Pulsed wave Doppler derived cardiac output correlated well with cardiac output estimated using the thermodilution method . The LV global longitudinal strain was -21.3 ± 3.9 % and the RV global longitudinal strain was -15.4 ± 2.5 %. LV GWI was 1885(1281–2121) mmHg*% and 297 ± 62 mmHg*% for the RV. LV global myocardial work efficiency was 82.6 ± 4 % and 83(72–88) % for the RV. TEE offers sufficient morphological, functional and hemodynamic assessment of the heart in swine. Myocardial contractility and mechanics can be reliably evaluated with the non-invasive GWI derived from echocardiography without additional invasive measures.This study aimed to determine standard left (LV) and right ventricular (RV) transesophageal echocardiographic (TEE) measurements in swine. Additionally, global myocardial work index (GWI) was estimated using pressure-strain loops (PSL). A comprehensive TEE examination was conducted in ten anesthetized, intubated and mechanically ventilated healthy female German landrace swine, weighing 44 to 57 kg. For GWI calculation, we performed LV and RV segmental strain analysis and used invasively measured LV and RV pressure to obtain PSL. The GWI and further myocardial work indices were calculated from the area of the PSL using commercially available software. Furthermore, hemodynamic measurements were obtained using indwelling catheters. We obtained complete standardized baseline values for left and right ventricular dimensions and function. Biplane LV ejection fraction was 63 ± 7 % and the LV end-diastolic volume was 70.5 ± 5.9 ml. Tissue Doppler estimated peak tricuspid annular systolic velocity was 13.1 ± 1.8 cm/s. The Doppler estimated LV and RV stroke volume index were 75.6 ± 7.2 ml/m Echocardiography is an invaluable diagnostic tool for analysis of cardiac anatomy and function , 2. TherThe experimental protocol was approved by the appropriate governmental institution . All animals received adequate care according to the precepts of the Helsinki Declaration of 1964 and its later amendments. Ten healthy female swine  weighing 44 to 57 kg were used in this prospective study. The pigs were approximately four months of age. Veterinary inspection on arrival helped to ensure a consistently thorough health status. Animals were housed in pens with a 12 h-day-night cycle and access to drinking water ad libitum. Twelve hours prior to the experiment, animals were set on nil per os, except for drinking water access.Weighing of the animals was performed before experiments were started. General anesthesia was induced by intramuscular injection of 4 mg/kg azaperone , followed by intravenous injection of 15 mg/kg sodium pentobarbital . Anesthesia was preserved by continuous intravenous sodium pentobarbital infusion at a rate of 4 mg/kg/h. Placed in supine position, animals were orotracheally intubated and legs were carefully fixed in an extended position. Animals were ventilated with an inspiratory oxygen fraction of 0.3 . Tidal volume was set to 10 ml/kg and respiratory rate was adjusted to keep the end-tidal carbon dioxide tension within a physiologic range (35 ± 4 mmHg). Continuous five lead electrocardiogram (ECG) and pulse oximetry were performed. Convective heating was used to maintain swine’s body temperature at 38.0 ± 0.5°C during preparation . At completion of the protocol, anesthesia was stopped and animals were weaned from the ventilator.TD) measurements by thermodilution, a Swan-Ganz catheter  was flow-directed into the pulmonary artery and connected to a cardiac output monitor . When hemodynamic monitoring had been fully established, animals were left untreated for approximately thirty minutes. After this stabilization period, comprehensive baseline measurements were obtained.Arterial blood pressure was obtained using a fluid-filled catheter , that was placed into the left femoral artery. For pulmonary artery pressure and cardiac output (COEchocardiography was performed using a GE Vivid E9 system equipped with a 6VT-D (3.0–8.0MHz) TEE probe . Frames were recorded ECG-synchronized from at least three consecutive cardiac cycles and stored on a hard disk. Two experienced and certificated sonographers performed the TEEs and the offline data analysis. TEE studies and chamber quantification were performed according to the guidelines of the American Society of echocardiography and the European association of cardiovascular imaging , 21. TheFor placement of the TEE-probe, a custom-made bite guard was inserted into the pig’s snout. The probe was protected by an ultrasound gel filled probe cover. Before probe introduction, we lubricated the coat’s outer surface with ultrasound gel. To avoid advancement into the porcine pharyngeal pouch, the tongue was lifted with a spatula, and the TEE probe was carefully inserted from the right side of the pig’s pharynx, applying minimum force , 22.In general, anteflexion and lateroflexion of the probe was needed for unaffected imaging. Small adjustments in rotation, depth and flection of the probe were made in every animal to adapt to the individual anatomy. At 0–20° array position with slight retroflexion, the echocardiographic evaluation was started with a mid-esophageal modified four-chamber (4CH) view Fig. a. In addLV dimensions were measured in the mid-esophageal 4CH view and deep esophageal 2CH view in systole and diastole. Left ventricular end-diastolic and end-systolic volumes  were determined using biplane method of disk summation, also known as Simpson’s biplane method as recommended by ASE and EACVI .1, mid diameter D2 and longitudinal diameter D3 were measured in the mid-esophageal modified 4CH view.RV basal diameter DEjection fraction (EF) was calculated using the modified biplane Simpson’s method.vol) was calculated using the volumetric Simpson’s method. For calculation of the stroke volume index, body surface area (BSA) was calculated from the body weight using the following equation [Cardiac output  and the tricuspid annular systolic velocity (TASV) were determined as indices of right ventricular function in the 4CH view. Endocardial right ventricular borders were traced in end-systole and end-diastole to obtain the corresponding RV areas. Subsequently, RVFAC was calculated :\documenentclass1pt{minimaPWD) was computed using the following equations [Pulsed wave Doppler (PWD) was applied in the LAX-views of the pulmonary and the aortic valve to obtain the corresponding velocity time integrals (VTI) from the left (LVOT) and right (RVOT) ventricular outflow tract Fig. b and c. quations .\documenMyocardial deformation imaging using 2DSTE offers an advanced LV quantification beyond ejection fraction (EF) . HoweverBefore performing 2DSTE, aortic and mitral valve opening and closure time were determined by pulsed-Doppler from the mid-esophageal LAX view. Deformation imaging of the LV was applied in the mid-esophageal modified 4CH-, LAX- and deep-esophageal 2CH views Fig. a. To perGWI: the total area of the PSL represents the total work from mitral valve closure to mitral valve opening.Constructive MW (GCW): work of the LV, which contributes to the LV ejection during systole. Constructive MW is defined as shortening of the myocytes during systole. GCW = positive Work during systole + negative work during isovolumic relaxation.Wasted MW (GWW): Work of the LV that does not contribute to the LV-ejection. Wasted MW is defined as lengthening of the myocytes (instead of shortening) during systole, which further intensifies the shortening during the isovolumic relaxation phase. GWW = negative work during systole + positive work during isovolumic relaxation.MW Efficiency (GWE): is the fraction of constructive MW to total work and calculated by GCW/(GCW + GWW) , 18.EchoPAC software creates an adjusted LV pressure curve corresponding to the duration of isovolumic and ejection phases determined by valvular timing events. As described by Russel et al. , 18, thep value smaller than 0.05 was considered significant.We used SPSS statistics Version 26  for data analysis. Normal distribution was confirmed using Kolmogorov–Smirnov test. Normal distributed measurements are expressed as mean ± standard deviation. If normal distribution was not present, data are expressed as median followed by range in brackets. To test for correlation between CO derived from indwelling catheters and echocardiographic measurements, we ran a Pearson correlation test. A We carried out a comprehensive TEE examination in 10 healthy female swine with a median body weight of 46.1 (43.6–56.7) kg. Study acquisition took on average between 20 and 30 min per animal. No adverse events concerning TEE probe insertion or TEE-study acquisition in general were observed. All the above-described views and structures could be visualized in each animal. No preexisting cardiac conditions were found in any of the examined animals.1 was 3.3 ± 0.4 cm, mid diameter D2 was 2.5 (2.4–3.1) cm and longitudinal diameter D3 was 4.4 ± 0.2 cm.LVEDV was 70.7 ± 4.4 ml and LVESV was 32.6 ± 3.8 ml. RV basal diameter D2 for LV and 76.7 ± 7.8 ml/m2 for RV.RVFAC was 44 ± 6 % and TASV was 13.1 ± 1.8 cm/s. General physiological parameters as well as TEE data about ventricular size and function are presented in Table GLS was -21.3 ± 3.9% for LV and − 15.4 ± 2.5% for RV. GWI was 1885 (1281-2121) mmHg*% for LV and 297 ± 62 mmHg*% for RV. GCW was 2100 ± 421 mmHg*% for LV and 322 ± 84 mmHg*% for RV. Those values are comparable to values found in humans  and the volumetric estimated COvol .A linear regression analysis and pearson’s correlation were performed to compare the estimated CO between the three methods Fig. . InvasivThe study at hand is unique in its capability to demonstrate both feasibility and reliability of sophisticated TEE based measurements in anesthetized swine. To the best of our knowledge, this is the first trial to evaluate LV and RV myocardial function and mechanics using the novel none-invasive myocardial work estimation method by Russel and colleagues in this setting. Moreover, our data not only complement porcine standard values that have been determined by others , 30, butThese observations are significant due to the importance of porcine animal models of cardiovascular disease. Swine are frequently chosen as model-organism for cardiovascular disease due to their close resemblance of human anatomy and physiology –5. More 1 and D2 were comparable in swine and humans, while the longitudinal diameter D3 was shorter in swine [Our RV data about TASV and the RVFAC appear to resemble findings in humans , 31. In in swine , 29–32. in swine , the higComparing our data to the porcine TEE study of Huenges et al. we noticed a similar EF in conjunction with half the CO found in our experiments , despitevol and the thermodilution COTD was good as well, but lower than between COPWD and COvol. One possible explanation for the discrepancy between COPWD and COvol is the difficulty to obtain the correct anatomical 2-CH view and the 4-CH leading to underestimated values due to measurements in foreshortened views.Validation of our echo-obtained CO data with an invasively measured reference method  vastly iCertain limitations apply to the results gained in our study. First, study results were obtained in a fairly small sample size of 10 animals. However, choosing a small sample size is particularly desirable from an ethical perspective wherever results are valid. Second, TEE measurements were performed in swine anaesthetized with pentobarbital. Previous research revealed conflicting data on pentobarbital effects on hemodynamics as compared to awake animals –37. HoweCompared to TTE, TEE offers significant advantages in swine: The close anatomic relation of the esophagus to the heart enables high resolution images of the heart. TEE can be applied in the closed chest without significant trauma. This can be paramount in chronic animal experiments. In addition, TEE may be favorable in open-chest models, as it allows for echocardiographic assessment without interfering with surgical interventions. If longitudinal strain values are to be measured, TEE might also be the superior choice over TTE, as apical views may not be achievable using transthoracic echocardiography. However, for the acquisition of longitudinal strain calculation, apical planes are critical , 39.In general, an important constraint in interpretation of conventional strain data is the load dependency , 28. AftTEE offers sufficient morphological, functional and hemodynamic assessment of the heart in swine. The non-invasive GWI may offer an improved assessment of myocardial contractility and mechanics. The established baseline values will inform design and validation of future studies in translational cardiovascular research.


