Peak LV GCS and GRS decreased from controls to DCM (both p < 0.0001). The best value for differentiation between DCM and other groups was found for the LV ejection fraction (area under the curve (AUC) = 0.990, p = 0.0001, with 90.9% sensitivity and 100% specificity for ≤53%) and the peak LV GRS diastolic rate . The peak LV GRS diastolic rate was the only independent predictor of DCM (p = 0.003). Distinctive deformation patterns that were typical for each of the analysed groups existed and can help to differentiate between athlete’s heart, a nonathletic heart and a dilated cardiomyopathy.A better understanding of the left ventricle (LV) and right ventricle (RV) functioning would help with the differentiation between athlete’s heart and dilated cardiomyopathy (DCM). We aimed to analyse deformation parameters in endurance athletes relative to patients with DCM using cardiac magnetic resonance feature tracking (CMR-FT). The study included males of a similar age: 22 ultramarathon runners, 22 patients with DCM and 21 sedentary healthy controls (41 ± 9 years). The analysed parameters were peak LV global longitudinal, circumferential and radial strains ; peak LV torsion; peak RV GLS. The peak LV GLS was similar in controls and athletes, but lower in DCM ( It has been established that the hearts of endurance athletes undergo characteristic physiological remodelling, which primarily involves enlargement of all heart chambers and is sometimes accompanied by mild left ventricular hypertrophy, which is referred to as athlete’s heart (AH) ,2. In efAnother parameter, which could facilitate the differentiation of AH from DCM is a better understanding of the cardiac deformational mechanics in both groups ,10. ThesOn these grounds, we aimed to retrospectively analyse the rotational mechanics of the hearts of ultramarathon runners relative to both patients with DCM and nonathletic controls using CMR-FT. Our objective was to expand on what is known of myocardial contraction in these groups, as well as to identify parameters that bear a potential value in the discrimination between adaptive and maladaptive cardiac changes.The study included a group of 22 male amateur endurance athletes and a comparable number of sex- and age-matched patients with DCM, as well as healthy sedentary controls. The athletes were all long-term ultramarathon runners with at least 7 years of documented training, running an average of 70 km per week with frequent starts in competitions, which often exceeded 100 km in distance. They were all asymptomatic and free of cardiovascular disease, as verified using an electrocardiogram (ECG), cardiopulmonary exercise testing and CMR, which is presented in detail elsewhere . All pat®, Bayer Pharma AG, Berlin, Germany) flushed with 30 mL of isotonic saline. Late gadolinium enhancement (LGE) images in three long axes and a stack of short-axis imaging planes were obtained with a breath-hold segmented inversion recovery sequence performed 10 min after the contrast injection. The inversion time was adjusted to completely null the normal myocardium .The CMR imaging was performed using a Siemens Magnetom Skyra 3 T scanner in athletes and controls and with a Siemens Magnetom Avanto Fit 1.5 T scanner in patients with DCM . The protocol included initial scout images, followed by cine steady-state free precession (SSFP) breath-hold sequences in two-, three- and four-chamber views. The short axis was identified using the two- and four-chamber images and included the ventricles from the mitral and tricuspid valvular plane to the apex. This was followed by the administration of 0.1 mmol/kg of a gadolinium contrast agent  . An autoThe same contours were used for the analysis using CMR-FT. The peak global circumferential strain and global radial strains , and the peak GCS/GRS systolic and diastolic strain rates were derived from the analysis of a stack of short-axis slices. These images were also used to calculate the LV peak torsion and torsion rate, which reflects the difference between the clockwise rotation of the basal segments and the counterclockwise rotation of the apex during systole. The peak global longitudinal strain (GLS) and peak GLS systolic and diastolic strain rates of both ventricles were obtained from the combined analysis of three long-axis image projections.The presence and location of LGE was assessed visually and classified by location  and type . The analysis was blinded to the group assignment.t-test or the Mann–Whitney test for unpaired samples were applied to compare two groups and the one-way ANOVA test or the Kruskal–Wallis test were used to compare three groups depending on the normality of the distribution, respectively. The receiver operation curve (ROC) analysis was computed to assess the discriminating value of the analysed parameters between the DCM and athlete’s heart/controls. Parameters with the highest discriminating value were included in the multivariable logistic regression to find independent predictors of DCM. The inter-reader variability was assessed using intraclass correlation coefficients (ICCs). All tests were two-sided with the significance level set to p < 0.05. The statistical analyses were performed using MedCalc statistical software 10.0.2.0 .All results for the categorical variables are presented as a number and a percentage. Continuous variables are expressed as a mean with standard deviation (SD) or a median with an interquartile range (IQR), depending on the normality of the distribution, as assessed using the chi-squared test. Either the chi-squared test or Fisher’s exact test was used for the comparison of categorical variables, when appropriate. Student’s Subjects from all groups were of similar age. The baseline CMR characteristics were typical for each studied group .All control subjects had normal LV and RV sizes, systolic function and LV masses . Only onPeak GLS of the LV was similar in athletes and in controls, but lower in patients with DCM .A similar pattern was observed for the peak systolic GLS rate, while the peak diastolic GLS rate was similar in the athletes and in patients with DCM and lower than in the controls .The peak LV GCS and peak LV GRS were lower in athletes and in patients with DCM in comparison to the controls . A similExamples of the main LV deformation parameters as 4D reconstructions in single subjects from each group are supplied in a Differences in the peak torsion and torsion rate were observed only between the controls and patients with DCM.p = 0.028), as was the peak GLS systolic rate (p = 0.035). Besides this, no significant differences were found between the studied groups in terms of the RV deformation mechanics (The peak GLS of the RV was lower in athletes in comparison to the controls (echanics .p = 0.003).The ROC analysis included the parameters that best differentiated between the adaptive changes (athlete’s heart) and maladaptation (DCM) in the univariate analysis. It revealed that five parameters had a very high area under the curve (AUC)  that was characterised by high sensitivity (72.7% to 100%—best for the peak LV GRS diastolic rate) and specificity (88.4–100%—best for the LV ejection fraction), as demonstrated in Of note, the left and right ventricular sizes and the RV ejection fractions had only moderate accuracy in the discrimination between physiology and pathology, with low sensitivity for LV size and RV ejection fraction (50% and 59.1%) and low specificity for RV size (41.9%), as demonstrated in The inter-reader variability was analysed using 20 randomly peaked studies from the whole sample. The ICCs for the assessment of the peak LV GLS, GCS and GRS were 0.95, 0.96 and 0.98 respectively. The ICCs for the assessment of the peak torsion and RV GLS were 0.91 and 0.92.Our study was the first to analyse the differences in the deformational mechanics of both ventricles of the heart in endurance athletes, non-athletic controls and patients with DCM. Previous studies, which were performed mostly using echocardiography, compared athletes to controls ,14,15,16Sports cardiologists are occasionally faced with the need to differentiate pronounced forms of athlete’s heart—including a marked enlargement of the LV with borderline LV ejection fraction—from DCM, which, in the preclinical phase, can present in a similar form ,9,10. DiA deeper analysis of LV and RV systolic and diastolic function, including deformation parameters and rotational mechanics, may benefit the differentiation process. CMR appears to be a favourable and reproducible tool for this purpose due to its good signal-to-noise ratio, which allows for clear delineation of the heart structures and endo- and epicardial contour detection with modern postprocessing tools, as demonstrated in our study. Therefore, unlike with echocardiography, a reliable analysis does not have to be limited to GLS and can include other parameters, such as GCS, GRS or torsion, as well as RV mechanics. CMR is also one of the imaging methods that is recommended by experts for routine use in grey zone cases of athlete’s heart, as the analysis of deformation parameters comes at no additional cost and can be done in the postprocessing stage ,10. HoweWe have demonstrated that each of the analysed groups has its unique deformational characteristics for left and right ventricular cardiac muscle. It has been previously shown that elite athletes have improved LV systolic performance at rest, which is characterised by significant shortening of the systolic time duration in comparison with sedentary controls, in association with a significant increase in the LV emptying velocity . We havePathological remodelling of the heart in DCM is characterised by enlargement of the LV, which is accompanied by decreased LV systolic performance at rest. A lower LV ejection fraction in patients with DCM in comparison to AH is an effect of further decreases in peak GCS and GRS, but also of a decrease in other parameters of systolic LV performance, such as peak LV GLS and peak torsion. In our study, peak LV GCS and GRS diastolic rates seemed to best discriminate physiological from pathological LV remodelling, with peak LV GRS diastolic rate being the only independent predictor of DCM. The peak LV GRS diastolic rate and LVEF can potentially be considered as complementary discriminatory parameters in the differentiation between DCM and AH, as the first one had perfect sensitivity and the other one showed perfect specificity, as demonstrated in our study.From a pathophysiological standpoint, our results can be explained by the type of scarring present in patients with DCM, which is often diffuse and not visible with simple LGE imaging. GCS represents mid-wall fibers and GRS represents epicardial fibers, which are typically affected by the fibrosis observed in DCM, in contrast to GLS, which is more representative of subendocardial scarring that is typical for ischaemic cardiomyopathy ,28.Our study has some limitations. We included endurance athletes with enlarged heart chambers and nonathletic controls, but not athletes lacking features of AH as a comparison group . FurtherThere is a distinctive deformation pattern that is typical of each of the analysed groups, which could help in differentiating between athlete’s heart, a nonathletic heart and dilated cardiomyopathy. The peak left ventricular global circumferential and radial strains, as well as their diastolic strain rates, are parameters that are characterised by very good sensitivity and specificity when differentiating between physiology and pathology. The peak left ventricular global radial diastolic strain rate was the only independent predictor of dilated cardiomyopathy.


