The extracellular volume fraction (ECV) derived from cardiac magnetic resonance imaging (MRI) is extensively used to evaluate myocardial fibrosis. However, due to the limited histological verification in healthy individuals, it remains unclear whether the size of cardiomyocytes may play a potential role in the physiological changes of ECV. The aim of this study was to examine the association between cardiomyocyte size and myocardial ECV by using a healthy porcine model.Sixteen domestic healthy pigs were anesthetized and underwent cardiac MRI with mechanical controlled breathing. Intravenous contrast medium was introduced at a dose of 0.2–0.25 mmol/kg. The interventricular septum ECV was calculated using an established MRI procedure, which was based on the pre- and post-contrast T1 values of the heart and individual blood hematocrit. The cardiomyocyte breadth (CmyB) in cross section was measured by hematoxylin and eosin staining to reflect the cardiomyocyte size.r = −0.729, p = 0.003).Data were successfully acquired from 14 pigs. The CmyB was obtained from the myocardial tissues corresponding to the region of interest on cardiac MRI. The mean ± SD of the ECV was 0.253 ± 0.043, and the mean ± SD of the CmyB was 10.02 ± 0.84 μm. The ECV exhibited a negative correlation with the CmyB (The myocardial ECV detected by cardiac MRI is negatively correlated with the CmyB in healthy pigs, demonstrating that the size of cardiomyocytes is potentially associated with the ECV under physiological conditions. A six-channel surface array coil and a six-channel spine coil were used for signal acquisition. The short axis plane at the mid-papillary muscle level was selected as the scanning dimension, and a modified Look-Locker inversion-recovery (MOLLI) sequence was used for T1 mapping. The T1 map before the enhancement was obtained with a MOLLI4(7)3 acquisition sequence, and the T1 maps at 1 to 60 min after the enhancement were obtained with repeated MOLLI4(3)3 acquisition sequences as we previously reported . The intThe enhanced scanning procedure was performed with gadolinium  at the dose of 0.2–0.25 mmol/kg, which was rapidly injected through the ear vein (approximately 0.5 mL/s), followed by flushing the vein with 5 mL saline. The region of interest (ROI) was carefully selected from the interventricular septum, avoiding the cardiac-blood border zone, for calculation of the ECV. The ECV was calculated using an established equation: ECV = λ × (1 – hematocrit), where λ was separately calculated in each animal using a multi-point regression method and was equal to the slope of the linear regression for the individual myocardial R1 value plotted against the left ventricular blood R1 value in the equilibrium state, as described in our previous study , and theThe animals were euthanized after the cardiac MRI procedure by an intravenous injection of a high concentration of potassium chloride. The heart was completely separated, and each heart chamber was rinsed with saline. The left and right ventricles were filled with 3% agarose gel, and the heart was embedded. The structure and volume of the left and right ventricles were retained. Sectioning was performed using a specialized slicer with a thickness of 6 mm and carefully matching the corresponding scan layer of the cardiac MRI. In the resulting slice, the obtained interventricular septum tissue was divided into two sections consisting of the anteroseptal region and the inferoseptal region. After removing the junction of the left and right ventricles, the specimen was fixed in formalin solution for 48 h. The following biopsy work was performed by a pathological technician  who was blind to the cardiac MRI study. The tissue was selected, and the orientation of the tissue block was labeled, followed by paraffin sectioning with the slice thickness of 4 μm. The slicing dimension was perpendicular to the annular fibers of the midmyocardium.Conventional hematoxylin and eosin (H&E) staining were performed. A cross-section of the midmyocardium fibers was viewed under a 200 × optical microscope (Olympus), and the boundary of the inner and outer layers was identified. The midmyocardium fibers were divided into four equal areas in the direction of the endocardium to the epicardium. Under 400 × magnification, a random field was selected from each area , and the images of the fields of view were captured and saved. Thus, images of the cross section of the midmyocardium fibers from eight interventricular septa of each animal were obtained at 400 × magnification, and more than one thousand cells were measured in each animal. Off-line measurements and analyses were performed using dedicated software (Image-Pro Plus 6.0) by 2 blinded readers . The cross-section of each cardiomyocyte with an intact and approximately oval, blue-stained nucleus in each center was included in the analysis. The cross-sections were approximately oval-shaped, and the shorter diameter of this oval was recorded as the CmyB .A total of 28 pathological slices was acquired from 14 pigs with two slices per animal. Then, a subset of 12 slices was randomly selected to measure the interobserver and intraobserver variability. To derive the interobserver variability, two blinded investigators were asked to choose the fields of view and perform these measurements by themselves. To assess the intraobserver variability, one blinded investigator measured the same slices again on a separate day and performed these measurements twice.p-value less than 0.05 was considered a statistically significant difference.Normal distributions of variables were evaluated before analysis using the Shapiro–Wilk test. The values of ECV and CmyB were processed as continuous variable of normal distribution according to previous studies and were reported as means ± standard deviation (SD) , 4–9, 18One of the 16 pigs died of suffocation during the cardiac MRI procedure due to a failure of endotracheal intubation  with a mortality rate of 6.25%, and another animal experienced enhanced scan failure due to severe extravasation of the contrast agent caused by poor care for the ear vein access . The data of 14 pigs were included in the final analysis, and detailed gender, age, heart rate, systolic blood pressure, hematocrit, body weight, ECV and CmyB values were acquired . DynamicWe acquired the short-axis T1 maps at the mid-papillary muscle level pre- and post-contrast of the animals. Although artifacts occasionally appeared on the free wall of the left ventricle, there was no artifact in the ventricular septum . Thus, TThe relationship between the myocardial R1 value and the blood R1 value pre-contrast (0 min) and post-contrast (5–60 min) in each pig was illustrated , and theMyocardial sections with a thickness of 6 mm carefully matches the corresponding scan layer on cardiac MRI . The H&Er = −0.729, p = 0.003)  .via large animal experiments of pigs. To our knowledge, this is the first study that uses a healthy porcine model to study the relationship between the ECV and the CmyB by using in vivo cardiac MRI and ex vivo myocardial pathology.Extracellular volume fraction has been widely used in the field of cardiovascular imaging, showing great potential due to its unique properties in the non-invasive evaluation of subtle abnormalities such as diffuse fibrosis and post-infarct remodeling of remote myocardium in cardiovascular diseases –23. HoweCardiac ECV is a quantitative value that could reflect various myocardial tissue characterization, especially myocardial fibrosis –34. HistPrevious studies by our research team have shown that the variations of ECV detected by cardiac MRI in healthy individuals follow certain rules, which indicates that the ECV and cardiomyocytes are intrinsically linked . In the So far, research on the size of cardiomyocytes has been largely limited because it is difficult to acquire biopsy in humans, especially in healthy people. Under physiological conditions, the size of cardiomyocytes may be related to several factors such as age, height, weight, hormone levels and different volumes of exercise, some of which have already been confirmed by cardiac MRI or myocardial autopsy –44. In aIn the current study, we used a healthy porcine model to explore the relationship between the ECV and the CmyB, and a significant negative correlation was observed between the ECV detected by cardiac MRI and the CmyB detected by pathological analysis. These results highlight the importance of CmyB to be considered as a direct influencing factor of ECV, and emphasize the necessity to explain ECV in terms of both the volume of extracellular space and the volume of cardiomyocytes. Moreover, our research may help explain why ECV is affected by the above-mentioned physiological factors  in the absence of diseases that can cause changes in the extracellular volume . It is probably that compared with the volume of extracellular space, the volume of cardiomyocytes may have a greater impact on ECV under physiological conditions. Besides, it is potentially that CmyB might also be one of the influencing factors of ECV in diseased individuals, especially patients with altered sizes of cardiomyocytes, such as hypertrophic cardiomyopathy and Anderson-Fabry disease , 50, whiTo date, no simple and practical method has been developed to measure the size of cardiomyocyte in three dimensions in a slice because the intercalated disk structure of a cardiomyocyte may not be fully displayed in one slice, and it is difficult to distinguish the boundaries of two adjacent cardiomyocytes. In addition, because cardiomyocytes show some degree of localized distortion, it is not practical to obtain a standard section of the major axis or minor axis. If the major axis of the cardiomyocyte is not precisely vertical in the section, the resulting short-axis section will be oblong. When the tilt angle is increased, the longer diameter of the oblong axis will be further increased, while the shorter diameter will remain unchanged. Therefore, measurement of the shorter diameter can be more stable and accurate in describing the CmyB, as mentioned in a previous study . Thus, hSome limitations were present in this study. Firstly, the study had a small sample size. Due to the limited number of samples, further stratified analyses were not implemented; for example, it has not been determined whether gender influences the results. Despite that, we have already uncovered a negative correlation between the ECV and the CmyB, and confirmed the importance of CmyB in ECV interpretation. Further experiments depending on a larger sample size will improve our results. Secondly, an artifact occasionally occurred in the free wall that might affect the calculation of the ECV in this region. Thus, the analysis of the ECV and the myocardial histology was restricted to the interventricular septum to avoid artifacts. Finally, formalin fixation can cause cell shrinkage  and hypein vivo cardiac MRI. Although with limited sample size, we hypothesize that a change in the volume of cardiomyocytes may be associated with a change in the ECV, and the difference in the size of cardiomyocytes may exert a key role in the physiological alterations of the ECV. These observations are novel and potentially important for clinical application, especially in understanding the inter-subject variations of the ECV in healthy myocardium under physiological state, and might potentially explain early pathological changes of cardiovascular diseases observed via ECV