Traditional preclinical echocardiography (ECHO) modalities, including 1-dimensional motion-mode (M-Mode) and 2-dimensional long axis (2D-US), rely on geometric and temporal assumptions about the heart for volumetric measurements. Surgical animal models, such as the mouse coronary artery ligation (CAL) model of myocardial infarction, result in morphologic changes that do not fit these geometric assumptions. New ECHO technology, including 4-dimensional ultrasound (4D-US), improves on these traditional models. This paper aims to compare commercially available 4D-US to M-mode and 2D-US in a mouse model of CAL.n = 12) of mice underwent cardiac magnetic resonance (CMR) imaging to serve as a reference standard. End systolic volume (ESV), end diastolic volume (EDV), and ejection fraction (EF) were compared among imaging modalities. Hearts were also collected for histologic evaluation of scar size (n = 16) and compared to ECHO-derived wall motion severity index (WMSI) and global longitudinal strain as well as gadolinium-enhanced CMR to compare scar assessment modalities.37 mice underwent CAL surgery, of which 32 survived to a 4 week post-operative time point. ECHO was completed at baseline, 1 week, and 4 weeks after CAL. M-mode, 2D-US, and 4D-US were taken at each time point and evaluated by two separate echocardiographers. At 4 weeks, a subset  and EF  4 weeks after CAL when compared to CMR, outperforming 2D-US and M-mode estimations. 4D-US has lower inter-user variability as measured by intraclass correlation (ICC) in the evaluation of EDV (0.91) and ESV (0.93) when compared to other modalities. 4D-US also allows for rapid assessment of WMSI, which correlates strongly with infarct size by histology (r = 0.77).4D-US outperforms M-Mode and 2D-US for volumetric analysis 4 weeks after CAL and has higher inter-user reliability. 4D-US allows for rapid calculation of WMSI, which correlates well with histologic scar size. Echocardiography (ECHO) is a highly efficient and reliable tool for clinical and pre-clinical evaluation of cardiac function –3. AdvanThree-dimensional (3D) ECHO has gained favor recently in clinical and pre-clinical models, allowing full volume visualization of the heart by stacking concentric short-axis images to form a 3D representation at static time points , 11, 12.In this study, we aimed to validate commercially available 4D-US in a mouse model of myocardial infarction. We performed coronary artery ligation (CAL) surgery on mice to evaluate traditional M-mode, 2D-US, and 4D-US using the Vevo 3100 preclinical imaging system against CMR imaging to compare the assessment of volumetric parameters at 4 weeks after CAL.n = 22) and MHC-Cre (−) x Flox-TFAM (n = 15). Both males and females were used in this study. Mice were aged to twelve weeks, at which point they underwent baseline echocardiography followed by coronary artery ligation surgery. Mice were anesthetized and ventilated prior to open thoracotomy through the 4th rib followed by opening of the pericardium and coronary artery ligation (CAL) by suture placement around the proximal coronary artery [All animal use was performed at the University of Pittsburgh in compliance with the National Institutes of Health Guide for Care and Use of Experimental Animals and was approved by the University of Pittsburgh Animal Care and Use Committee. Previously characterized mice harboring a floxed TFAM gene were crossed with a-myosin heavy chain Cre transgene (MHC-Cre) to generate mice that were MHC-Cre (+) x Flox-TFAM (y artery . All surn = 37), 1 week following CAL (n = 32), and 4 weeks following CAL (n = 32). At each timepoint, depilatory cream was applied to the thorax to remove hair. Animals were maintained at 37 °C via heating pad and rectal probe and were monitored using surface ECG limb electrodes throughout imaging. Transthoracic echocardiography was performed using the Vevo 3100 imaging systems  with a probe attached to a step motor. The Visualsonic MX400  linear array transducer was used for all image acquisition. Heart rate was maintained between 400 and 500 bpm during imaging by adjusting isoflurane concentration to a final concentration of 1–2%. M-mode and B-mode images of the heart were obtained for at least ten cardiac cycles in the parasternal long axis and mid-papillary muscle level short axis views. For 4D image acquisition, the step motor was positioned just below the apex and the motor aligned to take concentric short axis images in 0.2 mm steps. At each position, a complete cardiac cycle was recorded using automated ECG and respiratory gating. 4D images were constructed using Vevo 4D image software. Image analysis was performed independently by two blinded sonographers (CR and BM). End-diastolic volume (EDV), End-systolic volume (ESV), and Ejection Fraction (EF), were calculated using the following formulas:Mice were anesthetized using isoflurane delivered by nose cone at the following timepoints: baseline (M-Mode (short-axis):2D-US analysis of the parasternal long-axis was completed using operator-defined LV trace function of Vevo LAB software (v3.2.0) and calculations of EDV, ESV, and EF made by Simpson’s method. 4D-US measurements were calculated directly from volumetric measurements based on operator-defined edge-tracing using Vevo 4D imaging software.The Vevo Strain software was used to measure both longitudinal and radial strain by using long-axis images and semi-automated border tracking. The LV was visualized during end-diastole and the endocardial and epicardial borders were determined. A minimum of five cardiac cycles were then traced automatically by the speckle-tracking software and reviewed by the user. Respiratory variation was excluded from these cycles. Global peak longitudinal and radial strain were calculated using Vevo Strain software on images taken from the long-axis. Global peak circumferential and radial strain were calculated from images from the short axis. Further, the LV was automatically divided into six segments in the long-axis images by the software. The standard deviation of the strain among the individual segments was calculated as a measure of LV dyssynchrony.n = 32). Short axis views were obtained 1 mm, 3 mm, and 5 mm from the apex for standardization. The most distal image was divided into 4 sections and the remaining sections divided into 6 sections as previously described  were anesthetized with 4% isoflurane mixed with room air in an induction box for 1 to 3 min. The depth of anesthesia was monitored by toe reflex, extension of limbs, and spine positioning. Anesthesia was maintained by 1.5 to 2% isoflurane and 100% oxygen via a nose cone. Respiration waveforms were continuously monitored using a small pneumatic pillow under the animal’s diaphragm connected to a magnet-compatible pressure transducer . CMR was performed on a Bruker Biospec 7 T/30 system  with a 35-mm quadrature coil for both transmission and reception. The Bruker Intragate module was used for image-gated cine MRI with retrospective navigation. Subcutaneous injection of Multi-Hance  was administered immediately before the CMR acquisition at 0.1 mmol Gd/kg bodyweight. T1-weighted images to highlight LGE were acquired 15–20 min after the subcutaneous administration of Multi-Hance. Eight T1-weighted short-axis imaging planes covering the whole ventricular volume with no gaps were acquired with the following parameters: Field of view (FOV) = 2.5 cm X 2.5 cm, slice thickness = 1 mm, in-plane resolution = 0.97 μm, flip angle (FA) = 10 degrees, echo time (TE) = 3.059 msec, repetition time (TR) = 5.653 msec. White-blood cine movies with 20 cardiac phases were acquired for each mouse with equivalent temporal resolution for the cine loops was about 16.5–21.5 ms per frame. Eight short-axis imaging planes covering the whole ventricular volume with no gaps and one long-axis plane were acquired with the following parameters: Field of view (FOV) = 2.5 cm X 2.5 cm, slice thickness = 1 mm, in-plane resolution = 0.97 μm, flip angle (FA) = 30 degrees, echo time (TE) = 1.872 msec, repetition time (TR) = 38.293 msec.Mice . The extent of myocardial hemorrhage was defined by dark hypointensity on the cine images. To obtain the proportion of myocardial hemorrhage, the area of hypointensity was manually traced by a blinded operator on the software. The left ventricular endocardium and epicardium boundaries of each imaging slice at the end-systole (ES) and the end-diastole (ED) were manually traced by a blinded operator in the software to calculate the following functional parameters: left ventricular blood volume (LVV), left ventricular wall volume , LV mass, stroke volume (SV), ejection fraction, heart rate (HR), cardiac output (CO), longitudinal shortening, and radial shortening. LVV is calculated by summation of all the short-axis slices. The EF was calculated using the following equation: n = 16) was fixed overnight in 10% formaldehyde at 4 °C. Tissues were then washed with PBS and transferred to 70% EtOH and stored at room temperature. After fixation, tissues were brought to the Department of Pathology Histology Core at the University of Pittsburgh and sectioned into 10 μm slices at 1 mm intervals throughout the myocardium. Sections were stained with hematoxylin and eosin (H&E) or Masson’s Trichrome stains and images obtained on a TissueFAXS Histo  upright brightfield microscope utilizing HistoQuest software. Image analysis was performed by automated red and blue channel separation using Image Measurement 9.0 .LV tissue  except for ICC, which was calculated using Microsoft Excel , and power analysis which was calculated using StataCorp Stata 16.0 .Differences between imaging modalities were evaluated by Bland-Altman analysis and are expressed as % bias and 95% level of agreement (LOA). Bland-Altman percentage bias was calculated as (100*(B-A)/Average vs Average) where “B” represents measurements from 4D-US, 2D-US, or M-mode, and “A” represents measurements from CMR. Intraclass correlation was used to evaluate reliability between single measurements of EDV, ESV, and EF between two users (CR and BM). Normality was assessed using D’Agostino-Pearson omnibus K2 testing for each data set. Regression analysis was performed using Spearman rank correlation to compare scar size among several methods . Global longitudinal strain was calculated throughout the myocardium with average strain − 5.27 ± 1.10% . Spearman rank correlation was used to assess the association of scar size between WMSI, CMR hyperintense regions/LV area, or global peak longitudinal strain to histologic stain assessments , CMR hyperintense volume correlates very strongly , and longitudinal strain correlates strongly . Additional strain measurements, including global radial strain, LV dyssynchrony from long-axis imaging, and both circumferential and radial strain from short axis imaging were also calculated and a full comparison of modalities assessed via Spearman correlation  underwent all imaging modalities.A potential confounder in the study is the use of multiple genotypes on a single background. Specifically, we utilized transgenic mice for the evaluation of volumetric measurements, pooling data from α-MHC-Cre (+) x Flox-TFAM and α-MHC-Cre (−) x Flox-TFAM mice. Because we found no difference between survival, scar size, baseline and 4-week EDV, ESV, or EF between groups  x Flox-TFAM and α-MHC-Cre (−) x Flox-TFAM mice were compared at baseline and Week 4 following CAL by 4D-US, 2D-US, and M-mode and demonstrate no significant changes by any modality when comparing EDV, ESV, and EF.Additional file 3: Table S1. Comparison of ESV, EDV, EF, Scar Size, and survival between transgenic groups.Additional file 4: Table S2. Spearman Correlation Values and p-Values Between Modalities for Assessing Scar Size. Histologic Sections, WMSI from 4D-US, Hyperintense Tissue on CMR, Longitudinal Strain, Long Axis Radial Strain, Long-Axis LV Dyssynchrony, Short Axis Radial Strain, and Short Axis Circumferential Strain are compared to each other modality


