Ultrasonographic measurements of inferior vena cava (IVC) diameters and right ventricle (RV) volumes are important tools for the evaluation of intravascular volume. The current study investigates the association of IVC diameters and RV volumes before colonoscopy in prediction of postanesthesia hypotension.Seventy patients scheduled for colonoscopy were included in the study. Preoperatively, expirium (dIVC max) and inspirium (dIVC min) IVC diameters were measured using M-mode ultrasonography and the collapsibility index (IVC-CI) was calculated. Ventricular volumes and areas were also measured using transthoracic echocardiography. Postanesthesia hypotension was defined as mean arterial blood pressure of <60 mmHg or a decrease of >30% in the mean arterial pressure after sedation. Minimum and maximum IVC diameters were significantly lower  and IVC-CI was significantly higher (P < 0.001) in patients who developed hypotension. Similarly, right ventricular end-diastolic area (RV-EDA), right ventricular end-systolic area (RV-ESA), right ventricular end-diastolic volume (RV-EDV), right ventricular end-systolic volume (RV-ESV), and left ventricular end-systolic volume (LV-ESV) values were significantly lower in patients with hypotension (P < 0.05). Logistic regression analysis showed that dIVC min and RV-ESA were independent predictors of hypotension. IVC diameters and RV-ESA, RV-EDA, RV-ESV, and RV-EDV are good indicators of preoperative volume status and can be used to predict the patients at risk of developing hypotension. Anesthesia may cause hemodynamic instability and hypotension in the perioperative period. Perioperative blood pressure instability is clinically important because it is associated with cardiac, renal, and neurologic adverse events . Volume status has a major impact on the maintenance of perioperative hemodynamic homeostasis; therefore, accurate evaluation prior to operation is important. Several patient- and procedure-related factors, such as physical status of the patient, comorbidities, and preoperative interventions such as bowel preparation and long fasting duration, may affect preoperative volume status [3]. Various methods have been described for accurate preoperative estimation of volume status, and methods used to evaluate volume status have evolved from static pressure and volume parameters to dynamic indices [4].Ultrasonographic measurements of inferior vena cava (IVC) diameters and right ventricular (RV) volumes are important tools in the evaluation of preoperative intravascular volume status and response to fluid therapy [5]. Hand-carried cardiac ultrasound (HCU) can be used for these measurements, and there are acceptable accuracy rates in cardiac evaluation of these parameters by noncardiologists . Transthoracic echocardiography (TTE) enables rapid evaluation of anesthetized and awake patients and eliminates the need for invasive monitorization of the circulation status [2]. Preoperative respiratory variation of IVC has been shown to predict hypotension after induction under general anesthesia with high sensitivity and specificity [8]. In this context, the objective of the current study was to evaluate the predictive power and correlation of USG measurements of vena cava inferior diameters and right ventricular volumes for prediction of postanesthesia hypotension in patients undergoing colonoscopy with sedoanalgesia.This study was conducted in the gastroenterology outpatient clinic of the Necmettin Erbakan University Meram Faculty of Medicine Hospital as a single-center observational study between January 2018 and August 2018 after receiving the necessary approval from the local ethics committee, in accordance with the Declaration of Helsinki. The participants were informed about the study in detail both verbally and in writing, and all patients provided informed consent. A total of 70 patients aged over 18 years with an American Society of Anesthesiologists (ASA) physical status classification of I–III who were scheduled for colonoscopy under sedation were included in the study. All patients underwent bowel preparation before the operation. This preparation entailed a clear diet in all patients 2 days before the operation, a laxative solution containing 20 mL of sennoside A-B and calcium salt  24 h before the operation, and a watered enema given in 8-h intervals. Patients were told that they could drink particle-free clear fluid until 3 h before the procedure. Patients with increased intraabdominal pressure, heart failure, valvular disease, portal hypertension, a difficult airway, or chronic obstructive pulmonary disease; those using diuretics; pregnant patients; and those with peripheral vascular disease, autonomic nervous system disease, mental disorders, or a history of pulmonary hypertension were excluded from the study. Demographic data , ASA classification, and preoperative fasting times were recorded for all patients. After routine monitorization, baseline values of blood pressure, heart rate, and peripheral oxygen saturation were recorded. After the procedure, the Modified Aldrete Score (MAS) was used to measure the recovery. Patients were discharged to their homes when the MAS was 10, and the time it took for each patient to reach a MAS score of 10 after the procedure was recorded. Ultrasonographic IVC measurements were performed while patients were in a supine position before colonoscopy with a Mindray ultrasound device. Measurements were obtained in the abdominal mode and a sector probe was used. IVC ultrasonography was performed for each patient according to the methodology described by the American Echocardiography Society, with a subcostal approach using an intermediate median long-axis image. A two-dimensional IVC image was acquired beginning from the right atrium, and respiratory changes in IVC diameters were gathered 2–3 cm distal to the right atrium. Expirium (dIVC max) and inspirium (dIVC min) diameters were measured at least 3 times in M-mode and the collapsibility index (IVC-CI) was calculated according to the formula IVC-CI = (dIVC max – dIVC min) / IVC max × 100. Data of patients were excluded if there was a difference higher than 0.2 cm in dIVC max measurements between any 2 images. The USG mode was then changed to heart mode and patients were moved to a left decubitus position. Apical imaging of the RV and left ventricle (LV) was obtained using harmonic imaging with a transthoracic 3-MHz phase sector transducer (Mindray M7 ultrasound device). The end-systolic area (ESA) and end-diastolic area (EDA) were measured for both right and left ventricles. The volumes of the cardiac chambers were assessed with the Simpson method. The RV end-diastolic volume (EDV), RV end-systolic volume (ESV), and ejection fraction (EF) measurements were obtained using software loaded to the ultrasonography device. The EDV was measured when the tricuspid valve was closed, and ESV was measured via the smallest RV chamber image. Both measurements were made from the apical four-chamber view by tracing the endocardial margin of the RV. The two-dimensional echocardiography subtraction method was obtained from the apical four-chamber view by tracing the volume of the LV with the inclusion of the interventricular septum and subtracting it from the total volume of the LV and RV. After these measurements were taken, standard deep sedation (Ramsey sedation score: 5–6) was performed by an anesthetist who was not involved in the study. Each patient was administered 0.01–0.03 mg/kg midazolam, 0.1–1 µg/kg fentanyl, and 1–2 mg/kg propofol. Additional doses were administered during the operation as needed. The agents and doses used in sedation were recorded. Routine monitorization continued in the operating room. Blood pressure measurements were performed using a noninvasive oscillometric method. Patients’ heart rate, blood pressure, and peripheral oxygen saturation (SpO2) measurements were assessed every 2 min from sedation until the end of the colonoscopy procedure. Postanesthesia hypotension was defined as mean arterial pressure (MAP) of <60 mmHg or a decrease of >30% in MAP after sedation.Results of the study were analyzed with SPSS 19.0 for Windows . Continuous variables were expressed as mean ± standard deviation and categorical variables as number and percentage . Normal distribution of the data was analyzed with the Kolmogorov–Smirnov test, histograms, and ±SD. Nonparametric data of the groups were compared with the Mann–Whitney U test and parametric data with the independent sample t-test. Categorical data were analyzed with the chi-square test. ROC curve analyses were performed in order to test the ability of preoperative dIVC max, dIVC min, IVC-CI, RV-ESA, RV-EDA, RV-ESV, and RV-EDV in prediction of clinically significant hypotension in the perioperative period. Sensitivity, specificity, and positive and negative predictive values were calculated for optimal cut-off values. Correlation between hypotension and ultrasonographic data was evaluated with Spearman’s correlation analysis. P < 0.05 was considered statistically significant.A total of 70 patients scheduled for colonoscopy under sedation were included in the study. The mean age of the patients was 49.9 ± 15.03 (19–79) years, and the male/female ratio was 32/38 (45.7% vs. 54.3%). Eighteen (25.7%) patients developed hypotension after sedation. Demographic and baseline hemodynamic data of the whole study group and demographic and hemodynamic data of the patients who developed hypotension after sedation are shown in Table 1. Demographic characteristics and baseline hemodynamic data were found to be similar in patients with and without hypotension (P > 0.05). On the other hand, a significant