through cardiac MRI. Moreover, the current results strongly suggest that in addition to the extracellular space, we should take CmyB into consideration when interpreting the ECV detected by cardiac MRI in healthy individuals, and potentially in diseased individuals, especially patients with altered sizes of cardiomyocytes, such as hypertrophic cardiomyopathy.Our study demonstrated a significant negative correlation between the ECV and the CmyB in a healthy porcine model, suggesting that an increase in the CmyB under physiological conditions can lead to a decrease in the ECV as detected by The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The animal study was reviewed and approved by Institutional Animal Use and Care Committee of the Southeast University.S-JZ, DC, and SJ are the guarantors of integrity of the entire study and participated in the design and coordination of the study. S-JZ, DC, and J-YJ conceived the study, and acquired and analyzed the cardiac MR data. J-YJ, Y-LW, and LW performed the pathological analyses. DC, Y-LW, LW, Y-CW, and ZW performed the statistical analyses. S-JZ and DC drafted the manuscript. All authors have read and approved the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Even when added age and hypertension to the model, current HbA1c level remained independent predictor of left ventricular GLS (p = 0.002), GCS (p < 0.001), mitral e’ (p = 0.018), tricuspid e’ (p = 0.018) and left (p = 0.039) and right atrial conduit strain (p = 0.047) in multiple linear regression models. Correlations between disease duration and the echocardiographic variables lost their significance in multiple models. In patients with a combination of HbA1c ≤ 7.4% and no hypertension, echocardiographic findings did not differ from those in healthy volunteers. Patients with HbA1c > 7.4% and no hypertension and especially patients with coexisting hypertension and HbA1c > 7.4%, exhibited significantly impaired myocardial mechanics. Quality of glycemic control has a significant impact on myocardial mechanics in T1DM patients. Regarding disease duration this relationship was not proved.The potential associations between disease duration, glycemic control, and the echocardiographic markers of the myocardial mechanics were investigated in asymptomatic T1DM patients. Seventy T1DM patients  and 30 healthy volunteers were investigated. Besides the conventional and tissue Doppler measurements, left ventricular global longitudinal (GLS) and circumferential (GCS) strain as well as left and right atrial strain parameters were measured with 2D speckle tracking technique. Median HbA Besides, heart failure develops 10–15 years earlier in T1DM patients than in the general population3. Although in young asymptomatic T1DM patients the standard echocardiographic parameters reflect normal cardiac size and function4, tissue Doppler imaging (TDI) and speckle tracking echocardiography seem to be useful techniques for assessing subclinical myocardial involvement in this population. Left ventricular (LV) systolic dysfunction was proved by speckle tracking-derived global longitudinal strain (GLS) data, both in T1DM children and adults12, whereas TDI measurements suggested impaired LV diastolic function15. Nevertheless, conflicting results were also reported18. Less is known about right ventricular (RV) function19, or atrial performance20 in this disease.Type 1 diabetes mellitus (T1DM) is one of the most common chronic disorders affecting young adults. It is associated with serious microvascular and macrovascular complications resulting in at least tenfold increase in cardiovascular diseases as compared with the age matched healthy population3. Data about their effect on myocardial mechanics, however, are scarce and controversial.Duration of diabetes and quality of the glycemic control have been reported as critical factors contributing toward development of cardiovascular complicationsThus, our work aimed to provide a comprehensive analysis of the myocardial size and function using standard and novel echocardiographic techniques and to investigate the potential associations between disease duration, glycemic control, and the echocardiographic markers of the myocardial mechanics in asymptomatic T1DM patients.1c%) and other laboratory markers were collected within a 30-day period before inclusion. An age- and gender-matched group of 30 healthy volunteers without any signs or symptoms of cardiac disease was used as control. The study complied with the Declaration of Helsinki. The Regional Research Ethics Committee, Clinical Centre, University of Pécs approved the study. All subjects had given written informed consent before inclusion in the study.Seventy-five asymptomatic patients without known cardiovascular disease, diagnosed with T1DM in the tertiary center of 2nd Department of Internal Medicine, University of Pécs were recruited for our prospective study. Detailed medical history was obtained. Patients with impaired LV systolic function (LV ejection fraction (EF) < 55%), significant left-sided valvular disease, atrial fibrillation, known coronary artery disease (CAD), substantial peripheral artery disease or with diabetic nephropathy or retinopathy were excluded from the study. Treadmill exercise test was performed to exclude the patients suspicious for CAD. Blood samples for serum glycated hemoglobin , elevated (≥ 0.43) relative wall thickness and enlarged LV chamber size  were considered as signs of the hypertensive heart disease22.Echocardiography was performed using Philips Epiq 7 ultrasound system  by a single investigator. LV EF was measured by Simpson's method. End-diastolic thickness of the septum and the posterior wall and the end-diastolic diameter of the LV were measured from parasternal long-axis view by M-mode. LV mass was calculated according to the Devereux formula and corrected for body surface area (LVM index)23. Basal dimension of the RV was obtained at end-diastole in RV-focused apical four-chamber view and corrected for body surface area. As parameters of the RV systolic function, tricuspid annular plane systolic excursion (TAPSE) and RV fractional area change (RVFAC) were measured. Maximal and minimal diameters of the inferior vena cava (IVC) were measured in the subxiphoid view, and collapsibility index (the percent decrease in the diameter of IVC with inspiration) was calculated. RV wall thickness was measured at end-diastole in a zoomed subxiphoid view. Systolic pulmonary artery pressure was estimated as a sum of the pressure difference across the tricuspid valve  and an estimate of mean right atrial (RA) pressure (5 to 15 mmHg) using the diameter and collapsibility index of the IVC24. Doppler measurements were obtained from 3 consecutive beats during end-expiratory apnea.In addition to the spectral Doppler parameters of the transmitral and transtricuspid flow  Fig. 23.LV diastolic function and filling pressure were classified according to the current recommendationFor strain analysis, three consecutive heart cycles were recorded digitally, and processed off-line, using a dedicated software . The analysis was performed by a single investigator, blinded to the clinical and conventional echocardiographic data. In segments with poor tracking, endocardial borders were manually readjusted until better tracking was achieved. To estimate LV GLS, apical four-, three- and two-chamber movies were obtained using 2D echocardiography. Care was taken to obtain true apical images using standard anatomic landmarks in each view. Foreshortening was avoided. The frame rate was set between 50 and 55 frames per second. Regional peak systolic longitudinal strain was determined in all 17 segments from the three apical views  were obtained using 2D echocardiography Fig. D,E. The 26.Using the atrial borders created for speckle tracking analysis, the same software generated left and right atrial volume curves. Atrial volumes were measured at different time points of the cardiac cycle: maximal volume (Vmax) at the end of T wave on electrocardiogram, just before the opening of the mitral or tricuspid valve; minimal volume (Vmin) at QRS complex, at the closure of the mitral or tricuspid valve; and preceding atrial contraction, at the beginning of P wave (Vp). LA volumes obtained in apical four- and two-chamber views were averaged. All volume values were corrected for body surface area U test was used to compare means of two variables not normally distributed.Categorical data were expressed as n (%). The frequencies of categorical variables were compared using chi-square test or Fisher's exact test. The normality of distribution of continuous variables was tested by Shapiro–Wilk test. Continuous variables with normal distribution were presented as mean ± standard deviation; non-normal variables were reported as median (interquartile range). Means of two continuous normally distributed variables were compared by independent samples Student’s t test. Mann–Whitney 1c or disease duration were determined using bivariate Pearson correlation. In a second step, multiple linear regression analysis (enter method) was used. Age-related changes in the echocardiographic parameters are well known, thus age was added to the multiple models. ACE inhibitors/ARBs are often used as treatment or prevention of diabetic nephropathy, regardless of the presence of systemic hypertension. Thus, medical therapy was not useful in identifying patients with hypertension. To eliminate the influence of the hypertension on the echocardiographic variables, signs of hypertensive heart disease were recoded (1 = sign(s) are present; 0 = sign(s) are not present) and used as additional variable in the multiple models. Partial regression plots were used to visualize the correlations between HbA1c and echocardiographic variables . Partial correlation coefficients were reported on the plots.Echocardiographic variables that correlate with current HbA1c level and the presence/absence of the hypertensive heart disease. Four groups were created according to the number of cardiovascular risk factors: normal volunteers (NORM); patients below the median HbA1c and without hypertensive heart disease (T1DM-LOW); patients above the median HbA1c but without hypertensive heart disease (T1DM-MED); patients above the median HbA1c and with hypertensive heart disease (T1DM-HIGH). Patients with hypertensive heart disease but below the median HbA1c were excluded from sub-grouping. Comparisons of normally distributed data among multiple groups were performed using one-way ANOVA with LSD post hoc test. Kruskal–Wallis test with Dunn's multiple comparison test was used to compare means of multiple groups of variables not normally distributed.Patients were subgrouped according to the median HbAA p-value of < 0.05 was considered significant. Data were analyzed using IBM SPSS 27 statistical software.Of a total of 75 patients, 70  were eligible for the study. Four subjects were excluded due to inadequate acoustic windows. In one patient, ST changes observed during the exercise test suggested significant CAD, and this diagnosis was later confirmed by coronary angiography. Detailed clinical data of the T1DM patients are reported in Table Patients and controls were matched for age, gender, BSA and BMI. LV EF was significantly higher in T1DM patients compared with healthy controls. This difference, however, was clinically not remarkable. More negative GCS values suggested enhanced LV circumferential function in T1DM