There was also difference in early diastolic velocity (Ea) of the septal part of the mitral annulus . The subclinical deterioration of systolic function is presented even in asymptomatic DMD female carriers.To assess subclinical cardiac function impairment in Duchenne dystrophy (DMD) female carriers. Forty-four female subjects proved as DMD carriers underwent echocardiographic examination including tissue Doppler imaging (TDI) of mitral and tricuspid annulus. Seventeen age-matched healthy female subjects served as controls. A significant differences in peak systolic annular velocity (Sa) between carriers and controls were found for lateral and septal part of the mitral annulus and for tricuspid annulus (0.09 vs. 0.11 m/s,  DMD gene are perceived healthy. Nevertheless, they have only one functional variant of the gene on one of the X chromosomes.Duchenne (DMD) and Becker (BMD) muscular dystrophies are hereditary diseases linked on X chromosome. Thus, manifestation of skeletal muscle wasting, but also cardiomyopathy occurs in males, while female carriers of the defective 1 affects primarily skeletal muscles, but also heart impairment may occur as a cardiomyopathy2. Cardiac involvement manifests as progressing decline in diastolic function, systolic ejection fraction, and fractional shortening3. Related is myocardial fibrosis, with muscle contraction impairment4.In male patients, dystrophy has prevalence of 1/3500–60005 as consequence of non-functional dystroglycan complex has number of consequences, e.g. increase oxidative stress, ion channel disturbances as well as numerous molecular pathways alteration8 eventually leading to impaired heart muscle regeneration, possibly due to stem cell depletion9 The severity of cardiomyopathy is not always in correlation with skeletal myopathy and cardiac impairment occurs long before clinical symptoms10. In female carriers, the clinical symptoms are mostly not presented, thus cardiac function has not been studied in depth. Nevertheless, in case studies were published severe heart failure episodes in different settings as peripartum cardiomyopathy, perioperative stress and others15, possibly leading even to heart transplantation16. The muscular symptoms of DMD carriers may vary from asymptomatic individuals to muscular weakness, frequent falling, difficulties in running or jumping or climbing stairs 17. Still complex prospective randomized studies are missing.There is number of proposed mechanisms of the disease etiology, primary sarcolemmal tears4 in young males with manifest Duchenne dystrophy we used cardiac magnetic resonance (CMR) to assess the cardiac function and early signs of affection of the heart by T1 mapping because echocardiography has some difficulties due to skeletal deformities and narrow intercostal spaces. Female carriers do not present rib cage anomalies, thus we used echocardiography with tissue Doppler imaging as first line method to assess subclinical cardiac dysfunction. Our another study18 with asymptomatic DMD female carriers with preserved left ventricular (LV) ejection fraction (EF) proved lower global longitudinal strain, global circumferential strain and radial strain on CMR in comparison with healthy controls. The subjects enrolled in this study had no history of weakness, falling or problems with stairs climbing or walking longer distances (more than 1 km), as well as no history of heart disease. They also had absence of cardiac symptoms like severe dyspnea, ankle swelling or palpitations. The aim of this study is to assess detectable changes of tissue Doppler parameters in asymptomatic carriers in comparison with healthy control subjects.In our previously published study19. The demographic and clinical characteristics of cohort are presented in Table Forty-four female subjects with genetically diagnosed presence of DMD allele underwent echocardiography examination on standard ultrasound device Vivid 9 . Measurements of heart dimensions, LVEF, valvular morphology and parameters and tissue Doppler imaging of mitral and tricuspid annular velocities were performed. The dimensions were measured from parasternal long axis view, EF was calculated according to Simpson’s rule. Tissue Doppler curves were obtained from standard apical four-chamber view, the peak systolic (s´), early diastolic (e´) and late diastolic (a´) velocities of lateral and septal part of the mitral annulus and lateral tricuspid annulus were obtained. The ratio between early diastolic (E) wave of transmitral flow and average of mitral annular lateral and septal velocities (E/e´) was calculatedThe study was performed in accordance with the Declaration of Helsinki (2000) of the World Medical Association, and was approved by the institutional ethics committee . Written informed consent was obtained from the subjects and/or their legally authorized representative.The female carriers of dystrophin loss-of-function mutation were statistically compared with the age-matched female controls. Because most variables were either integers or did not follow Gaussian distribution, non-parametric Mann–Whitney U-test was used for the statistical comparison. The value of α = 0.05 was set as the significance level in all tests. All analyses were performed using Statistica software .p = 0.01). No serious valvular disease was found in carriers group. The LV diastolic parameters (E/A and E/e´ ratio) were also without significant difference. However, in tissue Doppler parameters were differences in mitral e´ wave from septal part of mitral annulus, a´ wave from septal and lateral mitral annulus, and s´ wave from both parts of mitral and also tricuspid annulus. All above mentioned annular velocities were significantly lower in carriers in comparison with controls. The basic echocardiographic data are presented in Table The both groups did not differ in age, left and right ventricular end-diastolic diameter, interventricular septal, posterior wall and left atrial diameter, and ejection fraction. There was only slight difference in LV end-systolic dimension  is very sensitive marker of LV dysfunction, even in subjects with preserved ejection fraction (EF) or in diabetic patients without cardiac disease22. Reduced TDI velocities were also found in asymptomatic carriers of hypertrophic cardiomyopathy mutations without presence of cardiac hypertrophy23. The early diastolic annular velocity is one of the most powerful predictive echocardiographic parameters25. The e´ parameter is very sensitive marker of impaired diastolic function and it decreases in all stages of diastolic dysfunction19. In advanced phases of diastolic failure, the e´ velocity remains low, but the E wave velocity is high as LV filling pressure increases, so the E/e´ ratio increases as well27. Although TDI values obtained from Duchenne dystrophy carriers in our study were in normal range according to age28, significant difference particularly in systolic parameters (s´) was found in comparison with age-matched control group. Several subjects had s´ from lateral mitral annulus below 5th percentile of normal values range. On the other hand, diastolic parameters did not differ so clearly, only septal e´ and Aa and lateral a´ were substantially lower. The E/e´ ratio was normal in both groups without significant difference. The prevalence of cardiomyopathy in female DMD carriers varies in wide range and does not correlate with phenotype, muscle symptoms, creatinine kinase levels or age29. Also ECG changes, including Q-waves in the lateral leads , R- mm in V1 and R/S in V2 were described in DMD carriers 30. In our study were enrolled only asymptomatic carriers without developed cardiomyopathy, but the slight impairment of systolic LV and RV parameters is presented even with normal diastolic function. This is in concordance with previous studies31;, where impairment of systolic function was more pronounced than in diastolic echocardiographic parameters. However, this study assessed heart dimensions and fractional shortening, not tissue Doppler parameters. Also prevalence of dilated cardiomyopathy was relatively high (8.2%) in contrast with our study, which comprises asymptomatic subjects with normal ejection fraction and without significant LV dilation. So there is a premise, that DMD even at early stages affects primarily contractile function of cardiomyocytes, without influence on relaxing process and LV filling patterns. There were some limitations in our study. First, small number of patients, but on the other hand, DMD is a rare disease so it is difficult to enroll more subjects in nationwide study within the Czech Republic. The another one is absence of use of strain in echocardiography, but in the case of diffuse myocardial impairment tissue Doppler echocardiography provides sufficient information of heart dysfunction and it is easier and faster to obtain.The main result of our study was the fact that even asymptomatic DMD carriers without significant systolic dysfunction have signs of subclinical systolic function impairment. Although strain and speckle tracking has become mostly used techniques for detail assessment of cardiac function by echocardiography, tissue Doppler imaging (TDI) remains one of the most powerful and well proved method in heart dysfunction diagnosticsThe subclinical deterioration of systolic function is present even in asymptomatic DMD female carriers. Tissue Doppler echocardiography is very appropriate, fast, simple and non-invasive method to assess subclinical cardiac dysfunction in DMD carriers. Larger studies with follow-up of subjects are needed.