difference was found between these 2 groups in terms of systolic arterial blood pressure (SAP), diastolic arterial blood pressure (DAP), and MAP assessed after sedation, as would be expected (P < 0.05). Fasting durations were also statistically significantly longer in the patients who developed hypotension (P = 0.04). Doses of hypnoid and opioid drugs used for sedation were found to be similar between the patients with and without hypotension (P > 0.05).In USG evaluation, IVC diameters were significantly lower and IVC-CI was significantly higher in the patients who developed hypotension (P < 0.05). Similarly, in the evaluation of cardiac chambers, RV-EDA, RV-ESA, RV-EDV, RV-ESV, and LV-ESV values were found to be significantly lower in the patients who developed hypotension (P < 0.05). Preprocedural ultrasound measurements of cardiac chambers and IVC diameters in patients with and without hypotension are summarized in Table 2. ROC analyses were carried out for each of the measured parameters to test the ability to predict hypotension developing after sedation. Among tested parameters, the best results were obtained with IVC-CI and dIVC, both of which showed good diagnostic accuracy. For IVC-CI, the calculated AUC was 0.854 , and the specified optimal cut-off value of 45% yielded 83.3% sensitivity and 82.7% specificity. For this cut-off value, positive and negative predictive values were 62.5% and 93.5%, respectively. For dIVC, the AUC was 0.866 . The optimal cut-off value of dIVC min was found to be 1 cm, with 94.4% sensitivity and 71.2% specificity. Calculated positive and negative predictive values were 53.1% and 97.3%, respectively. ROC analyses are summarized in Table 3.There was a strong positive correlation between hypotension and IVC-CI , while strong negative correlations were found between hypotension and dIVC max , dIVC min , RV-ESA , and RV-EDA  (Table 4).Logistic regression analysis showed that dIVC min  and RV-ESA  were independent predictors of hypotension.In the present study, we found that ultrasonographic evaluation of IVC, RV-ESA, RV-EDA, RV-ESV, and RV-EDV before colonoscopy predicted and were correlated with hypotension developing after sedation. In clinical practice, routine monitorization of physiological parameters such as heart rate, arterial blood pressure, central venous pressure, peripheral oxygen saturation, and urine output is often used for assessment of intravascular volume and guide fluid therapy. However, the sensitivity and specificity of these parameters in determining subclinical hypovolemic or hypervolemic conditions are low. Therefore, the use of the static parameters described above in order to manage perioperative fluid therapy may cause hypovolemia or hypervolemia . Similarly, in our study we found that there was no significant difference in baseline arterial pressure values between the patients who developed hypotension after sedation and those who stayed hemodynamically stable with no significant change in arterial blood pressure. It has been shown in previous studies that there is no correlation between static hemodynamic data such as central vein pressure and pulmonary arterial occlusion pressure and IVC measurements . Therefore, we used measurements of IVC together with cardiac chambers in our study, and good correlation was observed between these 2 dynamic monitorization methods. There are some risk factors associated with the development of postanesthesia hypotension in patients undergoing colonoscopy. First of all, preoperative fasting and bowel preparation may cause hypovolemia [12]. Our findings are also consistent with this because the mean fasting time was significantly longer in patients who developed hypotension after sedation. IVC diameter is not affected by the compensatory vasoconstrictor response given by the body to volume loss, and it is a reliable indicator of blood loss even in the small quantity of 450 mL . Previous studies have shown that ultrasonographic measurement of IVC diameter may be a rapid and noninvasive method for clinicians in the evaluation and management of critical patients . Recent clinical studies have also demonstrated that the most reliable measurement of IVC diameter can be made at 2 cm caudal from the hepatic vein and IVC junction . Therefore, in our study IVC diameters were assessed using this technique, and measurement errors were minimized. We observed that IVC diameters were effective in the prediction of hypotension, which may develop in patients under sedation, and optimal cut-off values were 45% for IVC-CI, 1.51 cm for IVC max, and 1.0 cm for IVC min. Our findings also showed that IVC min was an independent predictor of hypotension in regression analyses. Similar results were also reported in the literature . In a recent study, Salama et al. reported that IVC-CI was significantly higher in patients who developed postspinal anesthesia hypotension than in patients who did not [21]. Also, in the study conducted by Saranteas et al., it was found that preoperative dIVC max/IVC-CI predicted spinal-induced hypotension better than echocardiographic measurements [22]. Noninvasive transthoracic echocardiography (TTE) examination is possible using portable ultrasound systems [23–27]. This method has been used for the evaluation of critical patients since it enables rapid assessment of volume and contractility of both ventricles. TTE is helpful in screening serious pathologies, and it is generally considered sufficient in evaluation of cardiac function and volume load. Although it does not allow for a comprehensive cardiac examination, this screening may directly affect patient management in the perioperative period . Our results are also in parallel with the literature in this aspect. The results of the current study showed that preoperative TTE examination and right ventricular measurements were important tools in the prediction of hypotension developing in the perioperative period. TTE examination can be considered as a simple and effective tool to evaluate the volume status of patients preoperatively, and it can be used in the perioperative management of patients. In the current study, diagnostic accuracy when using RV end-systolic and end-diastolic area and volumes was found to be lower compared to the use of IVC measurements, but there were still strong negative correlations between RV-ESA, RV-EDA, and hypotension. RV-ESA was also found to be an independent predictor of hypotension in the logistic regression analysis.The use of perioperative/intraoperative echocardiography by an anesthesiologist may change the management of these patients and improve possible negative outcomes [29]. This method is an adjuvant technique for anesthesiologists in directing perioperative clinical management [30]. Kratz et al. showed that focused TTE performed by an anesthesiologist is an effective tool that provides important data in the hemodynamic management of unstable patients, and they encouraged the use of TTE in perioperative medicine to provide better and more sustainable care in particularly complex cases [31].In our study, a considerable proportion of the patients (25.7%) developed hypotension under sedation, and noninvasive evaluation of IVC diameters and right cardiac chambers in these patients before sedation was found to be helpful in the prediction of possible hypotension. In this context, we believe that preoperative evaluation of IVC diameters and right cardiac chambers would guide hemodynamic management of the patients in the perioperative period, and therefore necessary measures can be taken early for patients with increased risk.The current study has several limitations. First of all, all echocardiographic measures were made by an operator with experience at a basic level. However, we believe that this is not a critical issue because acceptable accuracy rates were reported in the literature in cardiac evaluation by noncardiologists using cardiac ultrasound . It is also important to note that perioperative echocardiography performed by an anesthesiologist is not an alternative to detailed echocardiographic examination performed by experienced cardiologists; rather, it is an additional tool for the anesthesiologist in guiding perioperative management [31]. Second, the measurements were performed only before the operation and could not be made after sedation because of patient positioning and limited setting. Third, a single end-systolic and end-diastolic measurement of RV and LV areas and volumes with TTE may lead to faulty insight for recognition and evaluation of volume status due to dynamic variability. Therefore, serial measurements would be better in order to assess volume status more sensitively.In conclusion, preoperative dynamic measurements of IVC diameters and right ventricular area and volumes are important tools for the evaluation of the preoperative volume status of patients undergoing colonoscopy with IV sedoanalgesia. These measurements can easily be obtained in outpatient clinical settings and can be used in prediction of postanesthesia hypotension. Preoperative measurement of CI and dIVC min predict the incidence of hypotension after induction with high sensitivity and specificity. Sensitivity and specificity are lower for RV measurements compared to IVC measurements, and RV measurements can be used in patients where IVC measurements are impossible or inconclusive. dIVC max, dIVC min, RV-ESA, and RV-EDA are correlated with hypotension, and dIVC min and RV-ESA are independent predictors of hypotension. Further studies are needed to determine fluid therapy strategies based on the measurements of IVC/RV areas and volumes in order to prevent postanesthesia hypotension.