population. On the contrary, LV GLS values were similar in both groups. Averaged mitral annular S and e′ values were significantly lower, whereas LV E/e′ ratio was significantly higher in T1DM patients, but typically within the normal range. Mitral e′ values suggested impaired relaxation in 11 patients (15.7%). Six (8.6%) of these exhibited normal LV filling pressure, whereas in 5 (7.1%) patients indeterminate LV filling pressure was found.RWT was significantly higher in T1DM patients. LV hypertrophy, abnormal RWT and elevated EDD/height were found in 6, 23 and 1 cases, respectively .In the right heart, tricuspid S was significantly reduced in the T1DM population. Real RV systolic dysfunction, however, was rare: RVFAC < 35%, TAPSE < 16 mm and tricuspid S < 10 cm/s were found in 1 (1.4%), 0 (0%) and 3 (4.3%) patients, respectively.Regarding atrial size or function, no differences were found between the groups. Detailed echocardiographic data of the 70 patients compared to healthy controls are reported in Table 1c and disease duration showed significant correlations with various echocardiographic parameters .Both HbArs Table . Even whls Table  whereas ses Fig. .Table 2S1c level was 7.4 (1.8)% in our T1DM population. Twenty-four patients had HbA1c ≤ 7.4% and no signs of hypertensive heart disease (T1DM-LOW group). Nineteen and sixteen patients exhibited HbA1c > 7.4%, without (T1DM-MED group) or with (T1DM-HIGH group) signs of hypertensive heart disease, respectively. T1DM-HIGH-patients were significantly older than NORM and T1DM-LOW-patients and had significantly higher BMI compared with T1DM-MED and NORM groups. In T1DM-LOW-patients significantly lower LVM index was found compared with NORM. Otherwise, echocardiographic findings in T1DM-LOW-patients did not differ significantly from those in NORM. In T1DM-HIGH-patients LV GLS, mitral S, mitral E/A, mitral e′ and LA conduit strain were significantly reduced, whereas E/e′ values were significantly elevated compared with NORM, reflecting the impairment of LV longitudinal systolic and LV diastolic function. In contrast, LV EF, mitral A and  GCS were significantly higher in T1DM-HIGH group compared with NORM, suggesting the compensatory behavior of these parameters. Regarding the right heart, tricuspid e′ and RA conduit strain values were significantly reduced, whereas tricuspid E/e′ was significantly elevated in the T1DM-HIGH subgroup. In general, signs of the myocardial involvement were pronounced in T1DM-MED and T1DM-HIGH subgroups compared with T1DM-LOW-patients. The differences between T1DM subgroups, however, were not always significant, especially not between T1DM-MED and T1DM-HIGH subgroups 16. Besides, in the studies of Hensel et al.17 and Weber et al.18, relatively good glycemic control was associated with preserved LV GLS. Similarly to the latter findings, mean LV GLS value was preserved in our T1DM population, compared with healthy controls. In patients with HbA1c above the median, however, significantly impaired LV GLS values were found. Bakhoum et al. found that HbA1c, but not the disease duration, was independent predictor of GLS5. Similar findings were reported by Labombarda et al.8. In our study, HbA1c levels showed significant relation with LV GLS values, even in age and hypertension adjusted multiple regression model. By reviewing the results of the previous studies this tendency is confirmed even at global level: in T1DM populations with relatively good glycemic control the mean LV GLS is preserved18, whereas worse glycemic control is associated with impaired GLS12 . These data may suggest that LV GLS is less sensitive to the mild changes in LV longitudinal systolic function than the other two parameters.34. Prevalence of diastolic dysfunction was reported as 8% by Palmieri et al.4, whereas 27.4% of the patients had diastolic damage in the work of Raev et al.35. Discrepancies between these results may be explained not only by the variability of the populations but by the various echocardiographic methods applied in these studies. Regarding the modern, tissue Doppler-derived parameters, the result are similarly contradictory. Bakhum et al. reported, that mitral annular e′ values were preserved, but E/e′ values were higher in T1DM patients than those in healthy subjects5. In contrast, Weber et al. detected mildly reduced mitral e′ values. Mitral E/e′, however, was not elevated in their study18. Finally, in the studies of Jędrzejewska et al. and Gul et al., mitral annular e′ values were significantly lower, whereas LV E/e′ ratio was significantly higher in T1DM patients compared with healthy subjects, but typically within the normal range13. Our findings are in line with the latter studies: in our study-population, mitral annular e′ values were reduced, whereas mitral E/e′ values were elevated, but mainly within the normal range. LV diastolic dysfunction was found in 15.7% of our patients.Literature data about LV diastolic function are inconsistent in T1DM patients. Di Cori et al. did not detect any diastolic functional abnormalities in young asymptomatic patients with TDM11c nor disease duration showed significant correlation with the parameters of LV diastolic function in the study of Bakhoum et al.5. In contrast, mitral annular e′ correlated significantly both with HbA1c values and disease duration, as reported by Weber et al.18. Although tissue Doppler parameters were not used in their study, Grandi et al. reported that diastolic dysfunction could be prevented and reversed by tight glycemic control in T1DM patients36. Our results are partially in agreement with the latter studies: both mitral annular e′ and E/e′ showed significant correlation both with HbA1c and disease duration in our population. In multiple regression model, however, only the association between HbA1c and mitral e′ remained significant.Neither HbA15. In contrast, in the study of Ahmed et al., a young T1DM group showed statistically significant decrease in tricuspid S and in RV longitudinal strain. Tricuspid E/e’ was significantly elevated, but tricuspid e′ was preserved in their study19. Although TDI-derived parameters of their RV function were preserved, Jȩdrzejewska et al. also reported significantly impaired RV longitudinal strain in T1DM patients7. At population level, tricuspid S was significantly reduced in our study, but no significant reduction of tricuspid e′ was proved. On the other hand, in the subgroup of T1DM patients with less well controlled diabetes and hypertensive heart disease, tricuspid e′ was significantly reduced, whereas tricuspid E/e′ was significantly elevated, suggesting RV diastolic dysfunction. Correlations between RV function and HbA1c or disease duration have not been reported in the literature. In our population tricuspid e′ showed significant association with HbA1c level, even in multiple regression model.Similarly to the left heart, Karamitsos et al. revealed preserved RV longitudinal systolic function in T1DM, whereas tricuspid e′ was reduced in their patients, suggesting impaired RV relaxation37. This finding, however, was not confirmed in our study. Acar et al. investigated LA function based on volumetric measurements, in T1DM children and adolescents. LA passive emptying fraction, reflecting LA conduit function, was decreased, whereas LA active emptying fraction, reflecting contractile function, was increased in their patients compared with healthy controls14. Similarly, Ifuku et al. reported reduced LA reservoir and conduit strain in adolescents and young adults with T1DM20. Regarding RA strain, data are available only in T2DM patients: Tadic et al. reported reduced reservoir and conduit but enhanced contractile strain both in LA and RA38. In contrast, at population level, both LA and RA phasic functions were found to be preserved in our T1DM patients compared with healthy controls. Nevertheless, in the subgroup of patients with less well controlled diabetes and hypertensive heart disease, both LA and RA conduit strain were significantly reduced compared with healthy subjects, whereas compensatory increase of LA and RA contractile strain were found when compared with those having well controlled diabetes. This compensatory behavior of LA contractile function—parallel with the decline of LV diastolic function—has already been reported in other conditions40. LA conduit strain showed significant correlation with disease duration, as reported by Ifuku et al.20. Besides, in T2DM, LA conduit and reservoir strain, as well as RA conduit and contractile strain were independently associated with HbA1c levels38. In our T1DM population, even in multiple regression model, HbA1c levels showed significant associations with LA and RA conduit strain. Significant correlations were also proved between LA reservoir and conduit strain and disease duration. In multiple regression models, however, the latter associations were lost.Nemes et al. reported enlarged LA volumes in T1DM patients1c level, our asymptomatic T1DM population exhibited a relatively well controlled diabetes compared with the populations reported in the previous studies. This may, at least partially, explain the differences.Regarding myocardial mechanics, our results are only partially in agreement with the previous findings. Nevertheless, due to the lack of uniformity in patient-selection  and in the use of the echocardiographic techniques, the results of the studies are not easy to compare. Based on their mean HbA1c and the risk of heart failure in their study3.As new finding, our comprehensive analysis suggests that in asymptomatic T1DM patients, glycemic control has significant impact on the mechanics of all cardiac chambers, even after careful correction for the main confounding factors. This early myocardial damage forms the basis of the future heart failure in patients with poor glycemic control. Our results are in line with the large observational study performed in a cohort of 20,985 T1DM patients by Lind et al. A strong positive association was found between HbANumerous limitations of our study need to be acknowledged. First, our study population was limited in size due to the challenging selection of patients without cardiovascular comorbidities. Neither daily physical activity, nor statin or fibrate use of the patients are reported. Treadmill exercise test was performed to exclude patients suspicious for CAD. Due to ethical reasons, use of coronary angiography was avoided in asymptomatic subjects.Patients with well-controlled hypertension were not excluded from the study, but we intended to eliminate the confounding effect of hypertension in our analysis.For obtaining atrial strain values, we used a software that was developed for LV strain analysis because dedicated software was not available. RV strain may better reflect the subclinical impairment of the RV systolic function than our traditional and tissue Doppler parameters. Nevertheless, in the lack of appropriate analytical software, RV strain analysis was not performed in our study.Alpha level was not adjusted when multiple comparisons were made. This may increase the chance of type 1 error .Our data suggest that quality of the glycemic control has a significant impact on the subclinical myocardial involvement in T1DM patients. Regarding disease duration, we could not prove this relationship. Thus, tight glycemic control must be a high-priority therapeutic aim for diabetic patients to minimize the risk of myocardial damage and consequential heart failure.