Significantly lower TREC values were detected in patients with 22q11.2 del and conotruncal heart defects compared to those with non-syndromic conotruncal (p < 0.001) and non-conotruncal (p < 0.001) defects. In contrast, no significant difference was found between patients with non-syndromic conotruncal and non-conotruncal heart defects (p = 0.152). Low TREC levels were obtained in neonates treated with heart surgery/intervention within 2 weeks after birth and in those with a fatal outcome (p = 0.02) independent of patient group. A correlation was found between low TREC numbers and oxygen saturation, SpO2 below 95% (p = 0.017). The SpO2 was significantly lower in the non-syndromic conotruncal group compared to non-conotruncal (p < 0.001) and 22q11.2 del group (p = 0.015). No correlation was found between low neonatal TRECs and infections needing hospitalization later in life (p = 0.135). Patients with 22q11.2 del and conotruncal defects have significantly lower TREC levels compared to patients with heart defects without this syndrome.In the fetus, the cardiac neural crest gives rise to both the thymus and the conotruncus of the heart. In newborn screening for severe T-cell lymphopenia neonates with congenital heart defects may be detected. In this study, we investigated the occurrence of T-cell lymphopenia in neonates with or without 22q11.2 deletion syndrome (del) suffering from heart defects. This retrospective cohort study included 125 patients with heart defects. T-cell receptor excision circles (TRECs), a measure for T-cell lymphopenia, were quantified by RT-PCR using stored newborn screening blood spots. Three patient groups were compared: non-conotruncal defects ( T-cell lymphopenia in neonates with congenital heart defects occurring as part of a syndrome or as a non-syndromic condition, has been described in a number of studies , 2. NewbThe incidence of congenital heart defects is approximately 1 in 100 . Conotrun = 42), non-conotruncal (n = 57), or 22q11.2 del with conotruncal heart defects (n = 26). The 22q11.2 deletion was diagnosed by fluorescent in situ hybridization , multiplex ligation-dependent probe amplification , or comparative genomic hybridization array .The patients invited to the study were identified through a registry of heart defects at the Oslo University Hospital. Our hospital has a national service for children with congenital heart defects which includes preoperative assessment and definitive treatment. Invitation letters were sent to 230 parents of children with heart defects, and 140 (61%) consented to participate. The rest did not respond to the invitation. One patient with Noonan’s syndrome and one with Turner’s syndrome were excluded from the study. In two patients, no screening card was available. In the non-syndromic conotruncal heart defect group, only patients with a negative genetic test for 22q11.2 del were included. We finally studied 125 patients born after 2005. They were diagnosed with non-syndromic conotruncal .2 values before operation/intervention, measured by pulse oximetry, were also retrieved.Patient medical records were obtained from the hospitals, and a review was conducted by the first author. Data were collected, including the type of cardiac defects, treatment procedure (surgery/ intervention), gestational age, delivery mode, the identification of a syndrome diagnosis, and information about hospitalization due to infection later in life. SpOWe used TREC levels as marker for T-cell lymphopenia , 9. TRECDNA extraction was performed in a 96-well format. One 3.2 mm dried blood spot of each patient’s screening card was punched into a 96-well PCR plate (VWR) using a Panthera puncher (PerkinElmer). 150 µL Generation DNA elution solution (Qiagen) was added to each well, and the samples were incubated at 60 °C for 10 min on a microplate shaker (Eppendorf) at 1000 rpm. The supernatant was discarded, and the DNA was extracted in 100 µL Generation DNA elution solution by incubation at 100 °C for 30 min in a PCR instrument.TREC and β-actin qPCR reactions were run in final volumes of 20 μL containing 10 µL PerfeCTa qPCR ToughMix (Quantabio), 500 nmol/L forward and reverse primers, 150 nmol/L probe, 0.4 mg/mL BSA and 8 µL DNA (4 µL for the β-actin assay). The primer sequences are provided in Table R2 values > 0.99. β-actin was used as a housekeeping gene to assure an adequate DNA extraction for PCR. Quality control was performed using TREC NBS QC provided by Center of Disease Control. The TREC value per μL was calculated assuming that a 3.2 mm punch contains ∼3 μL of blood.Copy numbers were calculated based on standard curves generated from serially diluted plasmids kindly provided by Douek . All the2 values below 95% in patients with non-syndromic conotruncal, non-conotruncal, and 22q11.2 del with conotruncal defects. The correlation between TREC groups (TREC quartiles) and heart surgery/intervention within 2 weeks of life or death was done by using crosstabs and Chi-square Linear by linear association. For other clinical comparisons, student T test was employed. A significance level of 5% was used. All figures were created using Graphpad prism.One-way ANOVA was performed with post hoc Tukey test to compare TREC values or SpOn = 57), conotruncal (n = 42), and 22q11.2 del with conotruncal heart defects (n = 26). The number of patients and the specified diagnoses are listed in Table p < 0.001) was found in the 22q11.2 del group compared to both non-syndromic conotruncal and to non-conotruncal heart defect groups. In the non-syndromic patients, a slight trend of lower TREC values was observed in the conotruncal group compared to non-conotruncal although not significant (p = 0.152). Lower TRECs were found in the 22q11.2 del group compared to the non-syndromic conotruncal group when investigating specific diagnoses such as TOF (p < 0.001), PA (p = 0.017), and IAA (p = 0.066).The patients were divided in three groups, those with non-conotruncal . A similar, but not so strong correlation was found if 22q11.2 del patients were excluded from the calculation (p = 0.041).In line with our previous study , the ris2 values preferably the first measurement after birth and obtained before heart surgery/intervention. A correlation was found between low TREC and SpO2 below 95% (p = 0.017). The SpO2 was significantly lower in the conotruncal non-syndromic group (p < 0.001) and 22q11.2 del group (p = 0.002) compared to non-conotruncal heart defects group. In the conotruncal non-syndromic group, the SpO2 was significantly lower (p = 0.015) than in 22q11.2 del.In 101 patients, we were able to collect neonatal SpOn = 6), conotruncal (n = 1) or 22q11.2 del with conotruncal (n = 5) heart defect, respectively. Exclusion of these patients gave similar TREC results (data not shown). Also, no association was found between TRECs and birth weight  or delivery mode .Twelve of the patients were premature Table , born inn = 103) was found between the newborn TREC value and serious infections occurring later in life. The number of patients hospitalized due to infections is presented in Table No association n = 10 was founWe found significantly lower number of TRECs in 22q11.2 del patients with conotruncal heart defects compared to patients with conotruncal and non-conotruncal defects without this syndrome. Non-syndromic patients with conotruncal defects had a tendency, although not significant, of lower TREC values than those with non-conotruncal defects. In line with our results Sullivan et al.  found lon = 353) with 22q11.2 del. They found no correlation between T-cell numbers and the severity of cardiac anomaly  or the complexity of the surgical procedure.We also compared the TREC values in neonates with and without the syndrome, suffering from different groups of conotruncal heart defects . We found significantly lower TREC values in TOF and PA patients with 22q11.2 del. Sullivan et al.  studied In this respect the common embryology of the heart and the thymus is interesting. The thymus develops from the 3rd pharyngeal pouch endoderm and cardiac neural crest cells , 17. TheDar et al.  compared2 is below 95%. However, the SpO2 was significantly lower in non-syndromic conotruncal heart defects compared to patients with 22q11.2 del. This suggests that stress alone cannot explain the low TRECs in 22q11.2 del group, and a study of 29 infants with chronic hypoxia due to cyanotic congenital heart disease, did not show any effect on the HPA axis [In animal models, cyanotic heart disease causing hypoxia has been found to increase endogenous glucocorticoid production –28. ThisHPA axis . GerstelHPA axis  demonstrHPA axis  describeHPA axis . A bettePrevious studies have shown a correlation between prematurity and low TREC levels , 33. TREIn 103 patients, we had information about later hospitalizations. As in our previous report , we did In the present study we have demonstrated that neonates with 22q11.2 del and conotruncal heart defects have significantly lower TREC levels than non-syndromic patients with conotruncal or non-conotruncal defects. This result indicates that T-cell lymphopenia  observed in the conotruncal heart defects is mainly due to the chromosome 22q11.2 deletion. However, the stress due to the conotruncal heart defects in either group may also affect thymus function and result in low TREC values.


BackgroundResuscitation guidelines recommend that chest compressions be performed over the lower sternum. Current computed tomography and magnetic resonance imaging studies suggest that the current area of compression does not target the left ventricle (LV). Using transthoracic ultrasound, we sought to identify potential anatomic landmarks that would result in compressions over the LV in the majority of our study participants.MethodologyWe recruited 64 healthy men and women (over the age of 40) from the Simulated Patient Program at the University of Saskatchewan. Using ultrasound, we identified the LV and the associated surface anatomy in terms of intercostal space (ICS) and parasternal or mid-clavicular lines. We also collected biometric data including body mass index, chest circumference, and the corresponding inter-nipple line ICS.ResultsThe LV was located along the left sternal border in 62 (96.9%) participants. The most frequent LV location was along the left sternal border at the sixth ICS in 26 (40.6%) participants, with 13 (20.3%) at the fifth and 10 (15.6%) participants at the seventh ICS. In two (3.1%) participants, the LV was found along the mid-clavicular zone at the fifth ICS. The area from the fifth to seventh ICS on the left sternal border, typically covered by an adult palm centered at the sixth ICS, overlaid 49 of 64  identified LV locations. By comparison, centering the heel of the palm over the inter-nipple line at the left sternal border would cover the LV in 46  participants. ConclusionsA novel area of compression over the left sternal border at the inter-nipple line would result in compressions over the LV in nearly three-quarters of our study participants. Future research should investigate whether this proposed area of compression is applicable to a broader population including those with cardiac and thoracic disease. Despite automated defibrillation and compression-focused resuscitation, out-of-hospital-cardiac-arrest survival remains 10% . A mainsA porcine study  demonstrWhile TTE and TEE can be used to identify the LV and guide compressions, this is not currently a practical solution for out-of-hospital cardiac arrest. Using ultrasound, we sought to localize the LV and then correlate its location to external anatomic landmarks, thus identifying a novel area of compression that would overlie the LV in the majority of our study participants.2 (m) and classified as normal (<25), overweight (25-29.9), or obese (≥30).We obtained approval from the University of Saskatchewan’s Research Ethics Board (Bio #461) to conduct a pair of investigations exploring rapid localization of the LV through either sonographic  or anatoParticipants were placed in a supine position and ultrasound localization of the LV was performed by authors PO and RW using GE Venue 40 machines . The ultrasound transducer was oriented along known echocardiographic windows including the parasternal long axis, apical four-chamber, and subcostal views. If a parasternal view of the heart was successfully obtained at the location, the space was deemed to be overlying either the long axis of the LV or aortic root (depending on which was the dominant structure in the view). If an apical four-chamber view was obtained, the space was deemed to be overlying the apex. If a subcostal view was obtained, the space was deemed to be overlying the inferior border of the heart . Location of this position was plotted on a grid consisting of ICSs three to seven and two longitudinal zones: the left sternal border and mid-clavicular zones . Ultrasound was also used to describe the participant’s thorax including a scan for both pleural and pericardial effusions.In clinical echocardiography, the LV is usually along the left sternal border between the third to fifth ICSs with the patient in left lateral decubitus ,21. ThesThe most common means of compression in cardiac arrest is the heel of the human palm, measuring a mean width of 7-8 cm in females and 8-9 cm in males ,24. The Descriptive statistics  were calculated to characterize the demographic and anatomical features of participants. ICSs of the inter-nipple line and LV location were cross-tabulated to assess consistency; proportions agreeing and their 95% confidence intervals (CIs) were determined. To account for the heel of the hand, agreement between anatomical landmarks and LV location was also assessed allowing for a margin of one ICS above and below the anatomical location. Agreement was assessed for the sample as a whole and by subgroups of sex and BMI. Exact CIs were determined for sex-specific and BMI category-specific proportions due to the relatively small number of participants in the subcategories. Proportions were compared between subgroups using the chi-square test. IBM SPSS Statistics for Windows, version 27  was used for analysis.Demographic and anatomical details for participants are outlined in Table The ICS of the inter-nipple line and LV were consistent among 21  participants, all with the LV at the left sternal border. The region at the left sternal border covering one ICS above the inter-nipple line to one ICS below it overlaid the LV in 46  participants. The degree of agreement between the level of the inter-nipple line and the LV are presented in Table Localization of the LV location by anatomic landmarks is described in Table Our findings demonstrate that the LV is found to the left of the sternal border in a majority of supine adult participants. An area of compression over the left sternal border at either the sixth ICS or the inter-nipple line would result in compressions over the LV in the majority of our study participants. We report both of these anatomic locations because, despite evidence of improved LV localization at the sixth ICS, palpation of ICSs is challenging and has been found for chest tube insertion . In contMultiple radiological studies evaluating the location of critical cardiac structures have been published. In computed tomography (CT) and magnetic resonance imaging (MRI) studies, it has been demonstrated that the lower half of the sternum mostly compresses structures other than the LV including the ascending aorta, left atrium, right ventricle, aortic root, and proximal descending aorta ,7-9.2, but no improvement in survival. This may be attributed to the duration of standard compressions prior to LV localization and subsequent targeted LV compression [A case series of five patients with TTE-guided LV compressions showed promising improvements in oxygen saturation and end-tidal COpression . The autpression ,10,21.Our study has several limitations. First, while we propose a novel area of compression overlying the LV, we present no data on the actual effects such a move would have on human patients during cardiac arrest in terms of hemodynamics, trauma to internal organs, survival, or other clinical outcomes. Our sample size was relatively small, and even though we did not screen our participants, the majority were generally healthy. Patients who suffer cardiac arrest likely have a higher prevalence of cardiac and thoracic pathology, most importantly cardiac dilation, which may result in lateral displacement of the LV and its axis. We used ultrasound to localize the heart as opposed to CT or MRI, and we did not perform blinded comparisons of location to ensure inter-rater reliability. While cardiac ultrasound is a user-dependent skill, both authors performing the scans have completed training in focused cardiac ultrasound consistent with the guidelines set forth by the Canadian Association of Emergency Physicians .Utilizing ultrasound to map the position of the LV to the surface anatomy of our adult participants, we were able to identify an area of compression that may result in LV compression in most patients. Performing chest compressions over the left sternal border at the intersection of the inter-nipple line should be feasible for first responders and could optimize chest compression in cardiac arrest in a majority of patients. Further investigation is warranted to determine if the proposed area of LV compression is valid in a larger cohort of patients including those with cardiac and thoracic disease.