Background: Increasing left ventricular mass in hypertensive patients is an independent prognostic marker for adverse cardiovascular outcomes. Genetic factors have been shown to critically affect left ventricular mass. AGT M235T is one of the genetic polymorphisms that may influence left ventricular mass due to its pivotal role in the regulation of plasma angiotensinogen level as well as hypertension pathophysiology in Asian populations. Currently, how M235T affects left ventricular mass is not well-described in Vietnamese hypertensive patients. This study aimed to investigate the association between M235T and left ventricular mass in Vietnamese patients diagnosed with essential hypertension.Materials and Methods:AGT M235T genotyping and 2D echocardiography were performed on 187 Vietnamese subjects with essential hypertension. All the ultrasound parameters were obtained to calculate the left ventricular mass index according to the American Society of Echocardiography and the European Association of Cardiovascular Imaging 2015 guidelines. Other clinical characteristics were also recorded, including age, gender, duration of hypertension, hypertensive treatment, lifestyle, renal function, fasting plasma glucose, and lipid profile.Results: MT and TT genotypes were determined in 30 and 157 subjects, respectively. AGT M235T genotype, duration of hypertension, body mass index, and ejection fraction statistically affected the left ventricular mass index, which was significantly greater in TT compared to MT carriers after adjusting for confounding factors.Conclusion: The TT genotype of AGT M23T was associated with greater left ventricular mass in Vietnamese patients diagnosed with essential hypertension. Essential hypertension is a major health-care burden globally, despite the availability of efficient antihypertensive agents . IncreasAGT M235T is one of the more promising markers showing an association with LVM in hypertensive patients. AGT M235T is characterized by the substitution of Threonine for Methionine in codon 235, and is well-proven to affect the plasma angiotensinogen concentration  in clothing without shoes. Height was determined without shoes on a wall-mounted stadiometer  with mandible plane parallel to the floor. Body mass index (BMI) was calculated as weight (kg) divided by the square of height (m)  ; body suight (m) . All infight (m) . Alcoholight (m) . Blood pight (m) . For hyp3-(LVDd)3) × 1.04 × 0.8 + 0.6 (g). LVMI (left ventricular mass index) was identified by the formula: LVMI = LVM/BSA (g/m2). Left ventricular hypertrophy was defined as LVMI >115 g/m2 for men or 95 g/m2 in women  with a 2–4 MHz transducer at the Cardiology Imaging Unit of the University Medical Center at Ho Chi Minh City. All the echocardiography parameters used for further analysis were the average of two measurements obtained blindly by two independent cardiologists with proper echocardiographical expertise according to the recommendations of the American Society of Echocardiography and the European Association of Cardiovascular Imaging 2015 guidelines , 35. Lefin women . Relativin women . Supplem™ Whole Blood Genomic DNA Purification Mini Kit . Four primers were designed for a tetra-primer allele-specific polymerase chain reaction (PCR) to identify M235T based on the sequence of the AGT gene (Genebank NG_008836). The length of control bands was 282 bp. Allele T and allele M were determined by the appearance of 118 bp and 204 bp bands, respectively. The sequences of primers are listed in Genomic DNA was extracted from patients' leukocytes using a GeneJet™ Nucleic Acid Dye .PCRs were performed using a Mastercycler@proS  with the following conditions: one cycle at 98°C for 3 min and 40 cycles of denaturation at 98°C for 20 s, annealing at 56°C for 20 s, extension at 72°C for 30 s, and final extension at 72°C for 2 min. The product length of PCR was identified by electrophoresis on 2% agarose gels with DiamondT-test and Chi-squared tests were performed for statistical analysis. Univariate analysis and multivariate logistic regression were used to assess the association between patients' characteristics and LVMI. All tests were considered significant if p ≤ 0.05.The data were encrypted to ensure blinded analysis. Data were input using Epidata 3.1 and subsequently analyzed using Stata 13.3 software. AGT M235T were found in 157, 30, and 0 individuals, respectively. The percentage of T and M alleles were 92 and 8%. The distribution of AGT M235T was under Hardy Weinberg equilibrium, with p = 0.49. Patients' characteristics are described in TT, MT, and MM genotypes of Echocardiography parameters are listed in 2) higher LVMI than MT-carrying subjects , and eGFR were not statistically different between TT and MT carriers. LVMI was significantly higher in TT compared to MT-carrying subjects even after adjusting for confounding factors, such as duration of hypertension, EF, and BMI. A similar association between M235T and LVM has been observed in Han Chinese G. This variant, which is in strong linkage with M235T, is located in the promoter region of AGT and has been shown to be the key player in regulating AGT transcription (Echocardiography is a reliable, cost-effective imaging technique to determine LVM. Its adoption has been extensively certified in clinical practice, as well as research , 38. In  Chinese  but not  Chinese , 27. The is <10% . The fre is <10% , 24, 39. is <10% –42. The  is <10% , 19, 24. is <10% . In addi is <10% . These b is <10% –47. Howe is <10% . Remarkaon study . The maicription . The lacIt has been proposed that the major T allele is associated with the upregulation of the angiotensinogen level and promotes sodium reabsorption, while the minor M allele is a recent “thrifty” mutation in humans to adapt to environmental changes in which sodium becomes widely available . The graAGT M235T genotype in Vietnamese hypertensive subjects. Specifically, the MM genotype was not detectable in our data. Second, the measurement of LV by 2D ultrasound is less correlated with cardiac magnetic resonance in assessing LVM compared to real-time 3D echography (AGT M235T per se cannot fully explain the difference in LVM between the genotype groups observed in this study. Therefore, further studies with larger sample sizes, comprehensive genetic analysis such as genome-wide association or whole genome sequencing, and advanced imaging techniques are required to better describe the association between genetic components and LVM in Vietnamese patients with essential hypertension.This study has several limitations that need to be discussed. First, the relatively small sample size may lead to a bias in identifying the hography . Third, AGT M235T and LVM in Vietnamese hypertensive patients emphasizes once again the significant effect of this genetic polymorphism in left ventricular hypertrophy pathophysiology in Asian populations.To the best of our knowledge, this is the first study to determine the association between genetic variants and LVM in Vietnamese patients diagnosed with essential hypertension. The association between The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by Ethics Committee of the University of Medicine and Pharmacy at Ho Chi Minh City, Vietnam. The patients/participants provided their written informed consent to participate in this study.MD, TT, TM, TKT, and HC designed the study. TT, HT, and SH included the patients to the study. LL, HV, and TM performed genotyping procedure. MD, TT, HT, SH, TKT, and HC analyzed the data. MD, TT, and TM wrote the manuscript. All authors critically revised the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Sepsis is characterized by various hemodynamic alterations which could happen concomitantly in the heart, pulmonary and systemic circulations. A comprehensive demonstration of their interactions in the clinical setting of COVID-19 sepsis is lacking. This study aimed at evaluating the feasibility, clinical implications, and physiological coherence of the various indices of hemodynamic function and acute myocardial injury (AMI) in COVID-19 sepsis.Hemodynamic and echocardiographic data of septic critically ill COVID-19 patients were prospectively recorded. A dozen hemodynamic indices exploring contractility and loading conditions were assessed. Several cardiac biomarkers were measured, and AMI was considered if serum concentration of high-sensitive troponin T (hs-TNT) was above the 99th percentile, upper reference.n = 36, 54%), echocardiography results prompted therapeutic changes. Mortality was not influenced by the echocardiographic variables in multivariable analysis. Cardiac biomarkers’ concentrations were most often increased with high incidence of AMI reaching 72%. hs-TNT was associated with mortality and inversely correlated with most of LV and RV contractility indices.Sixty-seven patients were assessed , with a median age of 61 [50–70] years. Overall, the feasibility of echocardiographic parameters was very good, ranging from 93 to 100%. Hierarchical clustering method identified four coherent clusters involving cardiac preload, left ventricle (LV) contractility, LV afterload, and right ventricle (RV) function. LV contractility indices were not associated with preload indices, but some of them were positively correlated with RV function parameters and negatively correlated with a single LV afterload parameter. In most cases (In this comprehensive hemodynamic evaluation in critically ill COVID-19 septic patients, we identified four homogeneous and coherent clusters with