Permanent cardiac pacemakers have been standard therapy for bradycardia and conduction disturbances for more than six decades. Since the first pacemaker implantation in 1958, on-demand dual chamber pacing and algorithms to optimise atrioventricular synchrony and promote intrinsic conduction have been developed, cardiac resynchronisation has been introduced, and completely leadless systems have been implanted in the right ventricle—most often in the right ventricular apex. However, chronic right ventricular apical pacing results in cardiac dyssynchrony, which may lead to pacing-induced heart failure, particularly in patients with diminished left ventricular function . Netherlands Heart Journal, which is dedicated to electrophysiology in Dutch clinical practice, Heckman and colleagues describe their investigation of the feasibility and the learning curve of LBB area (LBBA) pacing [This has led to the introduction of conduction system pacing: pacing from the His bundle or left bundle branch (LBB) to maintain the normal ventricular activation sequence and prevent pacing-induced heart failure. In this issue of the) pacing . LBBA ca) pacing .Subsequently, Rademakers and colleagues report on their first experience with LBB pacing . They deOne of the major disadvantages of (transvenous) pacing, including LBB pacing, is the potential need for extraction of one or more pacemaker leads during follow-up for various reasons. Bracke et al. therefore report probably the largest series of lead extractions in the Netherlands . BetweenThis Electrophysiology issue is complemented with two papers on atrial fibrillation ablation. Van Deutekom and colleagues report their series of cryoballoon ablation for atrial fibrillation, with emphasis on heart rate increase and inappropriate sinus tachycardia . From thLiebregts et al. describe their first experience with the AcQMap system to ablate complex atrial arrhythmias using multi-electrode non-contact mapping in 21 patients . At 12 m Netherlands Heart Journal provide us with insight and understanding of new techniques, but more importantly, they underscore the continuous innovation in our field.Together, these contributions to this special issue of the


Menor redução da pressão arterial (PA) noturna, conhecida como hipertensão não-dipper, é um forte preditor de morbimortalidade cardiovascular. Este estudo visou investigar a relação entre a hipertensão não-dipper e a gravidade e complexidade da doença arterial coronariana usando o escore SYNTAX em pacientes hospitalizados com síndrome coronariana aguda. Foram selecionados 306 pacientes consecutivos com síndrome coronariana aguda. Pacientes clinicamente estáveis internados na unidade de terapia intensiva intermediária pelo menos 24 horas após a angiografia e/ou revascularização bem sucedida. Após os critérios de exclusão, foram incluídos 141 pacientes . A hipertensão não-dipper foi definida como uma queda de 0% a 10% na PA sistólica média durante a noite em comparação com o dia, medida em intervalos de 1 hora, usando o mesmo dispositivo automático de medição de PA em monitores de beira de leito . O escore SYNTAX foi calculado com uma calculadora online. Os preditores independentes do escore SYNTAX foram avaliados por meio de análise de regressão logística multivariada. P < 0,05 foi considerado estatisticamente significativo. Os pacientes com hipertensão não-dipper apresentaram escore SYNTAX maior do que os pacientes com hipertensão dipper . Em um modelo de regressão logística multivariável, o status de hipertensão não dipper , sexo  e colesterol de lipoproteína de baixa densidade  emergiram como preditores independentes de alto escore SYNTAX. Os resultados do nosso estudo fornecem um possível mecanismo adicional ligando o perfil anormal da PA circadiana à gravidade e à complexidade da doença arterial coronariana em pacientes com síndrome coronariana aguda. Por outro lado, alternativamente, a monitorização clínica da pressão arterial (MCPA) em pacientes hospitalizados e a monitorização domiciliar da pressão arterial (MDPA) em pacientes ambulatoriais são realizadas com medidas manuais ou medidas automáticas infrequentes da PA. A MCPA e a MRPA mostraram anteriormente terem medidas de PA diurna e noturna semelhantes à MAPA em pacientes hospitalizados e ambulatoriais e serem consistentes com a MAPA na verificação de hipertensão não-dipper.10A pressão arterial (PA) fisiológica apresenta um padrão circadiano com queda de 10% a 20% durante o sono em relação à PA diurna. Essa diminuição durante o sono é definida como dipping extremo quando ≥ 20%, dipping normal quando encontra-se entre 10% e 20%, não-dipping quando < 10% e dipping reverso se houver algum aumento .13 No entanto, o significado clínico da variação circadiana anormal da PA em pacientes internados no hospital com um evento cardiovascular recente ainda não foi estudado. O escore do estudo Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) é um dos sistemas de escore angiográfico coronariano detalhado mais aceito para determinar a gravidade e a complexidade da doença arterial coronariana (DAC), dependendo da anatomia coronariana e características da lesão.16 O presente estudo visou avaliar a relação entre o escore SYNTAX e menor dipping noturno da PA com uso frequente de MCPA  em pacientes hospitalizados com síndrome coronariana aguda (SCA).Embora os distúrbios diurnos da PA estejam ligados a danos em diversos órgãos e eventos cardiovasculares, o mecanismo subjacente não é claro.17 Os pacientes que haviam recebido tratamento anti-hipertensivo anteriormente continuaram os mesmos tratamentos durante todo o período de acompanhamento. Demos medicamentos anti-hipertensivos a todos os pacientes nos horários da manhã sem alterar o seu uso. A hipercolesterolemia foi definida como colesterol total > 200 mg/dl. A taxa de filtração glomerular estimada foi calculada usando a fórmula de Cockcroft-Gault.18 Excluímos pacientes com qualquer uma das condições a seguir: apresentando choque ou parada cardiogênica, recebendo nitroglicerina intravenosa ou terapia inotrópica por qualquer motivo, histórico de enxerto de bypass de artéria coronária, valvulopatias, malignidade, doença renal ou hepática, insuficiência cardíaca sintomática, hipertensão secundária, arritmia não controlada, angina ou ansiedade contínua, síndrome da apneia obstrutiva do sono ou distúrbio do sono e obesidade mórbida . Por fim, a população do estudo consistiu em 141 pacientes clinicamente estáveis, incluindo 85 com IAMSSST, 15 com angina pectoris instável e 41 com IAMCSST , que haviam sido submetidos à angiografia coronária. Foram aferidos parâmetros bioquímicos, incluindo colesterol total, lipoproteína de baixa densidade (LDL), lipoproteína de alta densidade (HDL), triglicerídeos e testes de função renal. Foram medidos os parâmetros hematológicos como parte do hemograma completo automatizado . A hipertensão foi diagnosticada e estratificada de acordo com as diretrizes recentes. IAMCSST . A idade16Todos os pacientes foram submetidos à angiografia coronária em 24 horas. O tempo médio dos sintomas até a angiografia coronária foi de aproximadamente 2 a 6 horas. Foi realizada a angiografia coronária pela técnica padrão de Judkins utilizando cateteres de 6 ou 7 Fr  através da artéria femoral. Quando necessária, a intervenção coronária percutânea para a lesão culpada foi realizada com sucesso em pacientes elegíveis na mesma sessão . O escore SYNTAX foi calculado usando uma calculadora online conforme descrito na literatura de acordo com os achados angiográficos basais por 2 operadores experientes que desconheciam os demais parâmetros.Na nossa clínica, os pacientes com SCA são acompanhados na unidade de terapia intensiva pelo menos nas primeiras 24 horas após a intervenção coronária percutânea. No entanto, pacientes estáveis de baixo risco  são mobilizados e acompanhados na unidade de terapia intensiva intermediária ao final de 24 horas. A nossa população de estudo foi selecionada a partir desses pacientes e foram realizadas medidas de PA de hora em hora na unidade de terapia intensiva intermediária com um dispositivo automático de medição de PA em monitores de beira de leito para todos os pacientes . As medidas foram feitas no membro superior usando 2 manguitos infláveis (22 × 12 e 30 × 14 cm) para cobrir pelo menos 80% da circunferência do braço do paciente. Foi garantida a acurácia da medição otimizando todos os monitores dos pacientes antes das primeiras medições e comparando-os com medições de esfigmomanômetros de padrão calibrados. Ao permitir que os pacientes dormissem em suas camas às 23:00 h e acordassem às 7:00 h, os valores noturnos da PA foram obtidos por medição a cada hora. Informamos a todos os pacientes antes do procedimento e realizamos todas as medidas da PA noturna enquanto os pacientes dormiam.Excluímos a medida se o paciente acordasse por qualquer motivo, e a medida foi repetida imediatamente após o paciente dormir. Beber café, fumar e fazer exercícios não foram permitidos antes da medição; após sentar e descansar por 5 minutos, a PA diurna foi obtida pela medida da PA a cada hora entre 08:00 h e 22:00 h com o mesmo aparelho, em decúbito dorsal. Para todas as medições, os monitores dos pacientes foram configurados para medir em intervalos de 1 hora. O mesmo profissional de saúde experiente verificou os pacientes em termos de estado de sono-vigília, adequação do manguito e posição do paciente durante a medição; as medidas noturnas da PA foram registradas sob luz fraca, sem acender totalmente as luzes da unidade de terapia intensiva intermediária. Caso o paciente fosse transferido para a unidade de terapia intensiva intermediária em horário que não correspondesse ao início dos períodos de medição, iniciamos as medições no primeiro período seguinte (23:00 da noite ou 7:00 do dia). Os pacientes foram acompanhados na unidade de terapia intensiva intermediária durante pelo menos 24 horas. Valores extremos de PA  foram considerados errôneos e não foram incluídos na análise. Considerando as médias dos valores horários de PA para 9 períodos noturnos (23:00 h às 07:00 h) e 15 períodos diurnos (8:00 h às 22:00 h), obteve-se um único valor médio de PA diurna e noturna. A queda da PA sistólica noturna para diurna foi calculada como 100 × ([média da PA sistólica diurna – média da PA sistólica noturna]/média da PA sistólica diurna]). A redução da PA durante a noite em relação ao dia foi definida da maneira seguinte: dipping normal quando estava entre 10% e 20%, não-dipping quando < 10% e dipping reverso quando houve algum aumento .Foi realizado o exame ecocardiográfico com um sistema de ultrassom cardiovascular disponível comercialmente . Foi realizada a aquisição de dados com um transdutor de 1,5 a 2,6 MHz nas cortes paraesternal e apical (visão padrão de 2 e 4 câmaras). Foram obtidas imagens bidimensionais e Doppler enquanto os pacientes estavam prendendo a respiração e armazenadas em formato cine-loop a partir de 3 batimentos consecutivos; valores médios foram relatados e os eletrocardiogramas foram registrados simultaneamente. A fração de ejeção do ventrículo esquerdo foi derivada pela regra de Simpson modificada biplano e apical. As medidas do Doppler incluíram a velocidade de pico de enchimento mitral precoce (onda E), a velocidade de pico de enchimento mitral tardia (onda A) e a relação entre as velocidades de pico de enchimento mitral precoce e tardia (E/A). Para as velocidades do tecido miocárdico, o volume da amostra de imagem do Doppler tecidual foi colocado no anel mitral lateral na junção entre o corte da parede lateral do ventrículo esquerdo e o corte apical de 4 câmaras do anel mitral. A imagem Doppler tecidual incluiu os seguintes parâmetros: velocidade miocárdica diastólica precoce (Em), velocidade miocárdica diastólica tardia (Am) e Em/Am. Todos os ecocardiogramas foram interpretados por 2 cardiologistas experientes cegos ao estado do paciente.O SPSS 21.0 for Windows  foi utilizado para as análises estatísticas. Os dados quantitativos foram expressos