In patients with moderate/severe FMR, MA diameters correlated with PISA radius, EROA, and regurgitant volume (Rvol), as also did the MA area . MAFAC correlated inversely with EROA and Rvol , with both active and total LA emptying fractions and with LV ejection fraction as well. In a stepwise multivariate regression model, decreased MAFAC and increased LA volume independently predicted patients with severe FMR.  Patients with FMR vs. controls presented increased MA size and sphericity during the entire systole, whereas MA fractional area change (MAFAC) and MA displacement were decreased (15 ± 5 vs. 28 ± 5%; and 5 ± 3 vs. 10 ± 2 mm,  Patients with DCM and FMR have MA geometry remodeling and contractile dysfunction, correlated with the severity of FMR. MA contractile dysfunction correlated with both LA and left LV pumps dysfunctions and predicted patients with severe FMR. Our results provide new insights that might help with better selection of patients for MV transcatheter procedures. Functional mitral regurgitation (FMR) is a common complication in patients with ischemic or nonischemic dilated cardiomyopathy (DCM), increasing mortality, and the risk of rehospitalization . In patiRecent studies suggested an association between the anteroposterior diameter of the mitral annulus (MA) and FMR recurrence after MV interventional treatment . HoweverAccordingly, we designed our study (i) to characterize MA geometry and dynamics changes, as the remodeling of the MA, by using 3DTTE in patients with DCM and FMR, in comparison with healthy controls; (ii) to assess the relationship between MA remodeling and severity of FMR; and (iii) to assess the relationship between MA dysfunction and severity of LV and LA dilation and dysfunction.We conducted a prospective study, in which we enrolled 56 patients with mild-to-severe FMR due to ischemic and nonischemic DCM and compared them with 52 control subjects, similar in age, gender, and BSA. All subjects were in sinus rhythm and had complete 3DTTE datasets for MV, LA, and LV. Patients with more than mild aortic, pulmonic, or tricuspid valve disease, significant MV calcifications, or poor-quality image of the 3DE datasets were excluded. Control subjects were healthy volunteers free of any cardiovascular history or risk factors. Heart rate, blood pressure, height, and weight were measured in all subjects immediately before the echocardiographic examination. Body surface area (BSA) was calculated . EtiologEchocardiography was performed in accordance with a standardized acquisition protocol, with a Vivid E9 system , equipped with M5S and 4V probes. Standard transthoracic echocardiography was performed to assess LV size and function and etiology and severity of FMR in patients with DCM. Then, to obtain high temporal resolution of the datasets, separate 3D full-volume multibeat acquisitions of the MV, LV, and LA were obtained by combining six consecutive ECG-triggered subvolumes, during breath-hold and avoidance of patient or probe movement. Care was taken to encompass the MV in the full volume throughout the cardiac cycle and the entire LV and LA in the dedicated dataset. By using multislice display, the absence of stitching artifacts in the acquired dataset was carefully checked.The severity of FMR was graded as trivial/mild, moderate, and severe, using two-dimensional (2D) echocardiography, according to the current guidelines . QualitaLV 3DTTE datasets were stored digitally in raw-data format for offline analysis , as previously described and validated against cardiac magnetic resonance (CMR) , 15 Fig.LA 3DTTE datasets were converted to DICOM format and analyzed using dedicated software package designed for volumetric analysis of the LA and recently validated against CMR  . At the static analysis) and then during the cardiac systole  , as previously described . Brieflynalysis) . MA meast-test. Pearson's correlation was used to analyze the relationships between MR severity parameters and MA function and between MA function and LA and LV parameters. Multiple linear backward regression tests were used to identify the parameters that independently correlated with severe MR. All analyses were performed using SPSS version 20.0  and MedCalc version 10.0.1.0 . Differences among variables were considered significant at p < 0.05. Our group has previously reported the reproducibility for the echocardiographic methods, in unselected patients with MV disease [Normal distribution of variables was checked by Kolmogorov–Smirnov test. Continuous variables were summarized as mean ± SD, and categorical variables were reported as percentage. Variables were compared between groups using unpaired  disease .2 and RVol 26 ± 19 ml, available in 33 patients (59%). Temporal resolution of the 3D datasets for MA analysis was 32 ± 7 volume/sec in patients with FMR and 35 ± 6 volume/sec in control subjects (p=0.87). The number of systolic frames in each dataset ranged from 9 to 17, depending on heart rate or acquisition settings. Static analysis of the MA was feasible in all subjects. Dynamic analysis of MA was feasible in 54 patients with FMR (96%) and in 48 control subjects (92%).The general characteristics of the study population are summarized in Mitral annulus static analysis is shown in Comparisons between LV, LA, and MA parameters in patients with trivial/mild, moderate, and severe FMR are shown in r = 0.56 and r = 0.43; with EROA: r = 0.66 and r = 0.45; and with RVol: r = 0.53 and r = 0.39, all p < 0.05), as did also MA area . MV tenting volume correlated with PISArad  and with Rvol , while MV tenting correlated only with PISArad . MA fractional area change correlated inversely with EROA and Rvol .In patients with moderate and severe FMR, MA diameters (AP and ALPM) correlated with all quantitative parameters of FMR severity (with PISArad: p=0.03), AP diameter fractional change (p=0.02), and MA fractional area change (p=0.003), respectively.In a multiple backward linear regression model using indexed LVEDV; LAVmax; MA area; LVEF; active and total LAEFs; AP diameter fractional change; and MA fractional area change, independent predictors for severe MR were the LAVmax . MA area fractional change correlated with both active and total LAEFs, as well as with LVEF, while MA AP diameter fractional change showed similar behavior; MA displacement correlated only with LVEF  increased MA size and sphericity, during the entire cardiac systole, was associated with a concomitant remodeling of the MV leaflets; (ii) MA was flatter, with increased MV tenting height, area, and volume during the cardiac systole; (iii) maximum MA contraction was not only decreased in amplitude, but also delayed in time; (iv) MA size and contractile dysfunction correlated with FMR severity; and (v) MA contractile dysfunction correlated with both LA and LV dysfunctions.MA remodeling and dysfunction have been reported as mechanisms of both ischemic and nonischemic FMR , 20, 21.Patients with mild-to-severe FMR showed MA dilation throughout the entire systole, as previously reported , 21. HowMA was flatter in patients with FMR than in control subjects. Similar with the data reported by Topilsky et al. , our patBeside MA enlargement and remodeling, patients with FMR also showed altered relation of the MA with the surrounding structures, presenting wider Ao-AP angle than control subjects. This has to be taken into account for annuloplasty techniques, as the angle Ao-AP proved to predict the occurrence of systolic anterior movement of the anterior mitral leaflet after MV annuloplasty . MoreoveLV dyssynchrony has been reported as a mechanism of FMR, while cardiac resynchronization therapy (CRT) can reduce early systolic FMR in selected patients –31, but MA area fractional change was increasingly impaired in patients with FMR. We showed that the “contractile dysfunction” of the MA was associated with both LA and LV dysfunctions. In patients with DCM, Kwan et al.  reportedOtsuji et al.  showed tIn our study, we did not assess the complex relationship between papillary muscle position, orientation, and FMR severity; however, this has been extensively assessed in previous studies –40. The Patients with dilated cardiomyopathy and functional mitral regurgitation have mitral annulus geometry remodeling and contractile dysfunction, which correlated with the severity of mitral regurgitation. Mitral annular contractile dysfunction correlated with both left atrial and left ventricular pump dysfunctions. Thus, these results enhance the association of atrial remodeling and dysfunction with the severity of functional mitral regurgitation severity, mediated through the mitral annular dysfunction. Our results may ensure further studies to use parameters of the mitral annular size and geometry, in order to help us to better select patients for transcatheter procedures, targeting the mitral annulus or the mitral valve.