a good feasibility. AMI was common and associated with alteration of LV and RV functions. Echocardiographic assessment had a clinical impact on patient management in most cases.The online version contains supplementary material available at 10.1186/s40560-020-00516-6. The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents the greatest global public health crisis of the last decades. Approximatively, up to 40% of hospitalized patients develop severe pneumonia with sepsis requiring intensive care unit (ICU) admission . MultiplSystemic  and pulmThe aims of the present study were as follows: (i) first, to assess, in COVID-19 patients, the feasibility, clinical implications, and physiological coherence of the various indices of cardiac function in evaluating hemodynamics in sepsis; (ii) second, to assess the physiological correlates of acute myocardial injury in COVID-19 sepsis.We conducted a prospective observational monocenter study on all patients diagnosed with RT-PCR-confirmed SARS-CoV-2 sepsis (Sepsis 3 definition ) and conThe study was approved by the institutional ethical committee of the French Intensive Care Society as a component of standard care, and patient consent was waived. Written and oral information about the study was given to the families. Case severity was evaluated by Simplified Acute Physiology Score II (SAPS II) for acute illness at ICU admission and by Sequential Organ Failure Assessment (SOFA) score for organ dysfunction in sepsis. For patients in shock, norepinephrine was given as the first-choice vasopressor therapy . The patients were followed up until day 28.Acute myocardial injury (AMI) was diagnosed if serum concentration of high-sensitive troponin T (hs-TNT) surpassed the 99th percentile, upper reference level , 12, i.eTo evaluate cardiac function, transthoracic echocardiography (TTE) was performed within 72 h of ICU admission by trained operators  using an S7 or E9 ultrasound system . All echocardiography tests were carried out in strict respect to current guidelines for care of COVID-19 patients . We usedLV preload was assessed using the maximal diameter of inferior vena cava (IVC) and estimates of LV filling pressures (E/A and E/e′ ratios) on pulsed-wave Doppler and tissue Doppler upon measuring, for the former early (E) and late (A), and for the latter early (e′) diastolic wave velocity at the lateral mitral valve annulus. LV afterload was assessed using invasively measured diastolic arterial pressure (DAP), systemic vascular resistance (SVR), and end-systolic arterial elastance (AE)  and R 3.2.5 . Continuous data were expressed as medians [25th–75th centiles] unless otherwise specified and were compared using the Mann-Whitney test. Categorical variables, expressed as percentages, were evaluated using the chi-square or Fisher exact test. The two aims of our study were set primarily to test the feasibility of various indices of cardiac function, and to assess their physiological coherence using hierarchical clustering; this method builds homogeneous clusters based on dissimilarities or distances between cases, then proceeds iteratively to join the most similar cases. Within the same objective, we analyzed the impact of loading conditions on cardiac contractility by using bivariate correlations that were further summarized in a correlation matrix (corrplot package within R environment). Correlations were tested using Spearman’s method with Benjamini-Hochberg correction to control the false discovery rate at 0.05 level.p values < 0.05 were considered significant.Secondly, we built a focused principal component analysis  based on AMI as the dependent variable with simple graphical display of correlation structures of echocardiographic variables. Two-tailed n = 55, 82%) with cardiovascular risk factors like hypertension  and diabetes . Many patients were on long-term cardiovascular medications before hospital admission, including beta-blockers , statins , aspirin , angiotensin-converting enzyme inhibitors , angiotensin 2 receptor antagonists , and furosemide . Echocardiography examinations were performed a median of 1 [1–3] day after ICU admission and lasted a median of 21 [15–24] min/exam (not counting preparation and cleaning time). When echocardiography was ordered, 60 (90%) patients required vasopressor infusion and 66 (99%) had invasive mechanical ventilation. Overall, the feasibility of measuring echocardiographic parameters was very good, ranging from 93 to 100%  patients had at least one feature of structural cardiopathy. Briefly, seven had chronic LV hypokinesia (LVEF < 45%), ten had dilated LV, seven had concentric hypertrophy, one had eccentric hypertrophy, and one had significant heart valve disease. In addition, chronic arterial hypertension and chronic atrial fibrillation were present in 36 (54%) and 6 (9%) patients, respectively. Hierarchical clustering of echocardiographic parameters identified four coherent clusters covering the following physiological pathways: LV contractility, RV function, LV afterload, and cardiac preload Fig. a. In then = 36, 54%) prompted therapeutic changes concerning ventilator settings  or medication . Clinical and biological factors associated with 28-day mortality included older age, high SAPS II score, past medical history of arterial hypertension or chronic systolic heart failure, chronic use of some cardiovascular medications , high SOFA score and high doses of norepinephrine at time of echocardiography, lactic acidosis, and increased serum creatinine, hs-TNT, and CPK  bedside focused echocardiographic evaluation of critically ill patients with COVID-19 sepsis was feasible, safe, and incurred therapeutic changes in more than half of them; (ii) echocardiographic indices showed physiological coherence in this population where four coherent hemodynamic clusters were identified, of which two were positively correlated (LV contractility and RV function) and two others were inversely correlated (LV contractility and LV afterload); and (iii) AMI was common and inversely correlated with LV and RV contractility parameters.The high feasibility, safety, and clinical implications of echocardiography in COVID-19 septic patients suggest its usefulness in this setting as in other forms of sepsis.The feasibility of most echocardiography parameters, including strain, outweighed that previously reported, by our laboratory and others, in critically ill septic patients few years ago , 15. AltIn order to minimize the risk of infection spread among healthcare professionals , some auMost of the echocardiography examinations were followed by therapeutic changes, e.g., administering vasopressors, fluid loading, change of respiratory settings, and use of anticoagulant or thrombolysis, an incentive for a wider indication of echocardiography despite the theoretical risk of infection. A recent large global survey found a comparable impact of echocardiography on management of COVID-19 patients .We identified four coherent and homogeneous clusters involving LV contractility, RV function, LV afterload, and cardiac preload. These findings are consistent with results from previous studies highlighting the physiological coherence of echocardiographic parameters in critically ill patients with sepsis and/or acute respiratory distress syndrome , 24. TheSeveral studies in COVID-19 with or without critical illness have suggested an association between markers of RV/LV dysfunction and COVID-19 related death , 27. In n = 67); for this reason, we were not able to carry out robust multivariable analyses and could only cluster echo-parameters, but not patient groups. Some patients were assessed under ECMO, which may alter hemodynamics, but we aimed at exploring all septic critically ill COVID-19 patients, including the most severe. Another important limitation is that transthoracic (TTE) rather than transesophageal echocardiography (TEE) was used, knowing that the latter may outperform TTE for some explorations [The strengths of our study rely on the detailed phenotyping using advanced echocardiography, and the exploration of a majority of patients with critical COVID-19, unlike previous studies on the topic , 32. Ourorations . The choorations  and by tHereby, we report a comprehensive hemodynamic evaluation by echocardiography in a cohort of patients with COVID-19 sepsis. We identified four homogeneous and coherent physiological clusters. Indices of LV systolic function were positively correlated with RV function and inversely correlated with one LV afterload parameter, while no association was found with cardiac preload. AMI was common and associated with alteration of LV and RV functions. Feasibility and safety of echocardiography were good, and the test had a clinical impact on patient management in a majority of cases.Additional file 1. Complement on methods: echocardiography, Speckle tracking imaging, assessment of contractility and loading conditions and statistical analysis.Additional file 2: Fig. S1. Forest plot of odds ratios  of variables associated with day-28 mortality by univariate logistic regression.Additional file 3: Table S1. Baseline characteristics and organ failure at time of echocardiography in critically-ill patients with Coronavirus -19 sepsis, according to the need for vasopressor.Additional file 4: Table S2. Echocardiographic parameters in critically-ill patients with Coronavirus -19 sepsis according to the need for vasopressor.Additional file 5: Table S3. Association between E/A and mortality at day-28 by logistic regression after adjustment for age.