Although hypertrophic cardiomyopathy (HCM) is considered a disease of the left ventricle (LV), right ventricular (RV) abnormalities have also been reported on. Cardiovascular magnetic resonance feature tracking (CMR-FT) accurately and reproducibly quantifies RV myocardial deformation.To investigate RV deformation disorders in childhood HCM using CMR-FT.Consecutive subjects aged <18 years with echocardiographic evidence of HCM were enrolled. Cardiovascular magnetic resonance (CMR) was performed including RV volumetric and functional assessment, and late gadolinium enhancement (LGE) imaging.We included 54 children  with HCM, of which 28 patients  had late gadolinium enhancement. LV outflow tract obstruction (LVOTO) was detected in 19 subjects (35.2%). In patients with LVOTO, RV global longitudinal strain (RVGLS) , RVGLS rate , RV radial strain (RVR)  and RVR rate  were lower than in patients without LVOTO. The RVR rate (p<0.01) was lower in patients with LGE in comparison to patients without LGE.Children with HCM, especially with LVOTO, have significantly reduced indices of RV mechanics despite normal RV systolic function. It seems that the degree of LVOT obstruction is responsible for compromising the RV dynamics, rather than either mass or the amount of LV fibrosis. Hypertrophic cardiomyopathy (HCM) is one of most common primary myocardial diseases in children, which can be characterized by massive myocardial proliferation, vast fibrosis and life-threatening prognosis , 2. Althcine sequences without the need for additional tagged images  in the absence of hemodynamic conditions that could account for the observed hypertrophy [CMR was performed on a 1.5-T scanner . For volumetric and functional assessment electrocardiogram-gated, breath-hold, steady-state free precession cine images were acquired in standard orientations with a segmented k-space steady-state free-precession technique, using 25 phases per cardiac cycle. Late gadolinium enhancement (LGE) images were obtained in long-axis and short-axis imaging planes with a breath-hold segmented inversion recovery sequence performed 10–15 min after intravenous administration of 0.1 mmol/kg of gadobutrol .Steady-state free precession (SSFP) images served for the calculation of ventricular volumes and ejection fraction with the use of dedicated software . Manual delineation of endocardial and epicardial contours was performed in end-diastolic and end-systolic phases. LV (LVEDV) and RV (RVEDV) end-diastolic volumes, LV (LVESV) and RV (RVESV) end-systolic volumes, LV (LVSV) and RV (RVSV) stroke volumes and LV (LVM) mass, as well as left (LVEF) and right (RVEF) ventricular ejection fractions were calculated. All volumetric parameters were indexed to the BSA. The papillary muscles were each time excluded from the LV mass calculation. The presence of left ventricular LGE was initially determined using visual assessment by two independent experienced observers and if positive, quantified. Quantification was performed with QMass v7.6  software as a signal intensity threshold of >6 SD above remote myocardium (>6 SD LGE). The extent of LGE was presented as the percentage of total LV mass.RV myocardial feature tracking analysis was performed based on the acquired b-SSFP cine images using a dedicated software . The global right ventricular longitudinal peak strain (RVGLS) and global longitudinal peak strain rate (RVGLS rate) parameters were obtained from a 4-chamber view. Peak circumferential and radial strain and strain rates parameters  were determined in short axis view at the basal and mid-ventricular section of the ventricle. Because of the known tendency for artefacts and lower muscle thickness in the peri-apical slices, these slices were not included in the CMR-FT analysis. The basal slice in short axis view was defined as the first slice below the atrioventricular level showing a complete myocardial enclosing. The mid-ventricular slice was localized at the level of left ventricular papillary muscles. Endocardial and epicardial contours were drawn manually twice for each patient by two independent and skilled operators. Values of peak circumferential and radial strain and strain rates obtained in each slice of RV were averaged .p-value of less than 0.05 was considered to indicate statistical significance. Statistical analyses were performed with the use of MedCalc 12.1.4.0 software .All continuous variables were expressed as mean ± standard deviation (SD) or as median and interquartile range and were tested for normal distribution with the use of the Kolmogorov–Smirnov test. Comparisons between groups were performed using the Student’s t-test or Wilcoxon-Mann-Whitney U test for continuous variables, and chi-square or Fisher exact test for categorical variables as appropriate. Correlation analysis was performed using the Pearson’s method. Intra- and interobserver variability were evaluated using the Bland-Altman test and expressed as bias ± SD  and intraclass correlation coefficients (ICCs), and the coefficient of variation (CoV). A two-sided The study cohort comprised 54 children  with HCM, of which 30 (55.6%) children had family history of HCM. There was no hypertrophy of RV free wall found in the studied cohort. In the study group 19 subjects (35.2%) had LVOT obstruction (LVOTO). Expectedly, children with LVOTO were older than children without LVOTO . There were no differences found in terms of right ventricular volumes and right ventricular ejection fraction (RVEF) between children with obstructive vs non-obstructive HCM .The RV longitudinal and radial strain and strain rate parameters varied depending on the presence of LVOT obstruction. In patients with hypertrophic obstructive cardiomyopathy (HOCM) the values of RVGLS , RVGLS rate , RVR  and RVR rate  were significantly compromised when compared with subjects without LVOTO. The presence of LVOTO did not change the values of RV circumferential strain and strain rate (p = ns). The comparison of the indices of RV strains and strain rates in subjects with and without LVOTO is presented in As previously published , LGE wasFurthermore, we found a negative correlation between RV radial strain and strain rate, and the degree of hypertrophy measured with LVMI (RVR p = 0.04 and RVR rate p < 0.01) . Also, RThe indices of reproducibility for right ventricular strain and strain rate parameters analysis were satisfactory—intraobserver and interobserver ICCs ranged between 0.83 and 0.99 for all RV components of myocardial performance .This is the first study to describe in detail cardiovascular magnetic resonance—derived right ventricular longitudinal, circumferential and radial strain and strain rates in children with hypertrophic cardiomyopathy and to relate these parameters to LVOT obstruction and fibrosis assessed with late gadolinium enhancement. We demonstrated that there was a substantial reduction in RV displacement parameters in obstructive childhood HCM as compared to non-obstructive childhood HCM. Also, few indices of RV mechanics were decreased in children with LGE in comparison to children with HCM and no fibrosis on CMR.Over the last 50 years, awareness regarding the characterization of HCM has evolved dramatically in terms of phenotypic expression, pathophysiology, and clinical course –21. It iCMR is a reference standard method for evaluating RV function for diagnostic, prognostic, and therapeutic implications. The excellent signal-to-noise ratio between the myocardium and the blood pool allows for reliable volumetric analysis without geometric assumptions. CMR-FT has been a new less demanding technology for quantifying ventricular mechanics in comparison to the tagging technique . It has The data on RV deformation assessed by CMR-FT in adult HCM population are very limited, and no such work has been performed in childhood HCM. In an echocardiographic study, Cincin et al. reported significant impairment of RV function and 2D-STE-based strain of the RV free wall basal segment in HCM adults in comparison to control subjects . MoreoveThe limitations of our study are mostly inherited by its design. This is a retrospective study with a relatively small sample size. It must also be noted that the study was conducted over an extended period of time, and there has been advancement in CMR technology. For example, while mapping techniques are now important to the diagnosis of HCM, they were not applied to our cohort. Large, prospective, multicentre studies are needed to validate our results and to provide further evidence that RV dysfunction is associated with a disease state and poor prognosis of HCM in young subjects.This work helps to better understand the RV malfunction in HCM children. All indices of RV myocardial mechanics in HCM juveniles were globally compromised when LVOTO was also present. Moreover, the degree of LVOT obstruction, rather than fibrosis, appeared to be a factor associated with the reduction of RV mechanics.S1 Data(XLSX)Click here for additional data file.


Dear editor In a recent issue of the journal, Dastani et al. (2019)The most critical flaw of the article was the duration of supplement therapy which was about 5 days and the related complications such as heart failure, myocardial infarction, the rate of cardiopulmonary resuscitation, and the mortality rate were measured after this duration which we know is too short and it cannot show the complications and supplemental effect properly. It is important to know that heart failure and related complications are mostly chronic conditions and it is not accurate to claim that it is measurable in such a short time. Furthermore researchers didn’t assess blood pressure, atrial fibrillation, valvular heart disease, alcohol use and smoking in patients which can all change the structure and function of heart and can relate to heart failure  in the study so it may not show proper effect.Furthermore, duration of the intervention in this study was determined without reason and logic and the authors didn’t mention any references.The authors have declared that there is no conflict of interest.