As the outcome of patients with congenital heart disease (CHD) has improved, the number of adults with congenital heart disease (ACHD) outnumbered pediatric population with CHD. Heart failure is responsible for 40% of mortality among ACHD, and the number of heart transplantation for ACHD is gradually increasing. However, the early mortality rate of heart transplantation is significantly higher in ACHD than in non-ACHD. Understanding the unique characteristics of heart transplantation in ACHD is critical. In contrast to their early outcome their long-term survival is better in ACHD than in non-CHD patients, and they are likely to present to anesthesia care after heart transplantation for various reasons. Understanding specific issues in post-transplant anesthesia care is another important aspect. Congenital heart disease (CHD) is the most common anomaly with an incidence of 4–8/1,000 live births . In 2010The heterogenous nature of ACHD complicates the universal application of typical heart failure therapies . AccordiHistorically most ACHD have received low-priority on the heart transplant waiting list. As a result, ACHD tends to be on the waiting list for a much longer time than non-CHD patients, and these patients often seek medical care during this period. Thus, it is possible that these patients present to any local hospital for care at any stage of their heart failure. These transplantations have been performed widely not only in non-Adult Congenital Heart Association accredited centers but also in non-accredited centers . These pACHD patients who present for heart transplantation may be receiving a number of heart failure therapies including pharmacological intervention and synchronization therapy. Some may have MCS in place. Heart transplantation surgery consists of the pre-cardiopulmonary bypass (CPB) phase, the CPB phase where explantation of the native heart and/or MCS device and implantation of donor heart is performed, and the post CPB phase.The anesthetic management during this phase is largely dependent on the underlying diseases and conditions. In general, ACHD with advanced heart failure can be classified into 1) Patients with uncorrected defects, 2) Patients who underwent repair or palliation but developed heart failure, and 3) Patients with failing single ventricle physiology. Unfortunately, both national and international databases lack information on the underlying defects and prior palliative procedures of ACHD undergoing heart transplantation. According to case series, 40–50% of patients have single ventricle physiology with failing Fontan circulation ,8. SurgiFontan surgery underwent several modifications since its initial report in 1971 . CurrentSurgically corrected transplantation of the great arteries is seen in patients with dextro-transposition of the great arteries (d-TGA) who underwent atrial switch operation with Mustard or Senning. Atrial switch surgery was applied to patients with d-TGA before the era when arterial switch operation was established as the standard surgical procedure for the majority of these patients. Patients who underwent atrial switch operation have morphological right ventricle as the systemic ventricle, which might present with ventricular failure. In addition to systemic ventricular failure, any complications including any obstruction of atrial baffle with clot or anatomical narrowing need to be delineated prior to planned transplantation. Congenitally corrected TGA (l-TGA) also has morphological right ventricle as the systemic ventricle. Now these patients may undergo double switch operation consisting of atrial switch and arterial switch so that they have morphological left ventricle as a systemic ventricle. However, these patients often live life without any corrective procedures.In addition, patients with MCS can present for heart transplantation. HeartMate II left ventricular assist device (LVAD) was first approved as LVAD for bridge to transplantation. HeartMate III LVAD and HeartWare HVAD are often used now. Thus, anesthesiologists who take care of them need to be familiar with the care of ventricular assist devices. It is important to know the physiology of each device. When only systemic ventricle is supported with the device, it is important to support the pulmonary ventricle or the pulmonary side of the circulation, which includes use of inhaled nitric oxide (NO) and intravenous milrinone therapy. We have previously reviewed anesthesia care for patients on MCS. Please refer to our previous publication for further detail .As above, a number of ACHD who present to heart transplantation have had previous surgical interventions. It is critical to have good vascular access to be amendable for volume resuscitation in case significant bleeding is encountered. Often these patients have had a number of interventions done through the femoral arteries and veins for cardiac catheterizations and other procedures. Patency of these vessels for femoral access is an important piece of information to gather for potential femoral cannulation when difficult sternotomy is anticipated. If they are not available, alternative plan for cannulation for CPB should be well discussed with the surgical team.A number of ACHD patients have prior surgical interventions. Furthermore, the presence of aortopulmonary collaterals can often impede surgical field visibility. Dissection and explantation of heart and/or device can be difficult. Implantation usually consists of connecting SVC and IVC and left atrium cuff to the donor heart. However, reconstruction of vascular structures may be required. The procurement surgeon often has to obtain extended donor veins and aorta for this purpose. These complicated surgical issues may contribute to longer ischemic time. In the study by Karamlou, et al., the average ischemic time was 3.8 hours in the ACHD arm, while it was 2.9 hours in the non-ACHD arm .As a part of the heart transplantation workup, the assessment of pulmonary vascular resistance (PVR) is mandatory. However, the measurement may not be accurate in ACHD due to 1) Presence of multiple sources of pulmonary blood supply due to the presence of aortopulmonary collaterals or shunt and 2) Low pulmonary blood flow . In the Early postoperative mortality is higher for ACHD patients. In a systematic meta-analysis, the 30-day mortality was 17.4% in ACHD, while it was 7.4% in non-ACHD [Given that the long-term outcome of ACHD heart transplant recipient is better than non-CHD patients, it is easily expected that they could present for a variety of procedures requiring anesthesia care. Some of the procedures may be able to be done with sedation. ACHD often have extensive experience with previous hospitalizations and procedures. However, these experiences may not make sedation for seemingly simple procedures amendable for this patient population due to their anxiety. General anesthesia may be indicated in a number of cases.A number of reviews and case reports have discussed the anesthetic considerations in heart transplant recipients for further review –17. CardACHD patients with heart failure increasingly undergo heart transplantation. They pose a significant challenge to anesthesiologists during heart transplantation and after transplantation, and understanding their pathophysiology would be critical for the further improvement of their outcomes.


Subclinical diabetic cardiomyopathy (DCM) occurs frequently in asymptomatic subjects with Type 2 diabetes mellitus (T2DM). The direct association between the immune system and DCM with effective biomarkers has been demonstrated in previous studies.Five hundred seven subjects with T2DM were recruited from April 2018 to October 2019 and divided into T2DM with cardiac dysfunction (DCM) group and T2DM without cardiac dysfunction (non-DCM) group. The relationship between the quartiles of Neutrophil: lymphocyte ratio (NLR) and subclinical DCM was evaluated by using adjusted logistic regression models..P = 0.05). Then the adjusted odds ratio (95% CI) of the highest NLR quartile was 14.32 (2.92–70.31) compared with the lowest quartile of NLR after multiple adjusted (P < 0.001). However, there was no significant relation between neutrophil and lymphocyte counts and the occurrence of DCM in T2DM patients.Blood NLR was significantly upregulated in DCM group compared to non-DCM group . Registered 30 October 2019. Retrospectively registered: www.medresman.orgChinese Clinical Trial Registry  Diabetic cardiomyopathy (DCM) is defined as a heart muscle-specific dysfunction arising independently of hypertension, coronary artery disease (CAD), or evidence of other structural cardiac diseases . Recent Important pathological processes involved in DCM include cardiac hypertrophy, myocardial and interstitial fibrosis, oxidative stress, apoptosis, and microangiopathy , 9. ActiNeutrophil: lymphocyte ratio (NLR) has been recently identified as a novel biomarker of numerous inflammatory diseases –23. BecaThis research was conducted as a cross-sectional, hospital-based study. A total of 532 subjects with T2DM were consecutively recruited from the Department of Endocrinology at the Third Affiliated Hospital of Soochow University  from April 2018 to October 2019, based on a priori protocol that was independent of the indications found with the echocardiographic examination. Of the 532 subjects with T2DM, 25 were excluded after gated-myocardial perfusion imaging  suggested the presence of occult CAD. All protocols were carried out in accordance with the principles outlined in the Declaration of Helsinki and the study was approved by the institutional review committee of the Third Affiliated Hospital of Soochow University. The ethics Committee of the Third Affiliated Hospital of Soochow University approved the study, which has been registered in the Chinese Clinical Trial Registry (ChiCTR1900027080).The inclusion criteria for the subjects were: T2DM patients aged from 40 to 70 years, without regard to the duration of diabetes. The clinical treatment was composed of the oral use of anti-diabetic drugs and/or insulin injection. We excluded participants with one or more of the following characteristics: 1. A history of CAD, hypertension, valvular heart disease, atrial fibrillation, or any other cardiovascular disease. 2. A self-reported history of symptomatic macrovascular or microvascular complications of diabetes, including retinopathy, nephropathy, neuropathy, peripheral vascular disease, and stroke. 3. Pregnancy. 4. Other important comorbidities including infectious diseases, malignancy, thyroid dysfunction, hepatic and renal dysfunction, immune and rheumatic diseases, or significant psychiatric illness. All subjects signed informed consent prior to participating in the study.On the same day of admission to the hospital , patients with T2DM provided a complete medical history and were subjected to comprehensive physical and clinical examinations. On the following morning after admission and when the fasting time was greater than 8 h, we collected the patient’s peripheral blood samples. All patients underwent electrocardiography (ECG), echocardiography, and gated-myocardial perfusion imaging . Eligible subjects with evidence of left ventricular diastolic dysfunction (LVDD) and no apparent occult CAD were defined as having subclinical DCM. We classified LVDD according to recommendations of the American Society of Echocardiography and the European Association of Cardiovascular Imaging . All patDemographic data were analyzed regarding the patients’ sex, age, basic anthropometry (including body–mass index [BMI] and waist-to-hip circumference ratio), duration of diabetes and concomitant hypoglycemic drug use. The clinical data obtained included the levels of B-type natriuretic peptide  and myocardial enzymes. Biochemical analysis was performed to determine the levels of alanine aminotransferase (AST), glutamic oxaloacetic transaminase (ALT), creatinine, urea nitrogen (BUN), and creatinine (Cr). Metabolic measurements included fasting-blood glucose (FBG), postprandial-blood glucose (PBG), HbA1c, and lipid profiles. Briefly, HbA1c was measured with boronate affinity high-performance liquid chromatography. HbA1c values were corrected on the basis of the correlation coefficient that was derived from a validation experiment that used sample data that were measured on both analysers. Serum Cr, BUN, myocardial enzymes, BNP, ALT, AST, and lipid profiles including triglyceride, total cholesterol, HDL-cholesterol, LDL-cholesterol were measured on a Modular P800 anayser . The clinical and metabolic data were measured after fasting for at least 8 h and before administering hypoglycemic agents.The following echocardiography parameters were determined: the left atrial diameter (LAD), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), interventricular septal diameter (IVSD), left ventricular ejection fraction (LVEF), left atrial mass (LA mass), LA mass index, peak early diastolic trans-mitral flow velocity (E), peak late diastolic trans-mitral flow velocity (A), and peak early diastolic mitral annular velocity (e′). The E/A ratio, E/e′ ratio, and LA volume indexes were calculated to evaluate the diastolic function.99mTC-MIBI MPI was performed for each subject based on a 2-day standard imaging protocol  in blood samples of subjects with T2DM. At present, it is not clear which mechanism(s) can explain the association between diastolic abnormalities and NLR. Therefore, the relationship between LVDD and activation of the immunoinflammatory system should be studied more thoroughly in the future, both on experimental and clinical grounds.Additional file 1 : Supplemental Table 1. Participant characteristics of T2DM with or without cardiac dysfunction. Supplemental Table 2. Echocardiographic features of participants with or without cardiac dysfunction. Supplemental Table 3. ROC analysis for continuous predictor.