Acute mechanical circulatory support (MCS) devices are widely used in cardiogenic shock (CS) despite a lack of high-quality clinical evidence to guide their use. Multiple devices exist across a spectrum from modest to complete support, and each is associated with unique risks. In this review, we summarize existing data on complications associated with the three most widely used acute MCS platforms: the intra-aortic balloon pump (IABP), Impella systems, and veno-arterial extracorporeal membrane oxygenation (VA-ECMO). We review evidence from available randomized trials and highlight challenges comparing complication rates from case series and comparative observational studies where a lack of granular data precludes appropriate matching of patients by CS severity. We further offer a series of best practices to help shock practitioners minimize the risk of MCS-associated complications and ensure the best possible outcomes for patients. Historically, CS has been managed largely with intravenous inotropes and vasopressors, medications which improve systemic perfusion at the cost of worsening myocardial supply/demand imbalance. Despite seeming to temporarily improve hemodynamic indices and traditional markers of tissue perfusion, empiric studies have shown that escalating inotropes and vasopressors fail to meaningfully reverse the downward hemodynamic spiral that occurs in CS, with very poor survival observed in patients requiring multiple agents2.Cardiogenic shock (CS) is an advanced state of hemodynamic compromise representing a convergent endpoint of cardiac decompensation resulting from acute myocardial infarction, end-stage heart failure, myocarditis, and various other conditions. In-hospital mortality in CS remains unacceptably high, with recent estimates ranging from 27–51%3. The IABP became widely used and gained a class I indication for CS until the landmark IABP-SHOCK II trial showed that it failed to improve short- or long-term mortality in acute myocardial infarction complicated by CS (AMICS)6. Over the past decade, several other acute MCS platforms capable of providing much greater support have been developed and adopted to varying degrees in clinical practice. The trans-valvular axial flow pumps such as the Impella device  directly unload the left ventricle, capable of providing between 3 and 5.5 L/minute of flow while reducing native myocardial oxygen demand7. A percutaneous right ventricular Impella device (Impella RP) is also available, which bypasses the right ventricle by displacing blood from the right atrium to pulmonary artery8.Mechanical circulatory support (MCS) devices are commonly used to augment cardiac output and decouple systemic perfusion from native myocardial energy expenditure in CS. The intra-aortic balloon pump (IABP) was first applied in CS in the late 1960s, promising to improve hemodynamics through balloon counterpulsation synchronized with the cardiac cycle7. Because of the technical complexity and complications associated with the need for trans-septal puncture for delivery of the left atrial drainage cannula, the TandemHeart device is less commonly used in contemporary practice and thus will be only briefly discussed here. Finally, veno-arterial extracorporeal membrane oxygenation (VA-ECMO), a peripheral modification of cardiopulmonary bypass, is the only device which provides full systemic circulatory and respiratory support, though at the cost of increased left ventricular afterload9. Recognizing the futility of escalating inotropes as well as the imperative to effectively intervene before impaired systemic perfusion progresses to an irreversible state of widespread metabolic failure, we and others have proposed CS management algorithms which incorporate early application of these advanced MCS platforms, with device selection tailored to the individual patient’s hemodynamic profile13.The TandemHeart device  consists of a left atrial drainage cannula connected to an extracorporeal centrifugal flow pump, which returns blood to the descending aorta at flow rates of up to 5 L/minute14. Intravascular shear and varying degrees of hemocompatibility with non-biologic surfaces can induce hemolysis, which in combination with systemic inflammation and thromboembolism can predispose to renal failure, with significant prognostic implications15. Understanding the relative risks of these various complications with different MCS devices and their implications for device selection in patients has been extremely challenging.All MCS devices are associated with risk. This risk is increased among patients in CS who are commonly treated with vasoconstrictive agents, anticoagulants, and anti-platelet drugs, and may be exposed to other devices requiring large bore access such as hemodialysis catheters, pulmonary artery catheters, and other venous or arterial sheaths for monitoring and drug delivery. Use of large-bore MCS access along with a requirement for systemic anticoagulation increases the risk for bleeding, limb ischemia, and stroke4. Two small randomized trials comparing the TandemHeart device to IABP showed a clear signal toward higher rates of bleeding and limb ischemia with TandemHeart, though these trends were significant in only one of the two studies17. Three small, underpowered randomized trials have been conducted evaluating the use of Impella in CS. The ISAR-SHOCK (Efficacy Study of LV Assist Device to Treat Patients with Cardiogenic Shock) trial was a small study (n = 25) comparing the early generation Impella 2.5 to IABP, powered for a surrogate endpoint of hemodynamic improvement 30 minutes after device insertion18. A numerically higher incidence of bleeding, hemolysis, and limb ischemia was observed among Impella patients, though the sample was too small to evaluate the significance of these trends. The IMPRESS in Severe Shock  trial was designed to compare all-cause mortality between IABP and the Impella CP in AMICS but ended up being completed as an exploratory safety trial because of miscalculation of expected event rates19. A trend toward higher rates of bleeding and hemolysis was observed with the Impella CP, though the small sample size limited any conclusive findings. Finally, the IMPELLA-STIC trial compared IABP alone to IABP plus Impella 5.0 in 12 patients with AMICS and found a significantly higher rate of major bleeding in the combined device group, though the study was too small to evaluate the significance of other complication trends20. To date, only one randomized trial has evaluated the use of VA-ECMO in CS: the Extracorporeal Life Support in cardiogenic Shock complicating acute myocardial infarction (ECLS-SHOCK) trial randomized 42 post-arrest AMICS patients to VA-ECMO or no MCS and found similar rates of complications between groups, though again the study was underpowered for clinical outcomes including safety conclusions21.Straightforward comparison of complication rates across devices is possible only by using data from randomized trials in which equivalent patients are randomized to different device strategies. Complication rates observed in randomized trials performed to date are summarized inet al. comparing rates of stroke, bleeding, and limb ischemia among AMICS patients treated with IABP, percutaneous VADs (Impella or TandemHeart), or VA-ECMO are exemplary of these trends. In this large sample, stroke was observed in 3.1% of patients with IABP, 5.6% of those with pVADs, and 9.7% of those treated with VA-ECMO. Similarly, bleeding occurred in 19.4%, 29.9%, and 54.2% of each group, respectively, while limb ischemia occurred in 0.9%, 3.6%, and 7.7%, respectively. All of these complications were associated with increased length of stay and hospitalization costs23. While it stands to reason that more invasive devices would lead to higher complication rates, it must be noted that these observational studies do not account for significant baseline differences between the real-world patients in whom the devices are deployed. Crude insight about the severity of shock across device cohorts can be gained by comparing the short-term mortality rates in89. Two patients (4%) had major vascular events related to flow-limiting dissections of the femoral artery at device removal, with no device related mortality observed.Given the paucity of sufficiently powered randomized trials, most data on complication rates come from observational case series and registries, which are summarized inet al. performed a matched analysis comparing 237 CS patients treated with Impella in 13 European centers to 237 matched patients taken from both arms  of the IABP-SHOCK II trial24. Aminet al. identified patients undergoing PCI with MCS (linked by same-day billing data), some of whom had CS, and performed a propensity matched analysis comparing those managed with Impella with those managed by IABP25. Finally, Dhruvaet al. linked two registries to identify AMICS patients managed with Impella or IABP, matched for 75 baseline variables 26. Each study reported a higher rate of complications associated with Impella compared to IABP. Even more striking, the Amin and Dhruva studies reported a significantly higher rate of in-hospital mortality in patients treated with Impella, raising the concern that the additional complications associated with Impella may translate to higher mortality. While these analyses corroborate the trends observed in observational case series as summarized in27.A final class of studies which have been used to compare relative complication rates between devices are comparative observational analyses, which attempt to adjust for the significant baseline differences observed in cases series by attempting to match patients across available clinical variables. Three such studies have recently spurred substantial debate about complications related to Impella use. SchrageIn the absence of high-quality randomized data clarifying the net risks and benefits of MCS platforms in CS, practitioners still need to move forward and manage individual patients with CS. Recognizing that there are likely higher rates of at least some complications  with Impella and VA-ECMO compared to IABP, shock practitioners should redouble their efforts to adhere to the following best practices.11.Institutions should design structured responses (such as the ‘Shock Team’) to ensure that patients with suspected CS are rapidly identified and evaluated by qualified practitioners so that necessary resources can be urgently made available and evaluations begun regarding the likelihood of recovery or candidacy for durable MCS or transplant. Depending on the suspected inciting insult and local staffing patterns, the shock team might include interventional cardiologists, heart failure specialists, (cardiac) intensivists, and cardiac/vascular surgeons along with perfusionists and critical care nurses. Some have suggested that the cath lab be used as a default staging ground where right heart catheterization, coronary angiography, and fluoroscopic MCS insertion can all be rapidly performed12. Recent data suggest that algorithms incorporating hemodynamically guided decision-making may lead to improved survival in AMICS  to guide device selection. Just as it is important to identify the crashing patient with severe biventricular congestion who is unlikely to stabilize with IABP alone, it is equally important to identify the STEMI patient with isolated left ventricular failure well-suited for left-sided Impella, sparing