In Cox analysis, LAS , p = 0.001), LVSI  and LGE+ , p < 0.0001) were independent predictors for MACEs. In a 4-point risk scoring system based on LV ejection fraction (LVEF) < 30%, LGE+, LAS > −7.8% and LVSI > 0.48%, patients with 3 and 4 points had a significantly higher risk for MACEs. LAS and LVSI are independent predictors of MACEs and provide incremental value beyond LVEF and LGE+ in patients with NIDCM and myocardial fibrosis.To investigate the relationship between left ventricular (LV) long-axis strain (LAS) and LV sphericity index (LVSI) and outcomes in patients with nonischemic dilated cardiomyopathy (NIDCM) and myocardial replacement fibrosis confirmed by late gadolinium enhancement (LGE) using cardiac magnetic resonance imaging (cMRI), we conducted a prospective study on 178 patients  with first NIDCM diagnosis. The evaluation protocol included ECG monitoring, echocardiography and cMRI. LAS and LVSI were cMRI-determined. Major adverse cardiovascular events (MACEs) were defined as a composite outcome including heart failure (HF), ventricular arrhythmias (VAs) and sudden cardiac death (SCD). After a median follow-up of 17 months, patients with LGE+ had increased risk of MACEs. Kaplan-Meier curves showed significantly higher rate of MACEs in patients with LGE+ ( Nonischemic dilated cardiomyopathy (NIDCM) is the most common primary myocardial disease, being characterized by left ventricular (LV) enlargement and global systolic LV function impairment in the absence of ischemic heart disease (IHD), hypertension or valve disease . Due to While current guidelines recommend echocardiography as the first line of investigation in patients with NIDCM ,5, it caThe aim of this study was to investigate the relationship between cardiac remodelling process and MACEs, and if it increases outcome prediction beyond LGE, in patients with NIDCM.2; both cMRI-determined. The exclusion criteria are represented by (1) IHD, other cardiomyophaties, significant valvular and congenital heart disease ; (2) contraindications to cMRI ; (3) refusal to participate in the study , and current medication; biomarkers and 12-lead ECG. 24-h Holter monitoring, transthoracic echocardiography and cMRI were performed. The current research was approved by the Ethics Committee of the Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca—decision number 280/26.07.2018. The study was conducted in accordance with the principles of the Declaration of Helsinki. All patients were informed about the investigation protocol and signed a written consent form.All cMRI images were ECG-gated and were acquired during apnoea with a 1.5 T magnetic resonance (MR) scanner . A standard scanning protocol that was in accordance with current international guidelines was used . The acq3) [Image analysis: All images were evaluated by two experienced observers, blinded to all clinical data. LVEDV and LV end-systolic volume (LVESV), LVEF and end-diastolic LV mass (LVM) were measured on short-axis cine-SSFP images. Epicardial and endocardial borders were traced semi-automatically at end-diastole and end-systole using specialized software . The maximum left atrium (LA) and right atrium (RA) volumes were measured in all patients from the four-chamber view. All volumes were indexed to body surface area. Tricuspid annular plane systolic excursion (TAPSE) was measured from the mid-four-chamber cardiac view to assess right ventricular (RV) longitudinal motion. LV longitudinal function was assessed by LAS, defined as the difference in mitral annular displacement at end-systole vs. end-diastole, and expressed as a percentage . LVSI wa3)  , and HF requiring hospitalization defined accordingly to current international guidelines ,5. Hospi2 test or Fischer exact test as appropriate  and Wilcoxon signed rank test (continuous data). The hazard ratio (HR) for the prediction of events was calculated using a Cox regression model. For each outcome, we considered all of the significant variables in the univariate analysis and sought the best overall multivariate models for the composite end-point, by stepwise-forward selection, with a probability to enter set at p < 0.05 and to remove the effect of regression at p < 0.05. Event-free survival was generated by the Kaplan–Meier method and statistical significance was determined by the log-rank test. Multivariate analysis was performed by constructing a multiple logistic regression model, including the HR (95%CI) calculation. Cohen’s Kappa inter- and intra-observer coefficient calculation was performed. Retrospective test power calculation and prospective sample size were estimated, with type I and type II variation according to sample size. The statistical analysis was performed using the MedCalc .All data were tested for normality using the Kolmogorov-Smirnov test. Data were presented as median, mean ± standard deviation (SD) or percentage. Baseline characteristics among those with and without LGE patients with clinical outcomes were compared by Chi-square χn = 64, 36% vs. n = 114, 64%). The baseline characteristics are presented in A total of 178 patients  met the enrolment criteria . They wep < 0.001) and many more of these had LVEF < 30% . The LGE+ group presented with increased LVM index ≥ 92 g/m2 (p = 0.01), LVEDV ≥ 145.5 mL/m2 (p < 0.001), LVSI ≥ 0.43 (p < 0.001) and reduced LAS < −7.8% (p < 0.001).At admission, 54 (30.3%) presented with dyspnoea, 28 (15.7%) with palpitations and 18 (10.1%) had history of syncope. LGE+ patients had significantly increased LV end-diastolic filling pressures , HF requiring hospitalization (n = 11), and SCD (n = 6). The patients with VA were majority males, had increased LVESV , decreased LVEF , increased LGE mass  and LVSI . Of them, ten received ICD therapy and 4 were ablated due to implantable cardioverter defibrillator therapy refusal, the last had a mean LVEF around 30%, two of them had NIDCM post-myocarditis and two were idiopathic NIDCM. The incidence of MACEs was significantly higher in the LGE+ group vs. the LGE− group . The Kaplan-Meier curves for event-free survival showed a significantly higher rate of MACEs in patients with LGE+ , p < 0.001), high LVSI , p < 0.01) and decreased LAS , p < 0.001) , 31 patients (17.4%) experienced MACEs: VA (< 0.001) .p < 0.0001), reduced LAS , p < 0.001) and increased LVSI , p < 0.001) and LGE mass , p < 0.001) , < 0.001) .p < 0.0001)  . Howeverp < 0.0001)  . We obseThis prospective study is the first to evaluate the association between cMRI-based LV geometry and strain and outcome, in a significant, well-diagnosed NIDCM cohort. LAS and LVSI were independent predictors of MACEs in patients with NIDCM and myocardial replacement fibrosis. These findings were independent of LVEF and other established prognostic factors in a multivariable analysis. We also demonstrated that the addition of both LAS and LVSI to LVEF and LGE was superior for the prediction of MACEs over those based only on LVEF and LGE. The incidence of MACEs was higher in those with myocardial replacement fibrosis and altered LV geometry and strain, therefore representing a group who may require more aggressive therapy and rigorous follow-up.NIDCM is typically associated with LV mid-wall replacement fibrosis, which worsens its prognosis ,22. Furtp < 0.001), similar with other published data. In patients with NIDCM, LVSI was initially evaluated in 2- and 3-dimensional echocardiography-based studies, which demonstrated that it was an independent predictor of MACEs, having a significant long-term prognostic impact [In our study, we confirmed the role of LVSI in predicting MACEs with a cut-off value of >0.43 (c impact ,27. Furtc impact ,29, whilc impact . Moreovec impact . TherebyFurthermore, we demonstrated that LAS, a myocardial strain parameter, was an independent predictor for outcome in patients with NIDCM. cMRI-based myocardial strain has proved its utility in early diagnosing and predicting various cardiac diseases. In patients with myocardial infarction, Gjesdal et al. showed that LAS was progressively reduced in larger mitral insufficiency and was associated with the infarction mass , while SThe role of LVEF and LGE as independent predictors of MACEs in patients with NIDCM has been confirmed by recently published data. To our knowledge, only two studies have approached our goals, namely Kano et al. identified that the addition of LVSI to LGE significantly increased prognosis of MACEs , while RBased on these four parameters, we were able to create a risk stratification scoring system. Hitherto, a single study created a similar scoring system based on LAS, LVEF and LGE+ which provided significant predictive value . We demoStudy limitations: Firstly, we conducted a single centre study. Secondly, we were unable to acquire T1 mapping sequences, and therefore extracellular volume and diffuse myocardial fibrosis could not be quantified. Additionally, the follow-up was, relatively speaking, not very long.cMRI parameters of geometry and longitudinal strain, namely LVSI and LAS, are independently associated with increased risk of MACEs in NIDCM patients with myocardial replacement fibrosis confirmed by cMRI-LGE. For the first time, we demonstrate that the combined usage of LVSI and LAS provide incremental value beyond the assessment of LVEF and LGE in outcome prediction. These findings have potential therapeutic implications regarding the management of patients with NIDCM.


The conventional orthotopic heart transplantation (OHT)  results in atrial enlargement. The variability of atrial size and function in these patients has not been previously reported.1. Determine the variability in the post-OHT size and function of left and right atria; 2. Analyze the relationship of donor and native atria; 3. Compare cardiac MRI (CMR) with transthoracic echocardiogram (TTE).This is a retrospective observational study. Nine patients who had undergone OHT via biatrial anastomosis technique and had both CMR as well TTE within one month of each other were selected. Using the optimized apical 4-chamber views in both TTE and CMR cine images (SSFP), endocardial borders of the native and donor, right atrial (RA) and left atrial (LA) free wall and septum were traced from base to the valvular annulus and areas were determined in late systole when atrial volumes are maximal and late diastole when atrial volumes are minimal. RA and LA function was assessed quantitatively using percentage of change in cavity area or fractional area change (FAC). FAC was defined using the formula ([end-systolic area] - [end-diastolic area])/[end-systolic area] × 100). Native and donor areas were also combined to calculate the total area of the right and left atria. Comparison was made between the TTE and CMR values. Data for continuous variables are expressed as mean value +/- SD.See Tables Left atrial volumes consistently predict outcome in most patient groups studied. LA size is frequently severely distorted after OHT and is dependent upon extent of retained pulmonary vein cuffs or associated donor lung preparation, individual cardiac surgeon preferences, and cardiac recipient organ status. Knowing the variations in atrial sizes may provide a new avenue for clinical investigation Figure . A CMR aIt appears that the retained native atrium does not contribute to atrial contraction. This resulted in a negative total FAC% in 45% (4/9) of our patients. Given the large retained native atria, and its poor contribution to atrial contraction, this report suggests that minimizing this atrial reservoir may be valuable and warrants additional study. The underestimation of native atrial size reported by TTE is most likely due to apical fore-shortening of the true long-axis and the far field ultrasound imaging.This observational study suggests that despite a generally reasonable correlation between TTE and CMR measures of OHT atria, significant differences exist. Furthermore, because of suspected intra-atrial (donor versus native) mechanical dysynchrony, some patients surprisingly had a negative FAC% suggesting that the native atria is larger during donor atrial contraction – acting as a non-functioning reservoir. The association of this to the clinical outcome has yet to be determined.