To assess the atrial and ventricular diastolic function response to dobutamine stress in Fontan patients, and to relate these measurements to exercise capacity and events during the follow-up.We performed a secondary analysis of a cross-sectional multicentre study of Fontan patients with intra-atrial lateral tunnel (ILT) or extracardiac conduit (ECC) modification. Subjects underwent cardiac MRI during rest and low-dose dobutamine stress, and cardiopulmonary exercise testing. Atrial and diastolic ventricular function parameters were derived from volume-time curves.Medical records were abstracted for a composite end-point of death, listing for transplant, arrhythmia and reintervention. Spearman’s r correlation tests and Cox proportional hazards models were used to assess the relation between the dobutamine response for atrial and diastolic ventricular function and outcomes, including exercise capacity.2, p<0.001), as did early (1.9 (−1.6 to 3.6) mL/m2, p=0.001) and late emptying volume (2.2 (0.2–4.4) mL/m2, p<0.001).We included 57 patients  aged 12.8 (IQR (10.3–15.5)) years. During dobutamine stress atrial cyclic volume change increased (3.0 (0.4–5.9) mL/m2, p=0.046) and ventricular late filling increased (1.0 (−0.4 to 3.4) mL/m2, p<0.001) while stroke volume remained similar.Ventricular early filling decreased (−1.6 (−5.7 to 0.7) mL/mOnly for patients with the ECC modification, atrial early emptying volume increase correlated with peak oxygen uptake . No other parameter related to exercise capacity.During a median 7.1-year follow-up, 22 patients reached the composite endpoint. No parameter predicted events during the follow-up.Dobutamine stress augmented atrial reservoir and pump function for Fontan patients. Atrial early emptying reserve related to exercise capacity in ECC patients. No other atrial or diastolic ventricular function parameter related to outcomes. Fontan patients are generally limited by impaired single ventricular inflow, but the role of the atria in ventricular filling has received little attention.Atrial reservoir and pump function increase with dobutamine stress. Higher atrial early emptying volume reserve relates to higher exercise capacity in extracardiac conduit patients.Stress testing of the pulmonary venous atrium might demonstrate occult dysfunction in Fontan patients.The Fontan strategy is the preferred treatment for univentricular heart defects.1Previously we demonstrated that atrial and ventricular diastolic function at rest—measured by cardiac MRI (CMR)—are not related to outcomes in Fontan patients.We performed a secondary analysis of a Dutch multicentre cross-sectional study.All patients underwent steady state free precession (SSFP) CMR on a 1.5T whole-body scanner. Images were obtained in either the short axis or axial orientation including complete imaging of the atria. An extended CMR protocol has been published previously.et al formula.13Segmentation was performed on a Windows workstation using Medis Suite 3.2 . Epicardial contours of the single ventricle were manually segmented in all phases and slices. All ventricular structures that eject in the aorta were segmented as a functional single ventricle. Endocardial segmentation of the ventricle was performed automatically by a threshold-based method  and manually adjusted where needed. All atrial structures that drain pulmonary venous return and unload in the single ventricle were manually segmented, considering them as a functional mono-atrium. Examples of segmentation are provided in 10.1136/openhrt-2020-001487.supp1Supplementary video10.1136/openhrt-2020-001487.supp2Supplementary videoExercise capacity and events during the follow-up were assessed. All subjects underwent cardiopulmonary exercise testing on the same day as CMR examination, as previously described.Patient records were abstracted for events during the follow-up. The day of study visit was considered day 0 for follow-up. Events were assessed as a composite endpoint, consisting of: death; listing for heart transplant; arrhythmia (defined as any arrhythmia requiring medication or intervention); and reintervention .2 test or Fisher’s exact test for tests including counts of zero. Correlations were assessed by the non-parametric Spearman’s ρ. Events during follow-up were assessed by Cox proportional hazards models. A p<0.05 was considered statistically significant. All statistical tests with regard to outcome were adjusted for multiple testing using the Benjamini-Hochberg procedure. All analyses were performed using R V.3.6.1 .Continuous data are presented as median (IQR). Continuous data were compared using the non-parametric Wilcoxon test. Paired tests were used for the comparison of rest and stress measurements. Categorical data are presented as count (percentage) and compared using the χWe identified 57 unique patients with complete examinations. Patient characteristics are shown in Thirty-nine patients had a dominant left ventricle (LV), 17 had a dominant right ventricle (RV) and 1 patient had a single ventricle of undetermined morphology. Patients with an LV and RV had similar age (13.2 (10.5–15.6) for LV vs 12.8 (10.3–15.5) for RV, p=0.737) and body surface area (BSA) (p=0.215).Moderate-to-severe AV regurgitation was present in 17 (30%) of patients. The presence of AV regurgitation did not differ between surgical modifications (p=0.882).Exercise capacity in the study population was relatively well preserved. Maximal exercise effort (RER ≥1.05) was achieved in 37 patients. For these patients peak oxygen uptake was 82% (66 – 94) of the predicted value for age.2 during dobutamine stress (p<0.001). Atrial early emptying volume increased by 1.9  mL/m2 (p<0.001). Conduit volume did not change during dobutamine stress (p=0.092). For ECC patients atrial maximal volume decreased during dobutamine stress (difference −3.3 (−11 to 1.5) mL/m2), whereas ILT patients increased maximal volume by 2.7 (−0.6 to 6.9) mL/m2 (p=0.001 for difference between ILT and ECC). Similarly, atrial conduit volume increased for ECC patients during dobutamine stress and decreased for ILT (2.7 (−2.7 to 6.5) vs −4.7 (−9.2 to −0.5) mL/m2 change, p=0.003).Atrial cyclic volume change increased from 9.7 (7.5–12.7) to 13.5 (10.1–17.0) mL/mNo parameter of atrial function reserve correlated with heart rate increase. Atrial response to dobutamine stress did not differ between patients with a dominant LV versus RV. Resting atrial minimal volume was higher in patients with moderate-to-severe AV regurgitation compared with those without. No differences in atrial function (reserve) was seen between patients with and without significant AV regurgitation or across groups of AV connections.Parameters of atrial and ventricular parameters during rest and dobutamine stress are shown in 2, p=0.001). Conversely, patients with a dominant LV increased their heart rate more than patients with a dominant RV (24.1 (11.7–32.2) vs 16.5 [(1.0–23.7) bpm, p=0.027). Patients with a dominant LV had a larger decrease of early filling volume during dobutamine stress, compared with those with a dominant RV (−3.7 (−7.2 to 0.2) vs −1 (−2.6 to 1.5) mL/m2, p=0.043)Lower ventricular early filling volume reserve and higher early peak filling rate reserve were related to higher heart rate increase during dobutamine stress (p<0.015). No other parameters were related to heart rate increase. During dobutamine stress patients with a dominant RV increased their stroke volume more than patients with a dominant LV (4.5 (1.9–8.6) vs −0.2 (−3.9 to 2.6) mL/mPatients with moderate-to-severe AV regurgitation had higher ventricular stroke volume reserve compared with those without. No other parameter of ventricular function differed between patients with and without significant AV regurgitation. Diastolic ventricular function (reserve) did not differ across groups of AV connections.Predictors of peak oxygen uptake and VE/VCO2 slope are shown in During a 7.1 (6.0–8.2) years follow-up 22 patients (39%) experienced a clinical event. Two patients died during the follow-up. Five patients underwent reoperation and an additional seven patients underwent interventional procedures. Thirteen patients experienced arrhythmia . One-year event-free survival estimate was 91% (84%–99%). Five years event-free survival estimate was 75% (95% CI 64% to 87%). Predictors of events during the follow-up are shown in We assessed atrial function and diastolic ventricular function at rest and during dobutamine stress in a cohort of young staged TCPC patients. We noted that atrial early and late emptying increased during the dobutamine stress CMR, rather than conduit volume. For ECC patients atrial early emptying volume reserve related to peak oxygen uptake. This has not been demonstrated at rest.The atria are important to provide adequate drainage of pulmonary venous blood in the, often preload impaired, single ventricle in the Fontan circulation. As different complex congenital heart diseases can necessitate a Fontan palliation, the morphology and connections of the atria is highly variable in this patient population. Atrial isomerism, double inlet or absent AV connections and one or two AV valves, including hypoplastic AV annuli are all part of the morphological spectrum of univentricular hearts. This might affect the haemodynamic relationship between the atria and both the pulmonary venous drainage and inflow into the single ventricle. In this study and with current methodology, we could not demonstrate an effect of dominant ventricular morphology or type of AV connection.Different surgical modifications of TCPC manipulate the atria in different ways. Atrial scarring as a result of surgery might disturb the compliance and pump function of the atrium. The ECC bypasses the atria completely, whereas the ILT modification creates a baffle in the right atrium using either prosthetic or tissue material.Little is known about the normal atrial response to dobutamine stress. During exercise atrial, early and late emptying increase.17Power loss in the Fontan circuit has been studied extensively, but the pulmonary venous atrium has received little attention in this respect.In long-standing diastolic dysfunction in structurally normal hearts, atrial