them the additional complications of a more invasive device like VA-ECMO. We and others have proposed algorithms for device selection based on the ventricular congestive profile and validated indices of right ventricular function such as pulmonary artery pulsatility index (PAPi), along with the presence of concurrent respiratory failuren AMICS , though 9. We would refer readers to a comprehensive review by Subramaniam and colleagues for further discussion of risk factors and strategies to reduce complications from acute MCS devices14.Many complications can be avoided or their impact minimized if recognized and managed promptly. For example, a careful vascular assessment should be performed daily to monitor for signs of limb ischemia, which may require intervention such as external bypass or addition of a distal perfusion catheter. Similarly, markers of hemolysis should be continually tracked to assess the need for device repositioning and thorough neurologic exams performed to identify signs of stroke, which can be particularly difficult to recognize in unconscious patients. In ECMO patients, right upper extremity oxygen saturation and pulmonary capillary wedge pressure should be continuously monitored for the development of Harlequin syndrome and left ventricular distension, which may require optimization of ventilator settings, upgrade to a VAV-ECMO configuration, or addition of a left ventricular vent30.Aside from complications occurring at the time of device insertion or removal, most occur as a function of time on support. Multimodal data  should be continuously re-integrated to assess for the possibility of device weaning or the need for escalation. Specific thresholds  have been proposed to guide consideration of escalation or addition of right-sided support, though specific device algorithms will depend on local availability32. Each operator must develop these technical skills to improve outcomes.Large bore access devices above 17Fr are commonly referred to vascular surgery for removal. However, with emerging techniques, devices ranging from 12Fr to 17Fr may be removed with percutaneous closure approaches. The Perclose device (Abbott Inc) can be used at the time of device implantation (pre-closure approach) or at the time of device removal (post-closure approach) to rapidly achieve hemostasis. The Manta closure device (Teleflex Inc) has recently been introduced and may represent another approach for percutaneous vascular hemostasis. The introduction of the Impella CP with a side-arm access port allows for device removal and post-closure, thereby mitigating vascular complication risk at the time of device removalCS is a complex clinical syndrome that remains a major cause of global mortality and morbidity. MCS device utilization is growing for cardiogenic shock, though each MCS platform is associated with risks. High-quality randomized controlled trials evaluating the use of MCS devices for CS are currently lacking but are in development. Recent reports utilizing administrative datasets and retrospective registries are of limited value other than to raise awareness that randomized controlled trials are needed to improve outcomes for patients. Progress in the field will be made only when high-quality randomized trials are conducted in defined populations, powered for all-cause mortality. The decision to place an advanced device should be made by an experienced shock practitioner or team using the most complete information possible. In the meantime, clinicians should educate themselves about hemodynamically driven decision-making algorithms and best practices to reduce complications associated with each MCS platform.


Right ventricular outflow tract continuity abnormalities are one of the most commonly encountered entities in the field of congenital cardiac surgery. Various strategies including homograft, valve conduit, Contegra are used to restore continuity between right ventricle and pulmonary artery. In countries like Pakistan these may not be easily available and affordable. We report the experience of our short observational study of using a handmade trileaflet valve conduit to reconstruct the right ventricular outflow tract.From September 2015 to December 2016, a total of 15 patients with different congenital heart diseases underwent open-heart surgery at our institute. Restoration of right ventricular to pulmonary artery continuity was achieved using handmade valve conduit utilizing bovine pericardium and thin sheet PTFE sheets (0.1 mm) as conduit and valve respectively.Patients ranged from 1 to 16 years. Seven patients had previous palliation including 4 blalock taussig (BT) Shunts and 3 pulmonary artery (PA) banding. Postoperative complications were observed in 4 patient including 2 in hospital deaths and 2 required interventions. One patient developed aneurysm at RV- conduit junction requiring surgical repair and the other underwent conduit dilatation for moderate to severe stenosis (gradient 60 mmHg). No significant regurgitation was observed in this series. Overall postoperative gradients were stable with mean gradient 25.3 mmHg (8 mmhg - 60 mmHg).The use of handmade valve conduits has acceptable morbidity and mortality. These are cost effective alternatives in this part of the world, where well-established conduits have cost implications and uncertain availability. •Reconstruction of Right ventricular to Outflow tract is challenging surgically.•Right ventricular outflow tract reconstruction using bovine pericardium and PTFE graft is cost effective•Right Ventricular outflow tract reconstruction using bovine pericardium and PTFE has reasonable outcome. Right v2This is a retrospective descriptive study. The study is conducted at the Aga Khan University Hospital; it is a multidisciplinary tertiary care hospital. All those patients where hand made trileaflet valve conduit was constructed and used are included. The patients receiving synthetic valve conduit or contegra (bovine jugular vein) were excluded. From September 2015 to December 2016, a total of 15 consecutive patients with different congenital heart disease diagnosed in the pediatric age group (up to 16 years) at our institute, the Aga Khan University Hospital underwent open-heart surgery with restoration of RV to PA continuity by using handmade valve conduit. The size of the conduit was determined by using an available nomogram. The data was collected from medical records regarding the demography, past medical history, surgical management and postoperative follow ups. The confidentiality and anonymity of the participants is ensured. The data was collected through charts and kept confidential and available only to the research participants.2.1All the procedures were performed by the same group of experienced and qualified surgeons. The two surgical teams worked simultaneously with one team operating on the patient and the other helped in fashioning of the valve conduit so as to reduce the overall operating time. The valve conduit was constructed according to the nomogram as determined by the size of the patient. The bovine pericardium and thin sheet PTFE sheets (0.1 mm) were used to construct conduit and valve respectively . The ope3A total of 15 patients underwent handmade trileaflet PTFE valve conduit right ventricular outflow tract reconstruction from 2015 to 2016. Age range from 1 to 16 year. Overall postoperative gradients were stable with mean gradient 25.3 mmhg (8 mmhg – 60 mmhg) . All the4The idea of using a valve conduit for better hemodynamic performance has made it possible to treat several complex congenital disorders that would not have been possible otherwise . Use of Homografts were the initial valve conduit used for reconstruction of the right ventricular outflow tract and was first reported for pulmonary atresia in 1966 . It's thDue to early graft failure of homograft, porcine heterografts mounted in Dacron conduits became available in a variety of sizes and were widely used for complex reconstructions . The resThe lack of small-size homograft availability, overall scarcity and the concerns about their long-term outcome  have ledMortality has never been a consideration related to restoration of RV to PA continuity with a conduit and the studies suggest that the use of contegra or other types of valve conduits were not directly contributing to early deaths as no technical problem related to conduit placement was identified and in fact, even on autopsy anatomical integrity was intact ,22. We aDespite advances in surgical technique and new conduit types, most RV-PA conduits will require revision in due time. Thus, patients who survive to adulthood face the prospect of >1 conduit replacement in their lifetimes .The requirement of redo surgery with cost implications and unavailability of majority of conduit has led to development of right ventricular outflow tract reconstruction by using a PTFE sheet (of various thicknesses). The PTFE sheets for leaflet reconstruction are inexpensive and easily available. It has unique property of very low tissue affinity. Because of this property, cellular or fibrinous deposition is unlikely, and for these reasons, it is the most reliable material for small-caliber vascular grafts . Also beIn a country like Pakistan where cost is an extremely important prohibitive factor in carrying out such complex procedures where valve conduits are required and repeated procedures are anticipated, leading to immense financial burden on health care. We have started constructing handmade trileaflet valve conduit in the operating room using bovine pericardium and a PTFE sheet according to the size of the patient using a nomogram established for this purpose , Fig. 2.Our Result of handmade valve conduit were encouraging and for developing countries like Pakistan where there is unavailability of majority of conduit and cost issue for homograft, Contegra (2500 $) and synthetic valve conduit, Handmade trileaft PTFE valve conduit (700$) is cost effective and excellent alternative with desirable result.The study is limited by the fact that number of patient is too small to justify statistical testing for a meaningful significance. The other limitations are the retrospective nature of study and that only short term results are reported. The strength of this modest study is that this will guide to resolve the problems associated with excessive cost and the lack of availability of homograft, synthetic graft and contegra. The technique of reconstruction is simple and reproducible and the material used is cost effective and has much better availability in this region.5Handmade trileaflet valve conduit using bovine pericardium and PTFE provides reliable alternative for RVOT reconstruction yielding to its cost effectiveness and easy availability especially in developing countries with good short term outcome.None.Department exemption taken.Yasir Khan: Data collection, manuscript writing, statistical analysisSyed Shahab: Statistical Analysis, Manuscript editing.Muneer Amanullah: final analysis.1. Name of the registry: Research Registry.2. Unique Identifying number or registration ID: researchregistry5703.https://www.researchregistry.com/browse-the-registry#home/.3. Hyperlink to your specific registration (must be publicly accessible and will be checked): : Syed ShahabAssistant Prof, Cardiac SurgeryAga Khan University Hospital Karachi, Pakistan.Informed consent taken from all patients.Not commissioned, externally peer reviewed.