A previously validated multi-stage echocardiography (echo) classification algorithm for diastolic function (DF) showed that severe diastolic dysfunction independently predicts mortality after acute myocardial infarction. Currently, echo is the non-invasive imaging modality of choice for classifying diastolic dysfunction into four distinct groups based on a combination of echo parameters. However, a newer multi-stage echo algorithm has been developed that classifies patients into three diastolic function categories: Normal, Abnormal Relaxation, and Severe . This algorithm is a validated systematic approach that provides accurate diastolic function staging of patients, and it has been shown to correlate strongly with catheter derived left ventricular filling pressures. It is currently unknown whether CMR can accurately categorize the overall severity of diastolic dysfunction using a similar multi-stage approach.A CMR multi-stage diastolic function classification system, adapted by substitution of CMR-derived parameters for corresponding echo parameters, can accurately classify diastolic dysfunction severity. Furthermore, applying this diastolic dysfunction algorithm can facilitate evaluation of the relationship between diastolic function and CMR infarct size.Subjects (n = 51) underwent CMR for characterization of left ventricular mass, left end diastolic volume, left atrial volume, ejection fraction, mitral inflow pattern, tissue velocities, and infarct size within 2.8 ± 1.4 days status post acute myocardial infarction. A subset of patients (n = 21) concurrently had echo within 2.3 ± 1.6 days of the CMR. CMR and echo data were used independently to classify subjects' diastolic function as Normal, Abnormal Relaxation, or Severe, using the multi-stage approach. The algorithm uses ejection fraction, pulmonary vein inflow, mitral inflow patterns, and deceleration time to initially categorize patients' diastolic function. If the initial parameters did not clearly delineate the appropriate classification, tissue velocity imaging, including E/E' ratios, was used to further differentiate between the three groups. Myocardial infarct sizes obtained by CMR were then compared between the resulting categories.The severity of diastolic dysfunction using echo n = 21) and CMR (n = 51) showed a strong relationship with acute myocardial infarction size . The correlation between individual parameters by echo and CMR was only fair (Table  and CMR Correlation of single parameters of diastolic dysfunction between echocardiography and CMR is only fair. This lack of agreement is likely related to the temporal separation between the imaging studies and the rapidly evolving changes following acute myocardial infarction. However, using the multi-stage classification algorithm provides improved agreement, and this system is very sensitive for diagnosing diastolic dysfunction, especially when severe. Lastly, there is strong association between acute myocardial infarct size and severity of diastolic dysfunction Figure .Figure 1


Definite diagnosis of cardiomyopathy types can be challenging in end-stage disease process. New growing data have suggested that there is inconsistency between echocardiography and pathology in defining type of cardiomyopathy before and after heart transplantation. The aim of the present study was to compare the pre-heart transplant echocardiographic diagnosis of cardiomyopathy with the results of post-transplant pathologic diagnosis.P < 0.001). On the other hand, in 24 patients, the results of echocardiography as regard to the type of cardiomyopathy were inconsistent with pathologic findings.In this retrospective cross-sectional clinicopathological study, 100 consecutive patients have undergone heart transplantation in Masih-Daneshvari hospital, Tehran, Iran, between 2010 and 2019. The mean age of patients was 40 ± 13 years and 79% of patients were male. The frequency of different types of cardiomyopathy was significantly different between two diagnostic tools (echocardiography versus pathology, Based on the findings of the present study, it could be concluded that there is a significant difference between echocardiographic and pathologic diagnosis of cardiomyopathy; therefore, it is necessary to use additional tools for definite diagnosis of cardiomyopathy like advanced cardiac imaging or even endomyocardial biopsy before heart transplantation to reach an appropriate treatment strategy. Heart transplantation (HT) is a surgery in which a donor heart is transplanted to a selected recipient with advanced refractory heart failure. HT is referred as the final treatment strategy of end-stage heart failure (HF) in some cases, when none of the medical therapies are effective .As well, cardiomyopathy (CMP) is a disease of the heart muscle that directly affects and also multiple etiologic factors might be contributing, the most common are coronary artery disease, poorly controlled hypertension, toxins , valve diseases, infections , inflammatory diseases, and even genetic alterations  .According to the WHO classification for cardiomyopathies, this disease is divided morphologically into dilated, hypertrophic, and restrictive types. The most common type is dilated and its prevalence reaches to 36.5 in 100,000 population, while the restrictive type is the least common . The morThe prevalence of heart failure is increasing and one of the most important causes is coronary artery disease , 7. HoweEchocardiography, cardiac magnetic resonance imaging (CMR), and endomyocardial biopsy are known as choice diagnostic methods used for diagnosis and assessment of various cardiac diseases like myocarditis and some forms of infiltrative cardiomyopathies. Each of these methods has its advantages and drawbacks and their efficacy varies according to different cardiac diseases , 14. How.Up to the present time, no accurate diagnostic algorithm has been developed for definite diagnosis of cardiomyopathy , and theIn this retrospective cross sectional study, a total of 100 candidates for heart transplantation who admitted to the heart transplant department of Masih Daneshvari hospital, Tehran, Iran, in 2010–2019, were selected. All heart transplant candidates referred from other hospitals around the country to our center and had previous multiple hospitalization in years before candidacy and had refractory heart failure symptoms with maximal pharmacological and guideline-directed device therapy and had a complete assessment by experienced heart transplant team with appropriate pretransplant tests and imaging studies  as indicated. All patients that were not bedridden and inotropic-dependent in the hospital did cardiopulmonary exercise testing, and in no eligible case, we had VO2 max more than 10 ml/kg/min. Demographic, clinical, and paraclinical data of patients with focus on the diagnosis of cardiomyopathy before  and after (based on pathologic findings of the explanted heart) heart transplantation were collected from electronic medical records and was reviewed by two experienced cardiologists of the heart transplant team and pretransplant clinical diagnosis was made by them. Post-transplant anatomopathological diagnosis was performed by a cardiovascular pathologist who was unaware of clinical diagnosis and consisted of macroscopic and microscopic study. The explanted hearts were fixed in buffered formalin. Standard samples were taken from the two ventricles , septum, coronary vessels, and valvular system. Histological 5-micron-thick sections and routine staining  were performed. In selected cases, special dyes (e.g. Congo red and thioflavin in patients with suspected amyloidosis) and inmumohistochemical techniques  were employed. The histological diagnosis of myocarditis was made according to the Dallas criteria. The study protocol was approved by the Ethical Committee of Shahid Beheshti University of Medical Sciences (Committee’s reference number: IR.SBMU.NRITLD.REC.1396.398) and informed consent was obtained from all participants before entering the study.Z-test. As well as this, χ2 test was used for testing relationships between categorical variables. Statistical significance was considered when the P value was < 0.05.The software SPSS 25 package  was used for statistical calculations and data analysis. Data are expressed as mean ± standard deviation (SD). The normality of data was assessed by Kolmogorov-Smirnov The mean age of patients was 40 ± 13 years and 79% of patients were male. Ninety-five percent of patients had normal sinus rhythm in ECG and 49% showed an LBBB pattern. We observed that 38% of individuals had intracardiac devices (36% implantable cardioverter defibrillator (ICD)/2% cardiac resynchronization therapy (CRT)) and the mean weight of explanted heart was 438 ± 130 g. Positive history of coronary artery bypass surgery (CABG), percutaneous coronary intervention (PCI) with coronary stents, and heart valve replacement was seen in 5, 6, and 4% of patients, respectively. All the patients had complete detailed transthoracic echocardiography before transplant often multiple by an experienced echocardiologist and transesophageal echocardiography as needed. In echocardiography mean pretransplant LVEF in our cases was 12.27% and 100% showed evidence of RV systolic dysfunction according to 2015 ASE guidelines for cardiac chamber quantification by echocardiography in adults . We deteP < 0.001). In 24 patients, the results of echocardiography as regard to the type of cardiomyopathy were not a match with pathologic findings. The frequency of different types of cardiomyopathy including DCM, ischemic CMP, valvular CMP, amyloidosis, hypertrophic CMP, and myocarditis in echocardiography assessment was 69, 24, 1, 0, 1, and 5%, respectively. This frequency in pathologic assessment was 57, 27, 4, 1, 1, and 10%, individually (Table As is shown in Table ly Table .Table 3Twelve cases that clinically diagnosed DCM regarding echocardiographic data after pathologic evaluation reclassified in other groups. The most discrepancy between echo versus pathology was observed in myocarditis category that we know DCM is the final consequence of chronic unresolved myocarditis and highlights the importance of pretransplant endomyocardial biopsy and CMR or additional serologic assays for better etiologic classification. All patients that had a remote history of surgical heart valve replacement reclassified in valvular CMP by pathologic diagnosis though their echocardiographic diagnosis was compatible with DCM.Obviously, cardiomyopathy causes low cardiac output and/or elevated intracardiac pressures at rest or during stress that lead to heart failure. Heart transplantation is an accepted treatment for patients who are in the end-stage of heart failure . Apart fOur findings are in accordance with previous studies , 12, 19.Etiologic diagnosis in patients with end-stage cardiomyopathy can be challenging. In these cases, accurate diagnosis of patients before transplantation is critical and has priority to heart transplantation. Accurate diagnosis of patients before transplantation lead to proper treatment and subsequently slow down disease progression and improve patient outcome in particular diseases including sarcoidosis, myocarditis, iron toxicity-associated cardiomyopathy, and others. Moreover, it is important to accurately diagnose patients with diseases such as sarcoidosis, amyloidosis, and particular types of myocarditis due to the recurrence in the transplanted heart . AlthougIt is logical to expect that endomyocardial biopsy cannot be performed in early steps of cardiomyopathy diagnosis, but some convincing data exist which strongly support the role of endomyocardial biopsy in providing additive information besides echocardiography in a definite diagnosis of cardiomyopathy . DiagnosIn summary, based on the findings of the present study, it could be concluded that there is a significant discrepancy between echocardiography and pathology in the diagnosis of cardiomyopathy; therefore, it is required to accurate diagnosis of cardiomyopathy with new advanced cardiac imaging like CMR and detailed genetic and serologic assays and pathologic assessment to reach an appropriate treatment strategy. Additional robust studies in different populations with larger sample sizes are essential to confirm these data.