pressure increases to maintain early ventricular filling.In previous research we demonstrated that the single ventricular reserve during low-dose dobutamine stress, a measure of systolic function, relates to clinical events during long-term follow-up.Several limitations of our present study should be considered. The lower temporal resolution of SSFP CMR, compared with echocardiography, can lead to underestimation or overestimation of parameters of diastolic function.Invasive measurements of atrial and ventricular pressure were not assessed due to the retrospective and non-invasive nature of our study. Non-invasive estimates of ventricular filling pressures, such as echocardiographic E/e’ were well within the normal range in a previous study including similar patients.9Dobutamine stress is considered to mimic exercise physiology. However, exercise-induced changes in respiration and activity of the lower extremities muscles could affect ventricular filling in the Fontan circulation. As respiration has a considerable effects on ventricular filling, imaging was obtained during free breathing. The contribution of respiration to ventricular filling is not exacerbated during the exercise.29 30We assessed a large number of both atrial and ventricular parameters for multiple clinical outcomes. To minimise the probability of type 1 errors  corrections for multiple testing were applied. Despite the relatively large sample size, the penalty for multiple testing with a large number of parameters hampered statistical power. Future research replicating our results could confirm associations which were considered statistically significant before applying this penalty.We assessed the function of the pulmonary venous atrium and diastolic function of the single ventricle during resting conditions and dobutamine stress for Fontan patients of contemporary surgical modifications. Dobutamine stress increases atrial early and late emptying, rather than conduit volume. Atrial early emptying volume reserve relates to exercise capacity for patients with an ECC Fontan modification. No other parameters of atrial or ventricular diastolic function predicted outcomes. Atrial stress testing might demonstrate occult dysfunction and increase insight in ventricular inflow impairment seen in these patients.


Riociguat is a soluble guanylate cyclase stimulator approved for the treatment of pulmonary hypertension. Its effect on cardiometabolic efficiency is unknown. A potential cardiac energy sparing effect of this drug could imply a positive prognostic effect, particularly in patients with right heart failure from pulmonary hypertension.We infused Riociguat in six healthy juvenile pigs and measured the integrated cardiovascular effect and myocardial oxygen consumption. To assess the interplay with NO‐blockade on cardiac function and efficiency we also administered the NO‐blocker L‐ NAME to the animals after Riociguat.2) and total mechanical work  were unaffected by Riociguat. In contrast, systemic and pulmonary vasoconstriction induced by L‐NAME (15 mg/kg) shifted the Ees/Ea ratio toward reduced SWeff in both systemic and pulmonary circulation. However, there was no surplus oxygen consumption, that was measured by the MVO2/PVA relationship after L‐NAME in Riociguat‐treated pigs. This suggests that Riociguat can reduce the NO‐related cardiometabolic inefficiency previously observed by blocking the NO pathway.Infusion of 100 µg/kg Riociguat gave modest systemic vasodilatation seen as a drop in coronary and systemic vascular resistance of 36% and 26%, respectively. Right and left ventriculoarterial coupling index (Ees/Ea), stroke work efficiency (SWeff), and the relationship between left ventricular myocardial oxygen consumption (MVO The sGC stimulator Riociguat hamper the energy wasting effect of NO‐blocade in Health juvenile pig hearts The circulating volume was maintained by a 20 ml·kg‐1·hr−1 continuous infusion of 0.9% NaCl supplemented with 1.25 g·L−1 glucose. Following sternotomy, the pericardium was removed, and the coronary arteries and pulmonary trunk were dissected free from connective tissue. The hemiazygos vein was then ligated.The pigs were premedicated with an intramuscular injection of 20 mg/kg ketamine  and 1 mg of atropine . Anesthesia was induced by intravenous injection of 10 mg/kg pentobarbital sodium  and 0.01 mg/kg fentanyl . The animals were ventilated after intubation. Normal ventilation was defined as an PaCO2.3A 7‐Fr pressure catheter  was inserted through an introducer sheath via the carotid artery into the left ventricle. A 5 Fr Swan‐Ganz catheter  was advanced into the pulmonary artery. A 5 fr balloon catheter was floated from the superior caval vein into the right ventricle for pressure measurements. Central venous pressure was measured in the right atrium. The systemic arterial pressure was assessed from a vascular catheter in the abdominal aorta. An 8 Fr balloon catheter was introduced into the inferior caval vein and positioned just below the right atrium for intermittent preload reduction. A 4 Fr catheter with side holes was placed in the coronary sinus for the collection of coronary venous blood. Transit time flow probes  were placed around the pulmonary trunk and the three coronary arteries. Eight sonometric crystals  were implanted subendocardially, as described in Figure 2.4The Riociguat dose was based on a dose‐response study in four animals  was then given as an intravenous bolus, and the second recording was carried out after another 30 min. Finally, L‐NAME (15 mg/kg) was given, also as a bolus. The dose of L‐NAME was based on an earlier dose‐response study in our lab  and a 1:1 solution of Transcutol, Diethylene glycol ethyl ether  and Cremophor, macrogolglycerol ricinolate . We used 5% Transcutol and Chremophore solutions, and the volume ratio between DMSO, Transcutol, and Chremophore was 0.05:2.5:2.5. This solution was then further diluted with 0.9 mg・ml2.5Data were sampled, digitized and analyzed . Cardiac dimension data, obtained by the sonometric crystals , an abrupt reduction in preload was carried out by rapid inflation of the balloon catheter situated in the caval vein. Example loops from the left and right ventricle are presented in Figure 0 was calculated at baseline for each pig and used as a constant for the remainder of the experiment. Arterial elastance, Ea, in both ventricles was calculated as.DESP is the end‐systolic pressure, and SV is the stroke volume / pressure–volume area (PVA) , EDP is the end‐diastolic pressure in the ventricle (mmHg), and SV is the stroke volume (ml). Pressure–volume area (PVA) was calculated as SW + potential energy (PE):P0 is the x‐axis intercept of the regression line of the end‐systolic pressure–volume relation at baseline.ESV is the end‐systolic volume (ml), EDV is the end‐diastolic volume (ml), and V2) at various workloads, where MVO2 was calculated as:Left ventricular mechanoenergetic efficiency was assessed by the linear regression of PVA and myocardial oxygen consumption , LVCBF is the left ventricular coronary blood flow (ml/min) or blood flow through the circumflex and left anterior descending arteries divided by left ventricular weight (LVW in gram (g), as described , and 20.2 is a factor for J/mL O2 to convert MVO2 to mechanical energy equivalents. In the MVO2/PVA framework the y‐axis intercept represents myocardial oxygen cost for excitation–contraction coupling and basal metabolism, while 1/slope represents cardiac efficiency of contractile work , avdO2.62 and the product of MVO2 and the dummy variable for medication were used as fixed effects  and a statistical package . Values are presented as the mean ± standard deviation. Mixed model analysis with pig identity as random effect, with allowance for variation in both intercept and slopes between pigs, was performed on the graph in Figures 33.1‐1, 111 ± 14 min‐1 and 111 ± 11 min‐1, respectively, with no significant difference (Table Increasing doses of Riociguat up to 100 µg/kg induced progressive systemic vasodilatation and hypotension. No significant effects were seen in the pulmonary vasculature. At the maximum dose tested the mean systemic pressure reached the predefined threshold of 50 mmHg (manuscript in press). Heart rates in the control state during Riociguat infusion and after L‐NAME bolus were 112 ± 9 min3.2p = .01) and 26% ± 18% (p = .00), respectively  and 1.5 ± 0.2 (p = .00) fold increase in PVR and SVR, respectively.A bolus of the NOS inhibitor L‐NAME (15 mg/kg) after Riociguat resulted in both pulmonary and systemic vasoconstriction as seen by a 2.5 ± 1.6 (3.3p = .00), while no change in this index was seen for the right ventricle. Stroke work was reduced by 20% ± 8% (p = .00) for the left, but not the right ventricle. Left ventricular end‐systolic pressure–volume relation, i.e., elastance (LV Ees), was reduced by 14% ± 14% (p = .01). Right ventricular elastance (RV Ees), remained stable. Preload recruitable stroke work (PRSW) decreased by 13% ± 7% (p = .01) for the left ventricle but did not change for the right ventricle. The diastolic relaxation index, Tau, was unaltered for the left ventricle. Ventricular dimensions remained unchanged.The bolus of Riociguat did not alter cardiac output or ejection fraction Figure . Left vep = .00) and left ventricular ejection fraction (EF) decreased from 33% ± 5% to 25% ± 4% (p = .00). Heart rate was unchanged. Reduction in EF was accompanied by an increase in end‐systolic volumes for both ventricles; 11% ± 8% (p = .010) for the left ventricle and 12% ± 10% (p = .04) for the right ventricle. Left ventricular elastance increased by 29% ± 23% (p = .01) and right ventricular elastance increased by 18% ± 10% (p = .02) , while no effect was found on right ventricular PRSW.L‐NAME decreased cardiac output by 23% ± 7%  and 25% ± 10% (p = .00)  and chronic thromboembolic pulmonary hypertension (CTEPH), two out of five categories of pulmonary hypertension (PH), according to the World Health Organization , ventriculoarterial matching (Ees/Ea ratio) and left ventricular pump efficiency (SW efficiency) were overall minor. The model is therefore well designed to pick up relatively minor direct metabolic or oxygen‐consuming