To assess the global and regional right ventricular (RV) deformation in hypertrophic cardiomyopathy (HCM) patients with preserved right ventricular ejection fraction (RVEF) using 3.0-T cardiovascular magnetic resonance tissue tracking (CMR-TT). Eighty-two HCM patients and 32 age- and sex-matched healthy controls were enrolled. HCM patients were divided into groups depending on the presence or absence of right ventricular hypertrophy (RVH), RV late gadolinium enhancement (RV-LGE), and left ventricular outflow tract obstruction (LVOTO), respectively. The RV global and apical longitudinal peak strain (LPS) in HCM patients with RVH were significantly lower than that in HCM patients without RVH and controls (P < 0.05). The global, apical and mid-ventricular LPS in HCM patients with RV-LGE were significantly lower than that in HCM patients without RV-LGE and controls (P < 0.05). Lower LPS was demonstrated in HCM patients without RV-LGE compared with controls in apical and mid-ventricular levels (P < 0.05). No significant difference was found regarding global and regional LPS in HCM patients with LVOTO compared without LVOTO . CMR-TT was able to detect subclinical RV myocardial deformation prior to RVEF impairment, which was more severe in the presence of RVH and RV-LGE. It is also one of the most common causes of sudden cardiac death in young individuals and athletes4. In previous studies, increased right ventricular (RV) wall thickness and RV dysfunction in patients with HCM were shown to predict severe symptomatic HCM and poor prognosis6. RV ejection fraction (RVEF) has been typically used to assess the RV systolic function and has been shown to predict clinical outcomes of patients with cardiomyopathy7. However, the RVEF of patients with HCM tends to be within the “normal” range8. Currently, RV strain parameters are considered as more valuable markers of myocardium dysfunction than RVEF. RV strain parameters have been used for prognostic evaluation of multiple cardiovascular diseases and RV deformation in the healthy population13. The global and regional RV deformation in HCM patients with preserved RVEF is not well characterized18.Hypertrophic cardiomyopathy (HCM) is a primary and genetically transmitted cardiovascular disease with a prevalence of 1:500 in the general population. The condition is associated with a risk of adverse cardiac events such as severe arrhythmias, progressive heart failure, and sudden cardiac death19. CMR tissue tracking (TT) technology is a non-invasive method to assess myocardial deformation without the use of contrast media. Previous studies have applied CMR-TT technique with good intra- and inter-observer variability for determining the global and regional left ventricular (LV) deformation in the early stages of HCM21. However, to the best of our knowledge, information pertaining to RV strain in patients with HCM by CMR-TT is limited. Therefore, the aim of this study was to determine the global and regional RV deformation in patients with HCM with preserved RVEF by using CMR-TT.Cardiovascular magnetic resonance (CMR) is the standard reference modality for evaluation of RV structure and functionP = 0.087). Maximum RV free wall thickness in HCM patients was significantly greater than that in controls .The basic characteristics of the study population were shown in Supplementary Table th, 75th percentile): −6.45% [−10.78%–(−3.49%)] vs. −9.54% ± 3.60%, P < 0.05], apical LPS [median : −8.56% [−11.99%–(−5.97%)] vs. −13.14% [−15.65%–(−9.98%)], P < 0.05], and mid-ventricular LPS [median : −5.83% [−10.91%–(−6.22%)] vs. −11.01% [−13.35%–(−5.94%)], P < 0.05] were significantly lower than those in controls (Table P > 0.05); however, the apical CPS, mid-ventricular CPS, and basal RPS in HCM patients were significantly lower as compared with controls (P < 0.05).In patients with HCM, the global LPS . Of the HCM patients with RVH, 19(59%) had apical RVH; 18(56%) had mid-ventricular RVH and 5(16%) had basal RVH. The global RV longitudinal peak strain (LPS) [median : −4.70% (−6.47%–1.74%) vs. −8.31% [−12.00%–(−5.58%)], −4.70% (−6.47%–1.74%) vs. −9.54% ± 3.60%, P < 0.05, respectively] and apical LPS [median : −7.21% [−9.62%–(−3.74%)] vs. −9.26% [−14.74%–(−6.48%)], −7.21% [−9.62%–(−3.74%)] vs. −13.14% [−15.65%–(−9.98%)], P < 0.05, respectively] in HCM patients with RVH were significantly lower than those in HCM patients without RVH and controls. Patients with RVH showed a tendency for lower mid-ventricular LPS as compared to controls (P < 0.05). The basal RV LPS in HCM patients with RVH was significantly lower than that in HCM patients without RVH (P < 0.05). There were no differences of the global and regional CPS and RPS between HCM patients with RVH and HCM patients without RVH (P > 0.05) : −2.99% (−5.50%–6.80%) vs. −7.60% [−11.48%–(−4.88%)], −2.99% (−5.50%–6.80%) vs. −9.54% ± 3.60%, P < 0.05, respectively], apical LPS [median : −6.97% (−8.15%–1.98%) vs. −9.05% [−13.53%–(−6.23%)], −6.97% (−8.15%–1.98%) vs. −13.14% [−15.65%–(−9.98%)], P < 0.05, respectively] and mid-ventricular LPS , P < 0.05, respectively] in HCM patients with RV-LGE were significantly reduced compared with HCM patients without RV-LGE and controls. There was no significant difference between HCM patients with and without RV-LGE with respect to global and regional CPS as well as RPS (P > 0.05)  had the apical RV-LGE, 10 (77%) had middle ventricular RV-LGE, while only 1(8%) showed at the RV basal region. The global RV LPS  and inter-observer  reproducibility. Global CPS showed moderate intra-  and inter-observer  agreement. The inter-observer ICC of global RPS was 0.864, while the intra-observer ICC was 0.875 (Table The main findings of our study were as follows: 1) Global and regional RV LPS strain in HCM patients with RVH were lower than those in HCM patients without RVH. 2) Global and regional RV LPS in individuals with RV-LGE were lower than those in controls. 3) There were no significant differences with respect to RV strain between HCM patients with LVOTO and those without LVOTO. CMR-TT has the capability to quantitatively assess the global and regional RV myocardial strain in HCM patients with preserved RVEF with high reproducibility in longitudinal direction.20. It precludes the use of complex post-processing procedure in CMR tagging technology22; in addition, the intra-observer reproducibility of CMR-TT strain analysis is independent of magnetic field intensity23. In this study, we observed good inter- and intra-observer reproducibility for global LPS and CPS in HCM patients, which is consistent with previous studies21.RV strain parameters are typically regarded as markers of myocardial deformation and can be measured by many CMR myocardial tracking technologies. CMR-TT makes use of the near incompressibility of the myocardium and allows for the assessment of myocardial deformation by tracking both endocardial and epicardial boundary voxels18. In this study, we found increased maximum RVFWT in all HCM patients, which is consistent with previous studies18. This phenomenon may be attributable to a combination of genetic mutation that encodes sarcomere proteins, variation of afterload, or ventricular interdependence; however, further studies are required to elucidate the main trigger mechanism24. Moreover, previous studies demonstrated that RV deformation is important to assess the outcomes of patients with HCM25. Most previous studies have focused on LV changes in HCM patients, while few studies have characterized RV deformation in HCM patients using CMR. We found that global and regional RV LPS were impaired and RV CPS was regionally decreased in all HCM patients with preserved RVEF. Further, global RV LPS in HCM patients with preserved RVH was lower than that in patients without RVH and control subjects. In our study, impaired regional myocardial deformation mainly occurred at the apical and mid-ventricular levels and the basal myocardial deformation was not decreased compared with controls. This was corresponding to the location of RVH in HCM patients we found. Previous study about the analysis of LV strain has shown that the myocardial deformation of hypertrophic region was more impaired than nonhypertrophic region21. The mode of our group and found were similar to their study. We conjectured that the hypertrophy and disarray of myocardial cell in RV may have caused changes in RV deformation and kinetic feature.RV wall thickness has been shown to be a common structural RV abnormality in HCM patients26. In our study, RV-LGE was also observed in HCM patients, which suggested that the RV