como média ± desvio padrão. Os dados categóricos foram apresentados como número e frequência (%). Para a técnica de análise adequada, foram aplicados os testes de Kolmogorov–Smirnov e de homogeneidade de variância. Foram usados testes t de amostras independentes para comparação de 2 grupos das variáveis normalmente distribuídas e foi usado o teste U de Mann-Whitney para comparação de 2 grupos das variáveis sem distribuição normal. As variáveis com distribuição não normal foram expressas como medianas . As variáveis contínuas normalmente distribuídas foram expressas como média ± desvio padrão. As variáveis categóricas foram comparadas pelo teste de qui-quadrado. Os preditores independentes do escore SYNTAX foram avaliados por meio de análise de regressão logística multivariada. No procedimento multivariado, idade, sexo, índice de massa corporal, histórico de hipertensão e diabetes mellitus, tabagismo, taxa de filtração glomerular, níveis de colesterol LDL e hipertensão não-dipper foram as variáveis clínicas consideradas. P < 0,05 foi considerado estatisticamente significativo.Neste estudo, foram selecionados 306 pacientes consecutivos com SCA. Após a exclusão dos pacientes que preencheram os critérios de exclusão, os 141 pacientes restantes  foram incluídos no estudo . IAMCSSTOs pacientes foram agrupados de acordo com tercis do escore SYNTAX mediano definidos da forma seguinte: pontuação SYNTAX baixa < 8  e pontuação SX alta ≥ 8 . O número de pacientes com escores altos foi significativamente maior no grupo de hipertensão não-dipper em comparação com o grupo de hipertensão dipper . Em um mOs nossos resultados sugeriram uma associação significativa entre a menor redução da PA sistólica noturna (hipertensão não-dipper) na MCPA frequente e a gravidade e complexidade da DAC calculada pelo escore SYNTAX em pacientes hospitalizados por SCA. Além disso, verificamos que a hipertensão não-dipper foi um indicador independente de escore SYNTAX mais alto nessas populações de pacientes.19 relataram que menor redução da PA noturna estava associada a maior prevalência de acidente vascular cerebral. Descreveram essa anormalidade circadiana da PA como hipertensão não-dipper. Desde então, um número crescente de relatos têm publicado que existe uma estreita relação entre hipertensão não-dipper e aumento da morbimortalidade cardiovascular.7 Em uma metanálise recente, o estudo ABC-H7 avaliou o seguimento de 8 anos de 17.312 pacientes com hipertensão. O padrão não-dipping, após ajuste para PA sistólica de 24 horas, foi um preditor de excesso de risco variando de 33% para mortalidade por todas as causas a 57% para mortalidade cardiovascular. Mousa et al.20 demonstraram uma associação significativa entre hipertensão não-dipper e DAC significativa (≥ 70% de estenose de artéria coronária na angiografia) independente de outros parâmetros clínicos em homens. Wirtwein et al.21 relataram que a extensão da estenose significativa da artéria coronária (≥ 50% de estenose em pelo menos três artérias coronárias na angiografia) e eventos cardiovasculares adversos maiores estavam relacionados a dipping reduzido da PA sistólica noturna.Pela primeira vez, O’Brien et al.27 A diminuição do tônus arterial à noite faz com que a PA pulsátil seja transmitida à microcirculação de forma mais eficaz do que durante o dia e interrompe o fluxo laminar fisiológico. Como resultado, as células endoteliais arteriais são expostas a estresse de cisalhamento oscilante; a biodisponibilidade do óxido nítrico diminui; o estresse oxidativo aumenta e a disfunção endotelial, que é o primeiro passo no desenvolvimento da aterosclerose, é estimulada.29 As lesões coronarianas complexas avaliadas pelo escore SYNTAX, como ramos, bifurcações e curvaturas, estão intimamente relacionadas ao estresse de cisalhamento oscilante, apoiando essa hipótese.30 Demonstramos anteriormente que, em pacientes com SCA, os marcadores de estresse oxidativo aumentaram significativamente na DAC intensiva avaliada pelo escore de Gensini.31 Além disso, mostrou-se que precursores de trombogênese como fator de von Willebrand, D-dímero, fibrinogênio e P-selectina são significativamente aumentados em pacientes com hipertensão não-dipper e DAC, apoiando o mecanismo associado à SCA.32 Também encontramos uma porcentagem maior de IAMCSST em pacientes com hipertensão não-dipper, nos quais a trombose é mais proeminente na sua fisiopatologia do que em outros tipos de SCA.33Embora a estreita correlação entre hipertensão não-dipper e eventos cardiovasculares adversos maiores tenha sido demonstrada em muitos estudos diferentes, o mecanismo fisiopatológico subjacente permanece incerto. Foi comprovado que o escore SYNTAX reflete eventos cardiovasculares adversos maiores, como na hipertensão não-dipper. Portanto, os resultados do nosso estudo podem fornecer evidências adicionais para tal correlação ao revelar DAC mais intensa e mais complexa calculada pelo escore SYNTAX em pacientes com SCA e hipertensão não-dipper. Entre os mecanismos mais enfatizados na patogênese estão a mudança para hiperatividade simpática no sistema nervoso autônomo à noite, disfunção dos barorreceptores arteriais, labilidade elevada de repolarização miocárdica, aumento da sensibilidade ao sódio, aumento da rigidez arterial, inflamação crônica de baixo grau e disfunção endotelial.8 mediram, com esfigmomanômetro manual, 6 vezes ao dia, em intervalos de 4 horas em pacientes hospitalizados, os valores que denominaram MCPA em comparação com a MAPA tradicional de 24 horas. Os pesquisadores relataram uma forte correlação entre a PA clínica e ambulatorial para a PA sistólica e diastólica. Além disso, declararam que a detecção de não-dipper pela MCPA estava bem de acordo com a MAPA de 24 horas. Além disso, desde que um monitor automático de pressão arterial domiciliar foi desenvolvido pela primeira vez em 2001 e usado para monitorazação noturno da PA em um estudo, muitos estudos confirmaram uma forte correlação entre as medidas de MAPA e MDPA. Tem sido relatado na literatura que a MDPA pode ser uma alternativa confiável à MAPA para avaliar a PA noturna e detectar hipertensão não-dipper.34 Recentemente, os dados do estudo J-HOP Nocturnal BP, a maior coorte de MDPA baseada na prática, mostraram que um aumento de 10 mmHg na PA sistólica noturna, na MDPA, foi associado a um aumento significativo de 20,1% nos eventos cardiovasculares adversos maiores, semelhantes àqueles medidos pela MAPA.35 Embora Xu et al.8 tenham calculado MCPA em pacientes hospitalizados, realizando 3 medições de PA diurnas e 3 noturnas em um único dia, na maioria dos estudos com MDPA, 3 medições de PA diurnas e 3 noturnas foram repetidas ao longo de 1 a 2 semanas e foram calculadas as médias. Para superar a permanência limitada na unidade de terapia intensiva intermediária e a falta de oportunidade de medir em dias repetidos sob as mesmas condições, realizamos a MCPA em intervalos frequentes (uma vez por hora) como uma combinação de ambos esses métodos no nosso estudo.A MAPA é considerada o padrão ouro para monitorização da PA noturna; no entanto, métodos alternativos começaram a se desenvolver, principalmente em pacientes hospitalizados, devido ao uso clínico limitado da MAPA, seu alto custo e o fato de interferir no conforto do sono. Xu et al.O nosso estudo possui algumas limitações:A reprodutibilidade não pôde ser analisada, pois foi possível medir a PA em apenas um dia. Para superar esse problema, usamos a MCPA frequente, um protocolo modificado de MCPA, no nosso estudo.Embora tenhamos prestado o máximo de atenção para garantir as condições e níveis de sono-vigília ideais, a qualidade do sono que poderia afetar a PA noturna não foi avaliada no nosso estudo.Mesmo com os dois grupos comparados estando nas mesmas condições, o período de hospitalização imediatamente após a SCA pode afetar o estado de estresse e o sistema nervoso autônomo dos pacientes, causando resultados diferentes da condição estável.Os resultados do nosso estudo revelaram a relação entre o escore SYNTAX e a hipertensão não-dipper em pacientes com SCA, até onde sabemos pela primeira vez, fornecendo um possível mecanismo adicional ligando a PA circadiana anormal a doenças cardiovasculares. Estudos futuros são necessários para melhor compreensão dessa associação e determinar as abordagens necessárias para a PA diurna ideal. Duração mais longa e múltiplas múltiplas medições pressóricas de 24 horas podem ser mais informativas a esse respeito. 1 Blunted nocturnal BP reduction is a strong predictor of cardiovascular morbidity and mortality for patients with and without hypertension.7 The standard method for determining non-dipper and dipper patterns in patients is 24-hour non-invasive ambulatory blood pressure monitoring (ABPM), which is generally performed out of the office. On the other hand, alternatively, clinical blood pressure monitoring (CBPM) in hospitalized patients and home blood pressure monitoring (HBPM) in outpatients are performed with infrequent manual or automatic BP measurements. CBPM and HBPM have previously shown to have daytime and nighttime BP measurements similar to ABPM in hospitalized patients and outpatients and to be consistent with ABPM in demonstrating non-dipper hypertension.10Physiological blood pressure (BP) exhibits a circadian pattern with a decrease of 10% to 20% during sleep in relation to daytime BP. This decrease during sleep is defined as extreme dipping if ≥ 20%, normal dipping if 10% to 20%, non-dipping if < 10%, and reverse dipping if there is any increase .13 However, the clinical significance of abnormal circadian BP variation in patients admitted to the hospital with a recent cardiovascular event has not yet been studied. The Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery Study (SYNTAX) score (SX score) is one of the most accepted detailed coronary angiographic scoring systems for determining the severity and complexity of coronary artery disease (CAD), depending on coronary anatomy and lesion characteristics.16 This study aimed to evaluate the relationship between SX score and blunted nighttime BP dipping using frequent CBPM  in hospitalized patients with acute coronary syndrome (ACS).Although diurnal BP disorders are linked to damage of several organs and cardiovascular events, the underlying mechanism is unclear.17 Patients who had previously received antihypertensive treatment continued the same treatments throughout the follow-up period. We gave antihypertensive medicines to all patients in the morning hours without changing their usage. Hypercholesterolemia was defined as total cholesterol > 200 mg/dl. The estimated glomerular filtration rate was calculated using the Cockcroft-Gault formula.18 We excluded patients with any of the following: presenting with cardiogenic shock or arrest, receiving intravenous nitroglycerine or inotrope therapy for any reason, history of coronary artery bypass grafting, valvular heart disease, malignancy, renal or hepatic disease, symptomatic heart failure, secondary hypertension, uncontrolled arrhythmia, ongoing angina or anxiety, obstructive sleep apnea syndrome or sleep disorder, and morbid obesity (body mass index > 35). Finally, the study population consisted of 141 clinically stable patients, including 85 with NSTEMI, 15 with USAP, and 41 with STEMI . Biochemistry parameters, including total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, and renal function tests, were measured. Hematological parameters were measured as a part of the automated complete blood count . Hypertension was diagnosed and stratified based on recent guidelines.th STEMI . Patient16All patients underwent coronary angiography within 24 hours. The average time from symptoms to coronary angiography was approximately 2 to 6 hours. Coronary angiography was performed by the standard Judkins technique using 6 or 7 French catheters  through the femoral artery. When necessary, percutaneous coronary intervention for the culprit lesion was successfully performed on eligible patients in the same session . SX score was calculated with an online calculator as described in the literature according to the basal angiographic findings by 2 experienced operators who were blind to other parameters.In our clinic, patients with ACS are followed up in the intensive care unit for at least the first 24 hours after percutaneous coronary intervention. However, low-risk stable patients  are mobilized and followed up in the intermediate intensive care unit at the end of 24 hours. Our study population was selected from these patients, and hourly BP measurements were made in the intermediate intensive care unit with an automatic BP measurement device on bedside monitors for all patients . Measurements were made in the upper limb using 2 inflatable cuffs (22 × 12 and 30 × 14 cm) to cover at least 80% of the patient’s arm circumference. Measurement accuracy was ensured by optimizing all patient monitors before the first measurements and comparing them with calibrated standard sphygmomanometer measurements. By enabling the patients to sleep in their beds at 23:00 and wake up at 7:00, nighttime BP values were obtained by hourly measurement. We informed all patients before the procedure and took all nighttime BP measurements while the patients were sleeping.We excluded measurement if the patient awoke for any reason, and the measurement was repeated immediately after the patient slept. Coffee drinking, smoking, and exercise were not allowed before measurement; after sitting and resting for 5 minutes, daytime BP was obtained by measuring BP hourly between 08:00 and 22:00 with the same device in the supine position. For all measurements, patient monitors were set to measure at 1-hour intervals. The same experienced healthcare personnel checked the patients in terms of sleep-wake status, cuff appropriateness, and patient position during measurement; nighttime BP measurements were recorded under dim light, without fully turning on the intermediate intensive care unit lights. If the patient was transferred to the intermediate intensive care unit at a time that did not correspond to the beginning of the measurement periods, we started the measurements in the first following period (23:00 at night-time or 7:00 the daytime). Patients were followed up in the intermediate intensive care unit for at least 24 hours. Extreme BP values  were considered as erroneous measurement and were not included in the analysis. By averaging the hourly BP values for 9 nighttime periods (23:00 to 07:00) and 15 daytime periods (8:00 to 22:00), a single daytime and nighttime mean BP value was obtained. Nighttime to daytime systolic BP dip was calculated as 100 × ([day-time systolic BP mean – nighttime systolic BP mean]/daytime systolic BP mean]). Decrease in BP at nighttime compared to daytime was defined in the following manner: normal dipping if 10% to 20%, non-dipping if < 10%, and reverse dipping if there was any increase .Echocardiographic examination was performed with a commercially available cardiovascular ultrasound system . Data acquisition was performed with a 1.5 to 2.6 MHz transducer in the parasternal and apical views (standard 2- and 4-chamber views). Two-dimensional and Doppler images were obtained during breath-hold and stored in cine-loop format from 3 consecutive beats; average values were reported, and electrocardiograms were simultaneously recorded. Left ventricle ejection fraction was derived by the apical biplane modified Simpson rule. Doppler measurements included peak early mitral filling velocity (E wave), peak late mitral filling velocity (A wave), and the ratio of peak early and late mitral filling velocities (E/A). For myocardial tissue velocities, tissue Doppler imaging sample volume was placed at the lateral mitral annulus at the junction between the left ventricular lateral wall and mitral annulus apical 4-chamber view. Tissue Doppler imaging included the following parameters: early diastolic myocardial velocity (Em), late diastolic myocardial velocity (Am), and Em/Am. All echocardiograms were interpreted by two experienced cardiologists who were blind to patient status.SPSS 21.0 for Windows  was used for statistical analyses. Quantitative data were expressed as mean ± standard deviation. Categorical data were presented as number and frequency (%). For the suitable analysis technique, Kolmogorov–Smirnov and homogeneity of variance tests were applied. Independent sample t-tests were used for two-group comparison of the normally distributed variables, and Mann–Whitney U-test was used for two-group comparison of the variables without normal distribution. Non-normally distributed variables were expressed as medians (interquartile ranges). Normally distributed continuous variables were expressed as mean ± standard deviation. Categorical variables were compared using the chi-square test. Independent predictors of SX score were assessed using multivariable logistic regression analysis. In the multivariate procedure, age, sex, body mass index, history of hypertension and diabetes mellitus, smoking, glomerular filtration rate, LDL cholesterol levels, and non-dipper hypertension were the clinical variables considered. P < 0.05 was considered statistically significant.In this study, a total of 306 consecutive patients with ACS were screened. After excluding patients who met the exclusion criteria, the remaining 141 patients  were included in the study . STEMI, Patients were grouped according to median SX score tertiles defined as: low SX score < 8  and high SX score ≥ 8 . The number of patients with high scores was significantly higher in the non-dipper hypertension group compared to the dipper hypertension group . In a muOur results suggested a significant association between blunted nocturnal systolic BP reduction (non-dipper hypertension) on frequent CBPM and the severity and complexity of CAD calculated by SX score among patients hospitalized for ACS. Also, we found that non-dipper hypertension was an independent indicator of higher SX score in these patient populations.19 reported that the blunted decrease in nighttime BP was associated with a higher prevalence of stroke. They described this circadian BP abnormality as non-dipper hypertension. Since then, a growing number of reports have published that there is a close relationship between non-dipper hypertension and increased cardiovascular morbidity and mortality.7 In a recent meta-analysis, the ABC-H7 study evaluated the 8-year follow-up of 17,312 hypertension patients. The non-dipping pattern, after adjustment for 24-hour systolic BP, predicted an excess risk ranging from 33% for all-cause mortality to 57% for cardiovascular mortality. Mousa et al.20 showed a significant association between non-dipper hypertension and significant CAD (≥ 70% coronary artery stenosis on angiography) independent of other clinical parameters in men. Wirtwein et al.21 reported that extent of significant coronary artery stenosis (≥ 50% stenosis in at least three coronary arteries on angiography) and major adverse cardiovascular events were related to blunted nighttime systolic BP dipping.For the first time, O’Brien et al.27 Decreased arterial tone at night causes pulsatile BP to be transmitted to microcirculation more effectively than during the day and disrupts the physiological laminar flow. As a result, arterial endothelial cells are exposed to oscillatory shear stress; nitric oxide bioavailability decreases; oxidative stress increases, and endothelial dysfunction, which is the first step in the development of atherosclerosis, is stimulated.29 Complex coronary lesions assessed by SX score, such as branches, bifurcations, and curvatures, are closely related to oscillating shear stress, supporting this hypothesis.30 We have previously shown that, in patients with ACS, oxidative stress markers significantly increased in intensive CAD assessed by the Gensini score.31 Moreover, precursors of thrombogenesis such as von Willebrand factor, D-dimer, fibrinogen, and P-selectin have been shown to be significantly increased in patients with non-dipper hypertension and CAD, supporting the mechanism associated with ACS.32 We also found a higher percentage of STEMI in patients with non-dipper hypertension, in which thrombosis is more prominent in its pathophysiology than in other ACS types.33Although the close correlation between non-dipper hypertension and major adverse cardiovascular events has been demonstrated in many different studies, the underlying pathophysiological mechanism remains unclear. SX score has been proven to reflect major adverse cardiovascular events as in non-dipper hypertension. Therefore, the results of our study may provide additional evidence for such correlation by revealing more intense and more complex CAD calculated by SX score in patients with ACS and non-dipper hypertension. Among the most emphasized mechanisms in pathogenesis are the shift to sympathetic overactivity in the autonomic nervous system at night, arterial baroreceptor dysfunction, elevated myocardial repolarization lability, increased sodium sensitivity, increased arterial stiffness, chronic low-grade inflammation, and endothelial dysfunction.8 measured, with a manual sphygmomanometer, 6 times a day at 4-hour intervals in hospitalized patients the values they called CBPM compared with traditional 24-hour ABPM. The investigators reported a strong correlation between clinical and ambulatory BP for both systolic and diastolic BP. Also, they declared that the detection of non-dippers by CBPM was in good agreement with 24-hour ABPM. Moreover, since an automatic home blood pressure monitor was first developed in 2001 and used for nighttime BP monitoring in a study, many studies have confirmed a strong correlation between APBM and HBPM measurements. It has been reported in the literature that HBPM can be a reliable alternative to ABPM to evaluate nighttime BP and detect non-dipper hypertension.34 Recently, the J-HOP Nocturnal BP Study data, the largest practice-based HBPM cohort, showed that a 10 mmHg increase in nighttime systolic BP in HBPM was associated with a significant 20.1% increase in major adverse cardiovascular events, similar to those measured by ABPM.35 Although Xu et al.8 calculated CBPM in hospitalized patients by taking 3 daytime and 3 night-time BP measurements in a single day, in most HBPM studies, 3 daytime and 3 night-time BP measurements were repeated over 1 to 2 weeks and averaged. To overcome limited stay in the intermediate intensive care unit and the lack of opportunity to measure on repeated days under the same conditions, we performed CBPM at frequent intervals (once an hour) as a combination of both of these methods in our study.ABPM is considered the gold standard for monitoring nighttime BP; however, alternative methods have begun to develop, especially in hospitalized patients, due to the limited clinical use of ABPM, its high cost, and the fact that it disrupts sleep comfort. Xu et al.Our study has some limitations:Reproducibility could not be analyzed, as it was possible to measure BP for only one day. To overcome this problem, we used frequent CBPM, a modified CBPM, in our study.Although we paid the maximum attention to ensure optimal conditions and sleep-wake levels, sleep quality that could affect nighttime BP was not evaluated in our study.Even if both groups compared were in the same conditions, the hospitalization period immediately after ACS might affect the patients’ stress state and autonomic nervous system, causing different results from the stable condition.Our study results revealed the relationship between SX score and non-dipper hypertension in patients with ACS, to the best of our knowledge for the first time, providing a possible additional mechanism linking abnormal circadian BP with cardiovascular diseases. Further studies are needed to clarify this association and determine the approaches required for optimal diurnal BP. Longer duration and multiple 24-hour BP measurements may be more informative in this regard.