Several studies demonstrate the relationship between coronary artery disease and inflammatory parameters. Nevertheless, there is paucity of data regarding the role of high sensitivity (hs)-C-reactive protein (CRP) to albumin ratio (CAR) in patients with ischemia on gated single photon emission tomography (SPECT) myocardial perfusion imaging (MPI). This study was aimed at demonstrating the relationship between CAR and the occurrence of ischemia on gated SPECT MPI.We retrospectively evaluated 2.048 referred patients for gated SPECT MPI from a cardiology outpatient clinic between October 2017 and June 2019. After applying exclusion criteria and measuring serum CRP and albumin levels, we included 126 patients in the study. We then classified subjects into different groups according to the absence or presence of ischemia on gated SPECT MPI.According to laboratory findings, hs-CRP and CAR were significantly higher in the ischemia group, while the serum albumin was significantly lower in ischemia group (p<0.05 for each). The independent predictors of presence of ischemia in multivariate analysis were hypertension and CAR . The optimal value of CAR for presence of ischemia was 0.96 with 76% sensitivity and 71% specificity.We found CAR values as a predictor for ischemia before MPI. In daily practice, many patients with chest pain and similar cardiac complaints are evaluated in outpatient clinics. Appropriate patients are oriented to perform stress electrocardiography, stress echocardiography, or gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) to investigate myocardial ischemia. In addition, MPI is known to evaluate the prevalence and severity of myocardial ischemia ,2.Inflammatory process has an important role in atherosclerosis, plaque development, and plaque progression. High-sensitivity C-reactive protein (hs-CRP), neutrophile count, lymphocyte count, monocyte count, and albumin are the most studied and clinically evaluated inflammatory markers ,4. InflaWe retrospectively evaluated 2048 patients referred for gated SPECT MPI from a cardiology outpatient clinic between October 2017 and June 2019. Out of these, we enrolled patients with serum CRP and albumin levels measured one day before MPI. After applying exclusion criteria, we included 146 patients in the study. We contacted patients through telephone to obtain cardiovascular risk factors and diseases that might affect acute phase reactants. We further excluded participants having a history of CAD (with revascularization), chronic kidney disease (estimated glomerular filtration rate <60 mL/dk), hepatic disease , history of cancer or systemic inflammatory disease, patients taking statins, anti-inflammatory drugs, or antibiotic medications within one week from the study. Finally, we had 126 eligible patients for the analysis . The nucWe performed a two-day stress/rest imaging protocol using Technetium 99-m methoxy-isobutylisonitrile (Tc-99m MIBI) in order to evaluate myocardial perfusion. During peak exercise, we injected radiopharmaceutical agents on modified Bruce protocol or at peak hyperemia. For stress imaging, we used dipyridamole (0.142 mg/kg/min) or adenosine (0.28 mg/min) infusion as a radiopharmaceutical agent. Imaging began 30-45 min after injecting 15-20 mCi Tc-99m MIBI. We injected a similar dose for rest imaging if there was any suspected perfusion defect on stress images.We obtained all images over a 180° angle orbit from right anterior oblique, 45° angle to left posterior oblique, 45° angle using a dual-head γ-camera  equipped with ultra-high resolution collimator, 64x64 matrix, an elliptic orbit with step and shoot acquisition at 3° intervals over 180° angle, 60 projections and 9-13 s per projection using a 20% energy window centered on the 140 keV photopeak of Tc-99m. The patients lay in supine position on the surface with their arms raised straight above the head. Image sets obtained by SPECT analysis were reconstructed on a dedicated workstation  using WBR and Evolution for Cardiac recommended manufacturer relative risk and noise reduction parameters, with and without CT based AC (12 iterations and 10 subsets). At the end of each acquisition, a single low-dose CT scan  of the chest was performed to obtain attenuation maps automatically applied by the processing software in order to correct the emission data. The MPI dataset was carefully re-matched with the CT attenuation map to produce the attenuation corrected images.We performed routine blood chemistry measurements including hs-CRP (mg/L) in the morning. In addition, we measured albumin and hs-CRP levels using Roche Diagnostics Cobas 8000 analyzer. We deduced the CAR (mg/g) value by dividing hs-CRP level to albumin level, and results were obtained from the same blood samples.We performed overall analysis using Statistical Package for Social Sciences . We described continuous variables as mean ± standard deviation or median values, while categorical variables as frequencies and percentages (%). We verified the normality of continuous variables using Kolmogorov-Smirnov statistics. Meanwhile, we performed Mann-Whitney U test and independent t-test to evaluate parametric variables. We used χ2-test or Fisher’s Exact test to evaluate categorical variables. Statistical significance was set at p<0.05. The variables that showed marginal association in univariate analysis were moved to multivariate logistic regression analyzes. We performed multivariate logistic regression analyzes to obtain independent predictors of ischemia in MPI. The receiver operating characteristics curve analysis was used for calculating the CAR value that predicts presence of ischemia with the best possible specificity and sensitivity.All participants in the study underwent gated SPECT MPI. The mean age of participants was 59.8±11.3 years and 56 patients (44%) were male. The subjects were classified into groups according to the absence or presence of ischemia on gated SPECT MPI. In this study, we evaluated the association between CAR and MPI detected ischemia in patients with stable CAD. Among various inflammatory parameters, CAR showed the best capability to discriminate myocardial ischemia detected by MPI. This association was independent of other predictors.Hs-CRP is considered to be an independent cardiovascular event marker used in cardiovascular risk classification, and in some scores like Reynolds score, hs-CRP is present ,10. RedbThere is an ongoing debate on whether hs-CRP is an indicator of inflammation or whether it contributes to the development of atherosclerosis . In atheAlbumin is known as an acute phase marker with reduced levels in cases of infection and chronic inflammation. Low albumin levels are known to have prognostic significance in cases such as acute coronary syndrome, heart failure, and stable coronary heart disease . HypoalbIt is well-known that inflammatory reactions take place in all stages of myocardial ischemia. In ischemic myocardial tissue, pro-inflammatory chemokines are strongly secreted thereby activating leukocytes leading to leukocyte migration to the inflammation area. A growing set of clinical evidence suggests that neutrophil-to-lymphocyte ratio (NLR), CRP, albumin, and lymphocyte are easily accessible and cheap markers to assess inflammation, especially in acute coronary syndromes . NLR wasSeveral reports show that the severity and extent of myocardial ischemia can be determined accurately using SPECT MPI; they have also highlighted the prognostic value of this method. Spectral perfusion screening has been reported to have lower CRP levels in patients with normal myocardial functions than with myocardial ischemia .The CAR is a marker that is calculated by the ratio of these acute phase markers; and is believed to be more sensitive in predicting inflammatory events. In some CVD (such as stable angına pectoris and acute coronary syndromes), CAR values were higher than in control groups and disease severity was associated with CAR values ,8,9. In Although CRP and albumin are both acute phase markers, there is experimental evidence that demonstrates the presence of CRP in atherosclerotic lesions. The exertion and measurable values of these markers vary slightly in patients with ischemia due to myocardial ischemia in daily life efforts. Our study is a novel one which investigates the relationship between myocardial ischemia and CAR values. Therefore, CAR values at any time in patients with stable CAD may be predictive for ischemia detection in outpatient clinics.Owing to the retrospective nature of this study, we could not assess myocardial viability by MPI, and hence could determine the ischemia percentage from MPI reports.CAR is an independent variable in detecting myocardial ischemia in stable CAD patients. CAR values can be used to predict the presence of ischemia prior to invasive procedures in daily in daily practice.


A 22-year-old man presented with severe left ventricular (LV) dysfunction and progressive heart failure. The 12-lead electrocardiogram showed short runs of supraventricular tachycardia suggestive of focal atrial tachycardia. The patient underwent successful radiofrequency ablation. There was a complete recovery of symptoms and LV function at six months of follow-up. We discuss the importance of identifying tachycardiomyopathy as a reversible cause of heart failure. All patients presenting with heart failure should undergo a diligent search for the underlying etiology . This evIn the present case, a young man presented with recent-onset heart failure and was initially diagnosed to have dilated cardiomyopathy. The 12-lead electrocardiogram (ECG) showed incessant runs of supraventricular tachycardia (SVT) with a long RP interval. A careful review of the ECG helped in ascertaining the mechanism and localizing the origin of the SVT. Successful management of the tachycardia resulted in complete recovery of LV function, confirming the diagnosis as tachycardiomyopathy.A 22-year-old man presented to the out-patient department with the complaint of progressive exertional dyspnea for six months. The ECG showed global LV hypokinesia with an ejection fraction of 25%. The valve functions were normal Figure , Video 1During the electrophysiology study, there were spontaneous runs of tachycardia with the earliest atrial activation in coronary sinus (CS) 3-4 Figure . No ventAfter six months of follow-up, the patient was asymptomatic. The electrocardiogram was normal Figure , and theAF and frequent premature ventricular complexes (PVC) are the most common arrhythmias associated with tachycardiomyopathy . SVTs suTachycardiomyopathy should be suspected in all patients with LV dysfunction and an elevated mean heart rate on 24-hour monitoring, frequent PVCs, and AF [The differential diagnosis of an SVT with a long RP includes focal AT, atypical AVNRT , and orthodromic AVRT with a slow, decrementally conducting accessory pathway . While aFocal ATs start either with an ectopic beat or spontaneously. PJRT initiates during sinus rhythm after shortening of sinus cycle length, and AVNRT starts with an ectopic beat . In the Spontaneous variation in the different electrocardiographic intervals can provide valuable insights into the mechanism of SVT. Wide variations in TCL occur in AF or multifocal AT. Re-entrant tachycardia may also have subtle variation in TCL. In most re-entrant tachycardias involving the AV node, the RP interval is generally constant. However, in aAVNRT and PJRT, the RP interval may vary because of decremental conduction over the slow AV nodal pathway and accessory pathway, respectively. In PJRT, the changes in RR interval precede the changes in PP interval, while in focal AT and aAVNRT, changes in PP interval precede the changes in RR interval. In the present case, there was significant variability in TCL due to varying RP and PR intervals favoring AT as the likely diagnosis Figure .The surface ECG can help in identifying the site of origin of focal AT. Kistler et al. suggested an algorithm based on lead V1 to localize focal AT with high sensitivity and specificity; however, it is difficult to remember . A simplAll patients with tachycardiomyopathy should receive medical therapy for heart failure, including beta-blockers and renin-angiotensin inhibitors. The definitive treatment is radiofrequency ablation of the tachyarrhythmia. Drug therapy with amiodarone has moderate efficacy but significant long-term side effects. Therapy with ivabradine has shown benefit in ATs arising from atrial appendages and can be used while awaiting ablation .Tachycardiomyopathy is a reversible cause of heart failure. This case underscores the importance of identifying SVTs that can lead to tachycardiomyopathy. Careful analysis of the surface ECG helps in the diagnosis of the tachycardia. This is particularly rewarding when both onset and termination of the tachycardia can be seen on 12-lead ECG.


