducted in all major continental populations, which has shown that family history (a combined measure of inherited factors) probably accounts for 1% of the overall population-attributable risk of the myocardial infarction.5Cardiomyopathy of undetermined cause has been known to be endemic in Africa for over 60 years.7The major forms of cardiomyopathy in Africa are dilated cardiomyopathy (DCM) and endomyocardial fibrosis (EMF).DCM is a primary disorder of heart muscle that is characterised by dilatation and impaired contraction of the chambers of the heart. Presentation is usually with heart failure, which is progressive, with a four-year mortality of 34% after the onset of symptoms.8The cases of DCM that remain unexplained even after intensive investigation are a major challenge to the clinician and the researcher. The aetiological factors that have been examined in Africans include ‘burnt-out’, untreated hypertension, infection and myocarditis, auto-immune mechanisms, iron overload, excessive alcohol intake, nutritional deficiency, and pregnancy. Sliwa and her colleagues recently conducted a general overview of studies of these potential aetiological factors.6A major advance in the study of the pathogenesis of unexplained DCM in other parts of the world has been the demonstration that 20 to 50% of cases are familial, suggesting that genetic factors may be involved in the aetiology of the condition.9 Reported families most commonly are compatible with autosomal-dominant inheritance, but some with X-linked and autosomal-recessive inheritance have been documented. Familial DCM is caused by mutations in at least 25 chromosome loci where genes encoding contractile, cytoskeletal and calcium regulatory proteins have been identified, underlining the genetic heterogeneity of the condition.10et al. have shown that familial progressive heart block type II, which was initially reported in 1977, may be associated with DCM in the late stages of the disease.15To the best of our knowledge, the first report of familial DCM in Africa described twin brothers in Uganda.Apart from these reports, we are not aware of systematic family studies that have been conducted to establish the frequency of familial DCM in Africans, such as has been done elsewhere.An association with HLA-DR1 and DRw10 antigens has been reported in South African patients, implying that genetically determined immune-response factors play a role in the pathogenesis of some individuals with DCM.20The advent of the human immunodeficiency virus (HIV) epidemic in Africa presents new opportunities for the study of the interaction between an environmental factor, such as HIV, and heart muscle disease.21Cross-sectional and retrospective studies suggest that cardiomyopathy is the leading cause of heart disease, among other systemic and protean manifestations of immunosuppression, in acutely ill hospitalised patients with HIV in Africa. While some patients with left ventricular dysfunction present with features of cardiac failure, the majority has left ventricular dysfunction detected only by echocardiography, without any clinical suggestion of heart failure. HIV-associated cardiomyopathy is characterised by global systolic functional impairment with or without left ventricular dilatation.et al. found no evidence of systolic dysfunction but a high frequency of diastolic dysfunction (86%) and left ventricular hypertrophy (47%).In studies of asymptomatic patients with HIV infection, left ventricular systolic dysfunction is found less frequently. In a study of 49 asymptomatic patients, Longo-Mbenza Endomyocardial fibrosis is a form of restrictive cardiomyopathy in which dense fibrosis in the mural endocardium restricts ventricular diastole and entraps the papillary muscles of the atrioventricular valves. EMF occurs mainly in tropical and subtropical areas worldwide. In Africa, the first awareness of EMF is ascribable to Williams in Uganda.EMF is said to be the most common form of heart disease in Ugandan hospitals where it accounts for nearly 20% of cases referred to an echocardiography service.The clinical features of EMF depend on the stage of disease and the anatomical involvement of the heart. Thirty to 50% of children and adolescents report an initial illness with fever, chills, night sweats, facial swelling and urticaria.32Several environmental  and inherited (ethnicity) factors have been implicated in the pathogenesis of EMF in Africa. There is, however, no compelling evidence supporting the contribution of inherited factors in the pathogenesis of EMF. While in Uganda the disease is said to be more common among immigrants from neighbouring Rwanda and Burundi who have settled in specific geographic districts of the country,6Eosinophilia has also been proposed as a major risk factor for EMF in both Uganda and Nigeria.39The pathogenesis of EMF remains elusive. It appears, however, that the conditioning factor is geography , the triggering factor may be an as yet unidentified infective agent, and the perpetuating factor may be eosinophilia. The demonstrated role of auto-immunity requires further study.41Hypertrophic cardiomyopathy (HCM) is recognised in Africans and other populations as an autosomal-dominant disorder that is caused by mutations in at least 11 different genes that code for sarcomeric proteins.9Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterised macroscopically by dilatation and reduced systolic function of the right ventricle, and microscopically by myocardial cell loss with partial or total replacement of the right ventricular muscle by adipose and fibrous tissue. ARVC was reported for the first time in Africa in 2000,6The contribution of inherited factors to the pathogenesis of the cardiomyopathies vary from hypertrophic cardiomyopathy  to EMF


MitraClipTM-implantation has been shown to significantly reduce mitral regurgitation (MR) in patients with high surgical risk. Whereas hemodynamic and echocardiographic studies suggest a reduction in left ventricular (LV) volumes and an increase in cardiac output following the intervention, there is very limited data on assessment of volumetric and functional changes after MitraClipTM-implantation using cardiac magnetic resonance (CMR) imaging, the considered method of choice in such a scenario.Patients with moderate to severe MR, high surgical risk and absence of contraindications to CMR imaging underwent MitraClipTM-implantation and CMR imaging on a 1.5 Tesla scanner  before and within seven days after the procedure. In addition to volumetric and flow studies, myocardial feature tracking (FT) technology for quantification of myocardial wall mechanics was applied. From steady-state free precession images of short axis views LV maximal circumferential (ECCSAX) and radial (ERRSAX) and of the 4-chamber view LV longitudinal (ELL4CH) and radial (ERR4CH) strain was calculated using dedicated prototype software .Twenty patients (age: 76 ± 8 years) with functional MR (n = 15) or degenerative MR (n = 5) with a median Euroscore of 33 (range 17-62) underwent the MitraClip-procedure and CMR imaging. Detailed results of volumetric assessment of the LV and right ventricle (RV) as well as calculated mitral and tricuspid regurgitation fraction are summarized within the table. There was a 44% relative reduction in MR fraction after MitraClipTM-implantation. In this severely compromised patient population (mean pre-implant cardiac index of 1.7 L/min/m2), there were smaller LV enddiastolic volumes after the intervention, but reduced total stroke volume at unchanged effective LV stroke volume (=net aortic forward flow) and cardiac index. RV volumes, RV function and tricuspid regurgitation were unchanged following the intervention. Whereas global LV systolic function (ejection fraction) remained unchanged, there was significant impairment of the following measures of LV strain: ECCSAX  and ERRSAX  at mitral valve level and ERR4CH . Other measures of LV strain were not altered significantly.In severely compromised patients, marked reduction in mitral regurgitation by MitraClipTM-implantation might not result in improved cardiac output and effective biventricular forward flow. Further analyses need to clarify whether impaired LV strain in particular at the level of the mitral valve is related to altered loading conditions or is a consequence of worsened interaction between the mitral valve and the basal myocardial segments of the LV due to the MitraClipTM placement itself.None.