effects of test‐drugs. Using the same experimental setup, in earlier studies, we have shown that NO‐blockade, inotropic drugs and systemic infections have clear metabolic effects in the myocardium evaluated in the frame of an MVOThere is consistent evidence that blocking enzymes in the NO pathway causes reduced cardiac efficiency by surplus myocardial oxygen consumption  after infusion of the NO‐precursor l‐arginine. In that study the authors also observed the predicted opposite effect by infusion of a NO synthetase inhibitor  has been approved for treatment in pulmonary hypertension based on pulmonary vasodilatory effects in animal disease models and human studies. The effect of this sGC stimulator is therefore different in healthy and diseased lung vasculature.52 in the heart after blocking the endogenous NO‐tone by L‐NAME was attenuated by this dose of Riociguat. This oxygen‐conserving effect during L‐NAME stimulation indicates that Riociguat can induce “metabolic protection” in stressed myocardium and potentially also in pathological states. Such a potential should be explored in experimental disease models and during various pharmacological combinations.Riociguat alone has no effect on myocardial oxygen consumption in the healthy heart. Both ventriculoarterial coupling and basal myocardial oxygen metabolism are unaffected by infusion of 100 µg/kg Riociguat. However, the subsequent administration of L‐NAME did not increase the relative oxygen consumption in the myocardium, and this suggests that the expected surplus basal MVO6The data used for the study can be shared upon personal contact with the authors.None of the authors has any conflicts of interest.Torvind Næsheim: Drafting protocol, sourcing medications, setting up the lab, instrumentation, data collection, analysis, and authoring; Ole‐Jakob How: Idea, analysis, authoring; Truls Myrmel: Idea, drafting protocol, instrumentation, data collection, analysis, and authoring.The research complies with the ethical guidelines of animal research as given by the the Norwegian Animal Research Authority. The protocol was approved in advance with the reference number FDF 2012/55972.


Acquiring high-quality cardiac magnetic resonance (CMR) images in patients with frequent ventricular arrhythmias remains a challenge. We examined the safety and efficacy of procainamide when administered on the scanner table prior to CMR scanning to suppress ventricular ectopy and acquire high-quality images. Fifty consecutive patients  were scanned in a 1.5 T scanner using a standard cardiac protocol. Procainamide was administered at intermittent intravenous bolus doses of 50 mg every minute until suppression of the ectopics or a maximum dose of 10 mg/kg. The average dose of procainamide was 567 ± 197 mg. Procainamide successfully suppressed premature ventricular contractions (PVCs) in 82% of patients, resulting in high-quality images. The baseline blood pressure (BP) was mildly reduced , while the baseline heart rate (HR) remained relatively unchanged (mean HR change −1 ± 6 bpm). None of the patients developed proarrhythmic changes. Bolus intravenous administration of procainamide prior to CMR scanning is a safe and effective alternative approach for suppressing PVCs and acquiring high-quality images in patients with frequent PVCs and normal or only mildly reduced systolic function. Cardiac magnetic resonance (CMR) provides excellent assessment of cardiac morphology and function and enables detailed myocardial tissue characterization with a high degree of precision . Using tAn alternative approach to improve image quality when scanning patients with frequent PVCs is the administration of antiarrhythmic medication prior to the scan. The ideal antiarrhythmic for this purpose should have a quick onset but a relatively short duration of action, allowing intravenous (i.v.) administration on the scanner table without the need for further monitoring. Procainamide is a class Ia antiarrhythmic agent which has such features.We examined the safety and efficacy of procainamide when administered on the scanner table prior to CMR scanning for suppressing ventricular ectopy and acquiring high quality images.2, an allergy to gadolinium-based contrast agents, any contraindication to the MR environment , pregnancy, claustrophobia, ECG contraindications to procainamide  and patients with a severely reduced ejection fraction on the echocardiogram for safety reasons, as it was not planned for them to stay in the hospital for prolonged hemodynamic monitoring.The study included 50 consecutive adult patients  referred for a CMR scan due to frequent PVCs or non-sustained ventricular tachycardia on an electrocardiogram (ECG) or a 24 h Holter monitor. The inclusion criteria were a high PVC burden (bigeminy or trigeminy) during CMR scanning that significantly affected image quality and no prior history of heart failure. The exclusion criteria were an estimated glomerular filtration rate <30 mL/min/1.73 mThe CMR studies were performed on a 1.5 T Magnetom Avanto  scanner using phased-array radiofrequency receiver surface coils and dedicated cardiac software. The images were obtained with breath-holding instructions and ECG gating. A standard cardiac protocol was used, including balanced steady state free precession cine images , T2-weighted fat-suppressed turbo spin echo imaging  and late gadolinium enhancement (LGE) imaging . An operator graded the image quality of the cine images before and after procainamide administration. A 1–4 scale system was used: 4 indicated no artifacts and excellent image quality; 3 indicated minor artifacts with overall good image quality; 2 indicated moderate artifacts significantly affecting image quality and the accuracy of the analysis; and 1 indicated major artifacts, with the scan not able to be analyzed at all.®, vial 1 g/10 mL) was administered on the scanner table at intermittent i.v. bolus doses of 50 mg every minute until the suppression of PVCs was achieved or a maximum dose of 10 mg/kg was reached  for Windows. We present continuous variables as means (SDs) or medians (25th to 75th percentile), as appropriate. Normality of distribution was tested using the Shapiro-Wilk test. Categorical variables are presented as percentages. Paired t-tests were used to compare the blood pressure and heart rate response of the patients, as well as the image quality before and after procainamide administration. All tests were two-sided, and α was set at 0.05.The majority of the patients (73%) were being treated for their ventricular arrhythmia with oral b-blockers, 7% were on flecainide  and another 7% were receiving amiodarone, while 13% were not prescribed any treatment by the referring physician. The average dose of procainamide administered intravenously on the scanner table prior to CMR scanning was 567 ± 197 mg (range of 200–1000 mg) with an average duration of administration of 11 ± 4 min. Procainamide successfully suppressed PVCs in 82% of patients , enabling the use of arrhythmia detection and sorting algorithms) resulting in high-quality cine imaging when compared with the initial image . In sevep < 0.001; diastolic BP −4 ± 9 mmHg, p = 0.012), but none of the patients developed symptomatic hypotension. There was no significant change in heart rate (HR)   after procainamide administration  .CMR in patients with irregular heart rates, including frequent PVCs, remains challenging due to artifacts. Our study showed that i.v. bolus procainamide successfully suppressed PVCs in 82% of patients with ventricular arrhythmias and significantly improved the image quality, enabling accurate measurements. Procainamide administration on the scanner table was not only effective, but also safe in our group of patients with normal or mildly reduced systolic function.CMR imaging in patients with arrhythmias constitutes a valuable diagnostic and prognostic tool. More specifically, CMR provides information regarding the underlying cause of and accurately assesses ventricular systolic function, which has been shown to predict adverse cardiac events. The pattern, location and extent of scarring or fibrosis can predict the improvement of cardiac function with treatment as well as future arrhythmic risk , in addiCardiac motion during scanning constitutes a major source of image degradation and artifacts in CMR imaging. The problem is solved by ECG-gated image acquisition throughout the cardiac cycle, divided into different phases, and then image reconstruction from the information acquired over several heart beats. When the heart rate is irregular, beat-to-beat variations of the R-R interval cause artifacts during image reconstruction, resulting in significantly impaired image quality ,13. In pAnother approach to improve CMR image quality is the administration of an antiarrhythmic medication prior to the scan. We selected i.v. procainamide as an antiarrhythmic agent due its favorable profile in the treatment of ventricular arrhythmias in the acute setting. Procainamide is a class Ia antiarrhythmic agent, whose primary mechanism of action is through inhibition of the rapid inward sodium current, INa. It acts by delaying repolarization and increasing the effective refractory period of atrial and ventricular fibers. The conduction velocity and excitability are also decreased progressively as the drug concentration increases . The abiPossible acute adverse reactions to procainamide include heart block, bradycardia, tachyarrhythmias or hypotension. Moreover, in patients with severely reduced systolic function, procainamide should be administered with caution because it may produce negative inotropic effects . In the Some limitations of this study should be acknowledged. The study group was relatively small, and further studies are needed to assess safety and efficacy in more diseased cohorts of patients . This is important as PVCs are common in patients with heart failure and reduced ejection fraction . Only 8%We propose an alternative approach for high-quality CMR imaging in patients with frequent ventricular arrhythmias and normal or only mildly impaired LV systolic function , which appears to be both effective and safe for PVC suppression in this group of patients.