The objective of the study was to optimize the method of measuring left ventricular end-diastolic diameter (LVEDD) in cardiac magnetic resonance (CMR) as a predictor of left ventricular end-diastolic volume (LVEDV). The study group consisted of 78 patients (age 55.28 ± 17.18) who underwent 1.5 T CMR examination. LVEDD measurements in the short axis, in the long axis in the 2-chamber, 3-chamber and 4-chamber views were made by 2 radiologists. The repeatability of LVEDD measurements was assessed. The sensitivity and specificity of various methods of measuring LVEDD as a predictor of left ventricular enlargement (diagnosed based on LVEDV) were assessed. The correlation coefficients between LVEDD measurements made by researcher A and B were 0.98 for the long axis measurements in the 2-chamber and 3-chamber view, and 0.99 for measurements made in the short axis and in the long axis in the 4-chamber view. The lowest LVEDD measurements variability was recorded for the short axis measurements , and the highest for the long axis measurements in the 3-chamber view . In the male subgroup, the highest accuracy in predicting left ventricular enlargement was characterized by the criterion “LVEDD measured in the long axis in the 2-chamber view > 68.0 mm” (accuracy 94.1%). In the female subgroup, the highest accuracy in predicting left ventricular enlargement was achieved by the criterion “LVEDD measured in the short axis > 63.5 mm” (96.3%). In summary, the measurement made in the short axis should be considered the optimal method to LVEDD measure in CMR, considering the repeatability of measurements and the accuracy of left ventricular enlargement prediction. Left ventricular enlargement can be physiological (athlete’s heart) or pathological. We can distinguish primary causes (enlargement related directly to the pathology of the left ventricular myocardium) and secondary causes (enlargement developing because of pathology not directly related to the left ventricular myocardium) of left ventricular enlargement3. The primary causes of left ventricular enlargement may be manifested by left ventricular myocardial hypertrophy (hypertrophic cardiomyopathy) and left ventricular dilatation (dilated cardiomyopathy)4. Secondary left ventricular enlargement may occur as a result of increased preload or afterload, i.e., volume or pressure overload. The most common causes of left ventricular enlargement in the pathomechanism of volume overload include mitral and aortic valve insufficiency, ventricular septal defect, and patent ductus arteriosus. The causes of left ventricular enlargement due to pressure overload include arterial hypertension, aortic stenosis and aortic coarctation5.Left ventricular enlargement, i.e. increasing the dimensions of the left ventricle, is one of the common organic pathologies of the heart, the aetiology of which is heterogeneous and the pathophysiology of which is complex6. Echocardiography is a routine, widely available and standardized method. To diagnose left ventricular enlargement in echocardiography, the criterion of left ventricular end-diastolic diameter (LVEDD) is used measured in M-Mode or directly in 2D in the parasternal long axis view, exceeding 58.4 mm in men and 52.2 mm in women7. MRI is the “gold standard” in the assessment of the morphology and function of the heart, mainly due to the clearly better differentiation of the anatomical boundary between the endocardium and the lumen of the left ventricle8. In the assessment of cardiac magnetic resonance (CMR), left ventricular enlargement is most often diagnosed based on the left ventricular end-diastolic volume (LVEDV), the normative values of which were determined independently for different gender and age, both for absolute values and values indexed in relation to the body surface area9.The diagnosis of left ventricular enlargement is based on imaging methods, most often echocardiography and magnetic resonance imaging (MRI), although other diagnostic imaging methods may also be usefulAssessment of LVEDV, despite the continuous development of equipment and MRI applications, still requires dedicated technical solutions, manual verification of the semi-automatic estimation and experience of the assessor. Moreover, it is time consuming. While numerous attempts are being made to introduce artificial intelligence algorithms into the functional assessment of cardiac cavities, so far fully automated, precise and completely repeatable algorithms are a goal rather than a widely available clinical practice. Measurement of left ventricular end-diastolic diameter, a parameter routinely used in echocardiography, is relatively simple, not time-consuming and does not require dedicated tools. Even though the standard CMR assessment also includes linear measurements, including LVEDD measurement, the recommendations of scientific societies and research groups lack a standardized method of measuring this parameter. Obviously, no attempt should be made to replace a target LVEDV measurement with a LVEDD measurement. However, because the recipients of CMR results are cardiology clinicians who routinely use the LVEDD parameter in echocardiography, attempts should be made to standardize the LVEDD measurement. These tests should be aimed at minimizing the discrepancy of the LVEDD measurement with the LVEDV measurement. Therefore, it seems cognitively interesting and clinically necessary to verify the repeatability of various methods of LVEDD measuring in CMR, as well as to determine the accuracy of various methods of making this measurement as a predictor of LVEDV.The objective of the study was to optimize the method of LVEDD measuring in CMR as a predictor of LVEDV.The research has been conducted in compliance with the principles of Good Clinical Practice and Declaration of Helsinki. Ethics Committee of Wroclaw Medical University approved the experimental protocol (protocol code KB-414/2021). The written informed consent has been obtained from all the patients taking part in the research. All data collected from the patients were anonymized.The retrospective study included 78 consecutive patients who came to the MRI Laboratory of the Wroclaw Medical University for CMR in the period from November 15, 2020 to March 15, 2021. The mean age of the patients was 55.28 ± 17.18 years, the youngest patient was 22 years old, and the oldest was 87 years old. In the study group, 65.4% were men and 34.6% were women. The clinical indications constituting the reason why patients were referred for MRI included: heart failure (42 patients), cardiomyopathy (49) , myocarditis (9), coronary artery disease (15), arrhythmias (1), cardiac involvement in the course of systemic diseases (3) and pericardial pathologies (1). The characteristics of the study group are presented in Table To consider age and gender to optimize the method of LVEDD measuring in CMR as a predictor of LVEDV, subgroups were distinguished. Based on the gender criterion, a male subgroup (n = 51) and a female subgroup (n = 27) were established, while based on the age median (Me = 58 years), a group of patients aged < median  and a group of patients aged ≥ median  were established.CMR was performed using one 1.5 T Signa Hdx MRI  device. CMR was performed according to a standard protocol. ECG gating and breath hold during the gating were used. The study protocol included locating sequences, low-resolution single-shot black blood lookup sequences (Single Shot FSE), CINE steady-state free precession sequences (SSFP), T2 fat saturation sequences (T2fs), and late gadolinium enhancement sequences (IRPrepFGRE). The study protocol consisted of a bolus injection of gadobutrol  in the amount of 0.2 mmol/kg body mass through the ulnar fossa veins.CMR images obtained during the study were assessed using the GE ReportCARD Package , a standard application for CMR post-processing assessment provided by the MRI manufacturer. The standard assessment of CMR included the initial assessment of the mediastinal anatomy in the Single Shot FSE sequences, the assessment of the dimensions and volume of the heart chambers in the CINE sequences recorded in the short axis of the left ventricle and in the long axis in the 2-chamber, 3-chamber and 4-chamber views, and the assessment of morphological changes of the left ventricular myocardium (oedema and fibrosis) in T2fs and LGE sequences. In the standard CMR evaluation, the left atrium (LA) and the aortic root (Ao) dimensions were measured in the 3-chamber view; in the short axis view, the left ventricular end-diastolic diameter (LVEDD), anterior interventricular septum diastolic dimension (aIVSDD) and posterior wall diastolic dimension (PWDD) were measured in the basal-middle layers. Based on CINE images in the short axis of the left ventricle, the functional parameters of the left ventricle were measured using the volumetric method. Outlines of the epicardium and endocardium were made in successive layers of the short axis of the left ventricle in diastole and systole. Left ventricular end-diastolic and end-systolic volumes (LVEDV and LVESV) were calculated by summing the consecutive left ventricular lumen areas from the successive layers multiplied by the thickness of the layers. Left ventricular ejection fraction (LVEF) was calculated according to the mathematical formula: LVEF = (LVEDV − LVESV)/LVEDV × 100%. The application, considering the adopted standard myocardial density, estimated the left ventricular mass (LVM) based on the total volume of the left ventricular myocardium. Standard assessment of CMR was performed each time by one of two radiology and imaging diagnostics specialists with experience in the performance and interpretation of CMR reaching up to 150 examinations interpreted annually over the last 5–10 years.The CINE SSFP images obtained during CMR were used to retrospectively perform additional measurements of the left ventricular dimensions in diastole. In addition to LVEDD measured in the basal-middle layers in the short axis view, measurements of LVEDD were made in the long axis in the 2-chamber, 3-chamber and 4-chamber views. LVEDD in the long axis views was measured at 1/3 of the proximal distance of the mitral valve from the apex  + ((measurement B − X measurement)2))/2); absolute difference (AD): AD =|A measurement − B measurement|; relative difference (RD): RD = AD of measurement/X of measurement; and the coefficient of variation (CV): CV = (SD of measurement/X of measurement) × 100%.To assess the repeatability of the measurements of the left ventricular dimensions in diastole, secondary parametric variables were calculated, being the resultant of the measurement of LVEDD measured by researcher A and the measurement of the analogous diameter measured by researcher B. The calculated secondary variables and the formulas used to calculate them are as follows: mean measurement : X = (measurement A + measurement B)/2; standard deviation of the measurement : SD = √(((measurement A − X measurement)The statistical evaluation of the results was performed with the use of the “Dell Statistica 13” program . Quantitative variables were characterized by arithmetic means and standard deviations. The results for the qualitative variables were characterized by percentage values. The Shapiro–Wilk W test was used to assess the distribution of variables. In comparative analyses, the test for unrelated variables  or the Mann–Whitney U test  was used to test the hypotheses. To determine the correlations between the studied variables, the Pearson or Spearman correlation analysis and the univariate regression analysis were performed. Moreover, the sensitivity and specificity analysis were performed with the use of ROC (Receiver Operating Characteristic) curve analysis. The results at the levels p < 0.05 were considered statistically significant.All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of Wroclaw Medical University (protocol code KB-414/2021) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.Informed consent was obtained from all individual participants included in the study.Analysing