Occlusion of a coronary artery leads to myocardial tissue edema in the vascular bed downstream of the vessel. The extent of hyperintense edema on T2-weighted images allows the area at risk (AAR) from ischemic injury to be retrospectively determined. However, reperfusion of severely ischemic myocardium also leads to interstitial hemorrhage and this may be an important marker for irreversible microvascular damage.We assessed the feasibility of using T2* mapping to quantify regions of myocardial hemorrhage following percutaneous primary coronary intervention (PPCI) for acute myocardial infarction. We also hypothesized that myocardial hemorrhage would lead to an underestimate of the AAR on T2-weighted imaging using conventional signal threshold criteria.Fifteen patients who had recently undergone PPCI within the previous 7 days were imaged. Left ventricular function was assessed with conventional cine sequences. Myocardial edema was imaged with a T2-weighted STIR sequence. Myocardial haemorrhage was imaged with a black-blood multiecho T2* sequence using navigator respiratory-gating. Microvascular obstruction (MVO) and late enhancement were imaged at 1 minute and 15 minute delays respectively using a 3 dimensional inversion-recovery sequence.The area of myocardial edema on the T2 STIR images was measured with a boundary detection tool. This was compared to a conventional signal intensity threshold method using 2, 3 and 5 standard deviations (sd) above the mean of remote normal myocardium. A salvage index was calculated as the proportion of the AAR that did not show late enhancement. T2*-mapping of the left ventricle was performed using a threshold of 20 ms to define the presence of hemorrhage.2 = 0.75, p < 0.01) and infarct volumes  (Figure The mean area of hemorrhage was 5.0% at the level of the infarct. There was a close correlation between hemorrhage and the MVO (rOur findings demonstrate the feasibility of using T2* mapping to quantify myocardial hemorrhage following infarct reperfusion. Hemorrhage is frequently observed and is associated with large infarcts where MVO is present and is an indicator of poor myocardial salvage. Hemorrhage in the core of the infarct causes signal loss on T2-weighted imaging and boundary-detection is required to reliably assess the AAR.Studies using CMR to determine the AAR and myocardial salvage should use boundary detection methods for quantification as arbitrary signal thresholds are unreliable when hemorrhage is present. Post-reperfusion hemorrhage can be assessed with T2*-mapping and may provide an imaging marker of poor myocardial salvage.


A 24-year-old female patient without cardiac symptoms underwent preoperative echocardiography before correction of severe pectus excavatum. Echocardiography was difficult to perform because of the funnel chest, nevertheless, hypertrabeculated apical segments were diagnosed. To confirm the suspicion of non-compaction cardiomyopathy (NCCM) cardiac magnetic resonance imaging (MRI) was performed. For better visualization of non-compacted and compacted myocardium of the left ventricle (LV) a 3-dimensional (3D) whole heart sequence  covering the entire heart and adjacent thoracic structures was performed. The 3D whole heart sequence revealed a severe funnel chest Fig. a with Ha


As per the literature, patients with intraventricular conduction delay (IVCD) do not respond well to cardiac resynchronization therapy (CRT) alone. They need advanced technological approach and out of the box thinking for a good response.Ours is a case of ischemic cardiomyopathy with wide QRS-IVCD, a non-responder to CRT. While planning for replacement of the device for early replacement indicator (ERI), we decided to do His-optimized CRT/left bundle optimized CRT (HOT-CRT/LOT-CRT) for the patient.The challenges we faced with the present available hardware paved a way for insisting on the limitation of the available lumenless lead to penetrate calcified the septum and importance of the pre-procedure evaluation of intraventricular septum (IVS) for calcification by more than just echocardiography. Cardiac resynchronization therapy (CRT) has widely been used in patients of symptomatic chronic heart failure (HF) with wide QRS complex, refractory to optimal medical therapy and having left ventricular ejection fractionLVEF is < 35%. However, one third of the patients are non-responders and do not respond to this therapy. Physiological pacing, i.e., permanent His bundle pacing (HBP)/left bundle branch pacing (LBBP) is proving a promising alternative to biventricular pacing (BiVP) for some of these challenging patients. In this report, we present a case of HOT-CRTD with good outcome of physiological pacing despite challenges.A 64-year-old male patient with a known history of coronary artery disease had undergone a CRTD implant in November 2015 for IVCD with wide QRS (159 ms), QLV was 102 ms  junction was seen Fig.  a. A fluThe HB lead was attached in RV pacing port (DF1 RV lead), coronary sinus (CS) lead in LV port, and RA lead in atrial port in the new pulse generator. Previous RV pace-sense lead terminal was buried deep in the pocket. The pre-pectoral device pocket was closed in three layers; DFT (defibrillation threshold test) was not done as per protocol.The strategy of fused complex was employed whereby LV pacing timing was delayed, relative to HBP output Fig. . A narroAbout 30–50% of patients with HF who meet the criteria do not benefit by CRT . In addiThrough this case, we demonstrated that HOT-CRT is effective in correcting IVCD. It is an option particularly in patients who are CRT non-responders. Success of LBBP is dependent on IVS anatomy. Local dense scar or calcification at the septum may result in failure of LBBP. The present 3830 SelectSecureTM active pacing lead  used for LBBP has limited penetration capability. Focused hardware needs to be developed to overcome such impediment.


Conduction velocity (CV) heterogeneity and myocardial fibrosis both promote re-entry, but the relationship between fibrosis as determined by left atrial (LA) late-gadolinium enhanced cardiac magnetic resonance imaging (LGE-CMRI) and CV remains uncertain.Although average CV has been shown to correlate with regional LGE-CMRI in patients with persistent AF, we test the hypothesis that a localized relationship exists to underpin LGE-CMRI as a minimally invasive tool to map myocardial conduction properties for risk stratification and treatment guidance.3D LA electroanatomic maps during LA pacing were acquired from eight patients with persistent AF following electrical cardioversion. Local CVs were computed using triads of concurrently acquired electrograms and were co-registered to allow correlation with LA wall intensities obtained from LGE-CMRI, quantified using normalized intensity (NI) and image intensity ratio (IIR). Association was evaluated using multilevel linear regression.P < 0.001) and −0.96 m/s per unit increase in IIR (P < 0.001). The magnitude of this change decreased with larger measurement area. Reproducibility of the association was observed with NI, but not with IIR.An association between CV and LGE-CMRI intensity was observed at scales comparable to the size of a mapping electrode: −0.11 m/s per unit increase in NI (At clinically relevant spatial scales, comparable to area of a mapping catheter electrode, LGE-CMRI correlates with CV. Measurement scale is important in accurately quantifying the association of CV and LGE-CMRI intensity. Importantly, NI, but not IIR, accounts for changes in the dynamic range of CMRI and enables quantitative reproducibility of the association. Success rates of catheter ablation for persistent AF is hindered by our poor understanding of the underlying mechanisms of AF persistence. Central to improving this understanding is the relationship between local myocardial conduction properties and the underlying tissue architecture, determined clinically by estimating myocardial fibrotic burden using late-gadolinium enhanced cardiac magnetic resonance imaging (LGE-CMRI). The challenges to determining this relationship are in part due to limitations and inconsistencies in the acquisition, interpretation and the registration of high-resolution imaging and electroanatomic mapping (EAM) data to allow correlative analyses.It has previously been established that an electro-architectural relationship exists between myocardial fibrosis and CV on a regional and whole-heart level . HoweverCurrent 3D EAM systems with high-density multi-electrode contact mapping catheters can provide detailed spatio-temporal information on the functional behavior of the endocardium. Local CV can give a clear interpretation of underlying tissue health and identify the presence of non-conducting fibrotic tissue through the analysis of wave-front propagation patterns . The accLate-gadolinium enhanced cardiac magnetic resonance imaging is a well-established non-invasive technique to visualize myocardial fibrosis and has been corroborated with histomorphometric validation . FibrotiWe sought to test the hypothesis that a systematic and objective approach to the acquisition and spatial correlation of CV and LGE-CMRI data can define a reproducible electro-architectural relationship at clinically relevant scales.A diagram showing the key steps of the data collection and analysis methodology used in the study is shown in Patients with symptomatic persistent AF (based on the classification of AF by published guidelines from the AHA/ACC/HRS/ESC) presenting for their first ablation to Imperial College Healthcare NHS Trust were prospectively enrolled. The study was approved by the Local Research and Ethics Committee for Imperial College Healthcare NHS Trust and written informed consent was obtained from each patient. Patients with contraindications to undergoing LGE-CMRI were excluded from the study.Each patient underwent LGE-CMRI prior to the ablation procedure. MRI acquisition was performed using a 1.5T Philips Achieva MR system, and a 5- or 32-element phased-array cardiac coil. LGE-CMRI was performed in the axial orientation 12–20 min following the 20 ml bolus of gadobenate dimeglumine contrast agent, using an ECG triggered, free-breathing navigator-gated whole heart 3D spoiled gradient echo acquisition sequence. Resolution was at 1.5 × 1.5 × 4 mm and reconstructed to 1.25 × 1.25 × 2 mm. Complete LA coverage was obtained with 40–50 slices. Data were acquired within a window of 100–150 ms within each R-R interval depending on heart rates, with a low-high k-space ordering and spectral pre-saturation with inversion recovery (SPIR) for fat suppression. The inversion recovery delay was determined from a Look-Locker sequence, with an inversion time chosen to null myocardial signal. MRI scans were performed in patients in rate-controlled AF. To assess the robustness and reproducibility of the methodology, two patients (denoted throughout as patients G and H) underwent two pre-ablation LGE-CMRI scans, 2 weeks apart.TM, St Jude Medical, St. Paul, MN, United States) was positioned in the coronary sinus to record electrograms, pace the atrium, and serve as a temporal reference. Single trans-septal punctures were performed using a Brokenbrough needle through a fixed curve long-sheath . Unfractionated heparin was administered to achieve an activated clotting time of 300–350 s throughout the procedure.Catheter ablation was performed within 2 weeks from the LGE-CMRI scan. All anti-arrhythmic drugs were discontinued for at least 5 half-lives, and