LVEDD measurements, no statistically significant differences were observed between the mean measurements made by researcher A and researcher B. The correlation coefficients between LVEDD measurements made by researcher A and researcher B were 0.98 for the long axis measurements in the 2-chamber and 3-chamber view, and 0.99 for measurements made in the short axis and in the long axis in the 4-chamber view. The mean values of LVEDD measured in the short axis and in the long axis in the 2-chamber view were about 20% greater than those measured in the long axis in the 3-chamber and 4-chamber view . The smallest absolute difference in the measurement concerned the measurement made in the short axis (1.10 mm), and the largest absolute difference in the measurement made in the long axis in the 2-chamber view (1.95 mm). In terms of objectified parameters characterizing the repeatability of the measurements, i.e. the relative difference and the coefficient of variation, the lowest values were recorded for the short axis measurements , and the highest for the long axis measurements in the 3-chamber view . The results of analysing the repeatability of LVEDD measurements in CMR are presented in Table Comparing the parameters characterizing the repeatability of LVEDD measurements in CMR, no significant differences were found between the subgroups established based on gender and age median. Gender and age did not affect the repeatability of LVEDD measurements made by researcher A and researcher B. The results of the analysis of the repeatability of LVEDD measurements in CMR in the subgroups established based on gender are presented in Table Correlation analysis showed the existence of statistically significant positive linear relationship between LVEDD measured using each of the assessed methods and LVEDV. Correlation coefficients, depending on the method of LVEDD measuring and the researcher who made the measurements, ranged from 0.81 to 0.84. The complete results of the correlation analysis in the study group are presented in Table LVEDV [ml] = 4.561 LVEDD measured in the short axis [mm] − 116.278 (corrected R2: 0.83)LVEDV [ml] = 4.612 LVEDD measured in the long axis in the 2-chamber view [mm] − 116.259 (corrected R2: 0.82)LVEDV [ml] = 4.898 LVEDD measured in the long axis in the 3-chamber view [mm] − 103.513 (corrected R2: 0.83)LVEDV [ml] = 4.626 LVEDD measured in the long axis in the 4-chamber view [mm] − 89.801 (corrected R2: 0.83)Using the univariate regression analysis, mathematical formulas were created, by means of which, based on the measured left ventricular end-diastolic diameters, the value of the LVEDV can be estimated:Using the sensitivity and specificity analysis, the accuracy of LVEDD (assessed by various means) as a predictor of left ventricular enlargement (diagnosed based on LVEDV in CMR) was evaluated. LVEDD measurement values representing the optimal cut-off points for the prediction of left ventricular enlargement in the male subgroup Fig. A–D and iLVEDD measurements by CMR by 2 different researchers are highly reproducible. The repeatability of LVEDD measurements by 2 researchers is high, regardless of the method used to measure it. Measurements made by different researchers are strongly correlated with each other, they do not differ statistically from each other, and their coefficients of variation are in the range of 1.38–2.53%. Based on the obtained results, it can be indicated, however, that the optimal way to LVEDD measure in CMR (due to its highest repeatability) is the measurement carried out in the short axis. The objectified parameters characterizing the repeatability of the measurements were the lowest. The repeatability of LVEDD measurements by MRI is independent of gender and age. At the same time, it should be remembered that, depending on the method of measuring left ventricular end-diastolic diameter, MRI results in values that differ by up to 20%. Based on the obtained results, it is impossible to clearly define which of the assessed methods of LVEDD measuring by MRI is the optimal method in the context of predicting left ventricular enlargement. The correlation coefficients between LVEDD measured by various methods and LVEDV were similar, and the accuracy of subsequent predictors suggested by the analysis of ROC curves in the studied male subgroup was within a narrow range of 88.2–94.1%. The varied accuracy of successive predictors suggested based on the analysis of ROC curves in the studied female subgroup, ranging from 48.1 to 96.3%, different from that obtained in the male subgroup, has limited reliability. It results from the extremely small subgroup of patients with diagnosed left ventricular enlargement, amounting to 2 cases among the women participating in the study. To sum up, considering the repeatability of measurements and the accuracy of the prediction of left ventricular enlargement, the measurement in the short axis should be considered the most appropriate method to LVEDD measure in MRI. At the same time, it should be noted that measurements in the long axis do not give significantly different results, assuming the use of different cut-off points when diagnosing left ventricular enlargement.The issue of repeatability of measurements in diagnostic tests is one of the key issues in the context of their clinical usefulness. Despite numerous scientific studies on the repeatability of MRI measurements, the issue of the repeatability of LVEDD measurements has not been discussed so far.10. In their studies the main goal of which was to establish normative values for MRI of ventricular volume and mass in children, Buechel et al. showed that the variability of measurements between different researchers reaches 7% in the case of the left ventricle and 10% in the case of the right ventricle11. Also, Blalock et al. in a study dedicated to the assessment of the variability of the parameters of ventricular dimensions and function in MRI, indicated a greater variability in the measurements of the right ventricle, especially in the measurements of the right ventricular mass made based on images obtained in diastole12.In the existing scientific literature, most attention in the research on the variability of measurements in CMR has been devoted to the issue of estimating the volume of the left and right ventricles and the mass of the left ventricular myocardium. Already in the 1990s, Mogelvang et al. made attempts, indicating that lower variability is observed for the estimation of left ventricular mass than its volume. At the same time, these studies emphasized that the boundaries of consistency between different methods of estimation are too broad to accept clinically interchangeable use of different evaluation methods13. Interesting data on the discussed issue was provided by the publication of Karamitsos et al., who attempted to compare the repeatability of left ventricle mass and function measurements between experienced and inexperienced researchers, as well as to assess the impact on the discussed repeatability of brief intensive training of inexperienced researchers. This type of training improved the variability of left ventricular ejection fraction assessment from 7.2 to 3.7% and left ventricular mass from 7.7 to 6.7%14. In the light of the above-mentioned studies, the variability of LVEDD measurement obtained in our study, is a variability which may be considered as possible to omit, but at the same time indicates the optimal method of measurement.Optimistic data on the significance of the observed variability in the measurements of left ventricular volume, mass and ejection fraction was provided by the study conducted by Moody et al., which documented that short-term measurement errors between examinations do not differ significantly from long-term changes observed over a year. Thus, it was shown that the variability of left ventricle volume and mass measurements from MRI, resulting from technical factors, remains minimal, and even slight temporal changes in these parameters can be attributed to pathogensAn attempt to optimize the method of LVEDD measuring in the context of the accuracy of LVEDV prediction in the existing literature, according to the authors’ knowledge, has not been undertaken.15. It is worth mentioning that, as documented in the study by Polte et al., the underestimation of echocardiographic measurements of left ventricular dimensions increases successively from linear, through superficial, to volumetric measurements16. Disha et al. also noted that changes in the morphological and functional parameters of the left ventricle after aortic valve replacement have different dynamics depending on the native type of aortic valve: tricuspid and mitral17. The importance of LVEDD measuring in MRI may also be demonstrated by studies on the pathogenesis of myocardial infarction. Li et al. compared the predictive accuracy of CMR and echocardiography in interventional therapy in patients with acute myocardial infarction, showing that MRI parameters  are characterized by higher sensitivity and accuracy than the corresponding echocardiographic parameters18. Neuschl et al. analysed the correlation between left ventricular morphology and function in patients with severe post-infarction systolic dysfunction of the left ventricle with the presence of malignant arrhythmias. It has been documented that among the parameters of CMR, a lower LVEDD and a lower LVESD constitute risk factors for more frequent malignant arrhythmias in this group of patients19. In recent years, LVEDD has also been considered as one of the important parameters in studies on the determination of normative values for the assessment of the left ventricle by CMR. Macedo et al. stated that the normative values of measurements used in CMR mainly originate from studies conducted in North American and European populations. Therefore, they estimated such norms in the healthy Latin American population, showing values of 48 ± 5 mm for LVEDD20.At the same time, it should be noted that the above gap in the studies conducted so far may result from a significantly lower “popularity” of LVEDD as a parameter used in research with the use of CMR than, for example, in research where the method is based on echocardiography. In recent years, only a few published studies have paid more attention to the importance of LVEDD measuring in CMR. An important study of this type was the study conducted by Neisius et al., comparing the ability of MRI and echocardiography to predict left ventricular remodelling after aortic valve replacement. Linear measurement of left ventricular dimensions in echocardiography is used in assessing the severity of aortic valve disease. These studies show that echocardiography understates the LVEDD measurement by an average of 6.6 mm. Moreover, the correlation of left ventricular remodelling after aortic valve replacement with the severity of the aortic valve defect estimated by CMR was stronger than in the case of echocardiographyThe authors see several significant limitations in the currently discussed study. In terms of the study group, the relatively small number of patients included in the project, the overrepresentation of men in the study group and the heterogeneity of the group resulting from the presence of various disease entities and conditions in the study group should be considered as such. On the other hand, the methodological shortcomings of the study include the short period of time from which the results were analysed; use of LVEDV instead of LVEDV/BSA as the parameter based on which left ventricular enlargement, and the assumption of limiting the study to end-diastolic measurement instead of verifying the suitability of both end-diastolic and end-systolic measurements. The above limitations do not affect the usefulness of the conducted study but may constitute grounds for further research.The measurement made in the short axis should be considered the optimal method to LVEDD measure in CMR, considering the repeatability of measurements and the accuracy of left ventricular enlargement prediction.