amiodarone was discontinued at least 60 days prior to the ablation procedure. All procedures were performed in the post-absorptive state under general anesthesia. Transesophageal echocardiography was performed in all patients once anesthetized to exclude LA appendage clot, and to subsequently guide transseptal puncture. A deflectable decapolar catheter  with 4 mm electrode spacing. Before each acquisition, the AFocusII catheter was held tangentially to the endocardial surface, enabling stable tissue contact. Patients presenting in AF underwent external DCCV before any mapping was conducted. Following the acquisition of the LA geometry, high-density LA activation mapping was performed. The left atrium was paced from one of more sites  at pacing rates of 250, 300, 350, and 600 ms. The pacing protocol included a drive train of 8 beats to ensure that LA capture and activation was consistent (avoiding latency and decrementation), and also to facilitate the stability of AFocusII catheter at the particular site of the left atrium that was being interrogated/mapped.An impedance-based EAM system  was used. The LA geometry and all subsequent data were acquired using a 20-pole (1 mm electrodes) double-loop catheter  was estimated both locally and regionally. Regional CV was estimated by fitting a model of an ideal circular propagating wavefront to the positions and LATs of the 20 electrodes of a given kernel. Additionally, the wavefront radius, r, and residual error, η, of the fit were calculated . High η The local CV is calculated using the principle of triangulation which uses the differences in LATs across unique groups of 3 mapping electrodes (triads) and their interelectrode distance . This apRaw absolute LA wall image intensities were extracted from the LGE-CMRI image as the maximum voxel intensity along a 3 mm inward-facing normal from the segmented epicardial surface.Left atrial wall LGE-CMRI intensities are acquired in arbitrary units and their average brightness and dynamic range varies between images, even between multiple scans of the same subject. Local gadolinium uptake was quantitatively evaluated through two intensity normalization techniques: (1) Normalized intensity (NI) is calculated from the raw intensity by subtracting the mean intensity of the LA blood pool and dividing by the standard deviation (SD) of the blood pool voxels  Image InA sub-group of two patients had two pre-ablation LGE-CMRI scans, separated by 2 weeks. Segmentation, registration and construction of the LA scar map were performed independently on each image. A single EAM dataset was used per patient for determining association. The data from each scan were included in the statistical analysis as separate datasets. If the image processing and registration methodology is reproducible, the estimated association should not be significantly different between the two scans of the same patient.Continuous variables are given as mean ± SD; categorical variables are given as percentages. A linear mixed-effects model was used to characterize the relationship between LA wall intensity, using either NI or IIR, and CV. Likelihood-ratio tests were used to compare if models, fit by maximum likelihood, were significantly different. The inclusion of CL did not significantly improve the model fit and was excluded from the final model.I, and CV, V was modeled asA multilevel model was used to characterize the relationship between LA wall intensity and CV. Multilevel models provide a mechanism to account for, and quantify, variation in model intercepts and slopes across patients and cycle lengths. The association between normalized intensity, 0 is the overall intercept, and uj and vk are random effects associated with patients and cycle lengths. β1 captures the effect due to intensity and is the primary parameter of interest in this study, representing the overall association between CV and intensity across all patients and cycle lengths. The β2j values represent per-patient random slopes; that is, the patient-specific deviation from β1. Likelihood-ratio tests were used to compare if models, fit by maximum likelihood, were significantly different. The model reported here was statistically significant (p < 0.001) compared to all other simpler models without random intercepts or slopes. The inclusion of a random slope for cycle length did not significantly improve the model fit.where βp-values with p < 0.05 were considered to indicate statistical significance. Statistical analyses were performed using R version 3.4.3 .Two-sided Due to the large number of data points collected per patient at multiple paced CL, a total of 8 patients provided sufficient data for the purposes of this study. A summary of the clinical characteristics is given in All EAM surfaces were registered to their corresponding MRI surfaces for co-localization of image intensity with CV. Average target registration errors were 3.08 mm (range 1.94–5.71 mm).A total of 267 kernels were acquired across all patients, comprising a total of 5340 mapping points. In total 171 kernels were rejected due to non-planarity of the underlying wavefront (η < 5 s/mm). A total of 96 complete or partial kernels  remained. An average of 435 triads were formed per kernel (range 1–1140 triads/kernel).An overview of the data used in this study is shown in An example of the distribution of gadolinium enhancements using NI  is shown in 2 to 590 mm2. The change in CV per unit increase in LGE-CMRI intensity, denoted β1, was measured across all patients and CL. The effect of measurement area on this slope was studied by binning triads by their area and fitting the model to those triads within each bin separately. Bins were chosen as 10 mm2 wide non-overlapping intervals in the range 0–160 mm2. Beyond this range there were insufficient data to generate reliable statistical models. 2 were considered for the remainder of the study.Triads were only formed within individual kernels from those electrodes in good contact with the myocardium. Triad areas ranged from 0.12 mmp < 0.001). The CV at 0 S.D. (model intercept) was 1.00 m/s, which is within the expected physiological range of healthy myocardium . Conduction velocity correlated with LGE-CMRI intensity . Only one CL (350 ms) had an intercept significantly different from the overall intercept. Variations in the intercepts with CL were two orders of magnitude smaller than the overall intercept, suggesting there is negligible change in the relationship with respect to CL.For Patients G and H, who underwent two LGE-CMRI scans, the images were independently segmented, registered with the clinical data and fused to examine reproducibility. These are shown as G1, G2, H1, and H2 in p < 0.001). The CV was estimated as 1.00 m/s at an IIR value of 1.0, which corresponds to an NI value of 0 S.D. Per-patient slopes and intercepts for the association of CV with IIR are shown in Left atrial wall intensity was assessed using NI and IIR. The statistical model was modified to also examine the relationship between IIR with CV. This identified a change in CV of −0.942 m/s per unit increase in IIR , the average maximal edge length of each triad was 15.4 mm (range 5.9–20.0 mm). For comparison, the typical contact area of the ablation electrode is approximately 10 mm2 (3.5 mm diameter). Intuitively, averaging over larger areas diffuses the effect of small-scale variations in the quantities of interest and potentially masks the true localized association between them. In the atrium this is crucial, due to the patchy and non-uniform nature of atrial fibrosis (1: −0.942 m/s/IIR), at smaller spatial scales of areas <80 mm2, and that of Fukumoto et al. (β1: −0.34 m/s/IIR). To explain this, The area subtended by the triads used in the analysis had a clear influence on the resulting beta estimate. In this study, the association is determined using triads of area <80 mmfibrosis . As showfibrosis . FukumotWhile both scans for each patient in the reproducibility sub-study were compared with the same EAM data, our experience suggests that the segmentation and co-registration steps are most prone to the introduction of errors. Importantly, the relationship between CV and NI within each pair of datasets were statistically indistinguishable, confirming the accuracy and reproducibility of our approach.One significant contribution of our study is a comparison between the IIR and NI metrics for the qualitative assessment of independently acquired MR images.By its definition, IIR accounts for underlying shifts in the intensity spectrum, while NI includes the standard deviation of the blood pool to account for inter- and intra-patient differences and accordingly for differences in the dynamic range of the images. Consequently, NI led to a more robust statistical model for elucidating the relationship between CV and intensity, compared with IIR, as well as improved reproducibility of the patient-specific association. In particular, the 95% confidence intervals on the intercept and slope estimates for IIR, shown in No statistically significant effects due to CL were observed, indicating no identifiable CV restitution.In order to obtain high fidelity electrograms, electroanatomical data were limited to the posterior LA, which was anatomically consistent, conducive to placement of the AFocusII mapping catheter tangential to the endocardial surface, and contained a predilection of fibrosis. Sampling from the posterior wall may have potentially introduced sampling bias. Future studies should incorporate contact sensing catheters to increase robustness of the data collection protocol.This study investigated a persistent AF cohort which has been shown to have more extensive structural and electrical remodeling compared to paroxysmal AF patients. Future studies should include a more heterogeneous group of patients.The image MR images used in this study were manually segmented to delineate the epicardial wall of the left atrium. As such, errors may have been introduced during the segmentation process.Image intensity ratio is defined as the ratio of the wall intensity of the sector to the blood pool mean . However1. Importantly, NI, but not IIR, accounts for changes in the dynamic range of LGE-CMRI and improves the quantitative reproducibility of the relationship. Evaluation of the LA substrate with the use of normalized intensity from LGE-CMRI can be potentially used as a minimally invasive tool to predict atrial myocardial conduction properties.Higher LA intensities correspond to lower local myocardial conduction velocities. The scale of measurement of CV and LA wall intensity is crucial in accurately quantifying this relationship, which is found to be of a higher magnitude than previously reportedThe raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Local Research and Ethics Committee for Imperial College Healthcare NHS Trust. The patients/participants provided their written informed consent to participate in this study.RA, NQ, and CC conceived and planned the experiments. RA developed and implemented the algorithms. NQ obtained the clinical data and segmented the MRIs. SL and CC developed the statistical model and performed the statistical analysis. CR and SK contributed to the interpretation of the results. PL, JT, and NP helped supervise the project. All authors provided critical feedback and helped shape the research, analysis and manuscript.SK was employed by the company Abbott United States. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.