of HCM patients may be affected by myocardial fibrosis. HCM patients with RV-LGE had lower values of global and regional LPS compared with patients without RV-LGE and controls; these findings also supported that fibrosis might lead to myocardial dysfunction. In addition, the location of RV-LGE was similar to that of RVH, i.e., largely confined to the intersection areas of two ventricles at the apical and mid-ventricular levels; this suggested that the pathologic changes in RV were broadly similar to those in the LV27. The presence of RV-LGE may have some clinical value in the prognostic assessment of HCM patients; however, further studies are required to obtain more definitive evidence.The presence of LGE in LV has always been considered as indicative of myocardial fibrosis and a prognostic marker in HCM patients2. Previous studies have shown that patients with HCM who have LVOTO are at a higher risk of sudden cardiac death or progression to severe congestive symptoms29. Studies have also shown that inter-ventricular septum is shared by two chambers and that the LV motion may affect RV motion by direct mechanical interaction6. However, we observed no significant differences in RV strains between HCM patients with LVOTO and those without LVOTO, which is consistent with previous studies14. These findings suggest that LV hemodynamic changes induced by LVOTO may have little impact on RV deformation in patients with preserved RVEF.Increase in the left ventricular out flow gradient is an important marker of development of LVOTO in patients with HCM30. The quantitative data of myocardial strain using different software might be different, thus more work is required to determine the normal reference values of global and regional 3D RV strain. Finally, genetic-test and follow-up data which unavailable for this study should be acquired to assess the clinical relevance of RV strain parameters as prognostic markers in HCM patients in our further studies.Our study has the following limitations. Firstly, this was a single-center retrospective study; multicenter study with a larger cohort is required to confirm our findings. Secondly, the normal reference values of global and regional 3D RV strain by CMR TT are not well determined, but our results were similar to our team’s previous articleTo summarize, in this study, decreased global and regional RV myocardial strain were detected prior to the reduction in RVEF, which suggests subclinical impairment of RV strain in HCM patients compared with controls. Moreover, impaired RV myocardial deformation was more obvious in the presence of RVH and RV-LGE. The location of impaired regional RV strain was mainly confined to the apical and mid-ventricular region, which was consistent with the locations of RVH and RV-LGE. Although the two ventricular chambers show interdependence and LVOTO can lead to LV hemodynamic abnormality, LVOTO may play a limited role in RV deformation in HCM patients with preserved RVEF.3. Preserved RVEF was defined as RVEF ≥ 45% in this study18. Patients who presented with any of the following conditions were excluded: hypertension (n = 53), severe coronary artery disease (n = 11), previous treatment such as myomectomy or ablation (n = 7), or poor or false CMR images (n = 18). Finally, 82 patients with HCM  with preserved RVEF were enrolled. Patients were divided into groups depending on the presence (n = 32) or absence (n = 50) of right ventricular hypertrophy (RVH), on presence (n = 13) or absence (n = 69) of late gadolinium enhancement in RV (RV-LGE), and on presence (n = 54) or absence (n = 28) of left ventricular outflow tract obstruction (LVOTO). RVH was defined as RV maximum thickness at the end of diastole more than 5 mm as measured by CMR32. LVOTO was defined as peak LV outflow tract pressure gradient ≥30 mmHg, as measured by echocardiography3.In this retrospective study, we recruited 169 patients who were diagnosed with HCM (according to the criteria recommended by the ACCF/AHA and ESC guidelines) between January 2010 and January 2018 at our institution33. Written informed consent was obtained from all patients and controls.In this study, 32 age- and sex-matched healthy individuals were enrolled as the control group . The exclusion criteria for controls were: chronic disease, family history of cardiovascular disease, hypertension (blood pressure > 140/90 mmHg), or severe arrhythmias. This study was approved by the Institutional Ethics Review Board of West China Hospital and performed in accordance with the ethical guidelines of the Declaration of Helsinki (2013 EDITION)2; slice thickness = 8.0 mm; matrix size = 200 × 256. Fifteen minutes after intravenous injection of 0.2 ml/kg gadolinium chelate contrast agent (Gadobenate dimeglumine (MultiHance), 0.5 mmol/ml; Bracco, Milan, Italy), late gadolinium enhancement (LGE) images were acquired using the phase-sensitive inversion recovery (PSIR) sequence .The CMR images were acquired using a 3.0-T CMR scanner  with body phased array coil. All subjects assumed the supine position and remained stable during the entire process. Electrocardiogram (ECG) and breathing were monitored by the manufacturer’s standard ECG-triggering device and the end-expiratory breath-holding technique. All images were obtained during the breath-holding period. Vertical 2-chamber long axis, horizontal 4-chamber long axis, and 8-12 contiguous short-axis cine series from the base to the apex level were acquired using a Turbo FLASH sequence. The typical sequence parameters were: repetition time (TR) = 47.88 ms; echo time (TE) = 1.51 ms; flip angle = 40°; field of view (FOV) = 265 × 340 mmAll CMR data were analyzed off-line by an experienced radiologist (three years of experience in CMR) using commercially available software . In each short-axial cine dataset, we delineated the optimal endocardial and epicardial borders of both ventricles at the end-diastolic and end-systolic phase and defined the insertion of RV and LV as the reference point. The ventricular extent was defined as extending from the bicuspid or tricuspid valve to the apex in the horizontal 4-chamber long axis view. Papillary muscles, and moderator bands were diligently excluded. Global cardiac structural parameters, including biventricular ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and diastolic cardiac mass, and the maximum LV end-diastolic thickness (EDTH) were generated automatically by the cvi42 short−3D module of the software. Maximal RV free wall thickness (RVFWT) was measured manually from images of end-diastolic phase. The RV-LGE was a qualitative parameter and determined by two experienced radiologists in a blinded manner  deformable myocardial model . Categorical data are presented as frequencies and percentages. Man-Whitney U test or Student’s t test was used to compare biventricular function parameters between HCM patients and controls. Fisher exact test was used to assess differences between male and female patients; differences of global and regional myocardial peak strains between groups of patients and controls were assessed with the Kruskal–Wallis test. Intra- and inter-observer variability with respect to RV peak strain was assessed using intraclass correlation coefficient (ICC). Two-tailed P values less than 0.05 were considered statistically significant.Statistical analysis was performed using IBM SPSS  and MedCalc . Continuous variables are expressed as mean ± standard deviation (SD) or as median (25Supplementary information.


In conclusion, RV ECV can be assessed if image quality allows sufficient distinction between myocardium and blood, and RV wall thickness per ROI is ≥ 1 pixel. T1 maps in SAX are recommended for RV ECV analysis. LOI application simplifies RV ECV measurements.The right ventricle´s (RV) characteristics—thin walls and trabeculation—make it challenging to evaluate extracellular volume (ECV). We aimed to assess the feasibility of RV ECV measurements in congenital heart disease (CHD), and to introduce a novel ECV analysis tool. Patients (n = 39) and healthy controls (n = 17) underwent cardiovascular magnetic resonance T1 mapping in midventricular short axis (SAX) and transverse orientation (TRANS). Regions of interest (ROIs) were evaluated with regard to image quality and maximum RV wall thickness per ROI in pixels. ECV from plane ROIs was compared with values obtained with a custom-made tool that derives the mean T1 values from a “line of interest” (LOI) centered in the RV wall. In CHD, average image quality was good , and RV wall thickness was 1–2 pixels. RV ECV was not quantifiable in 4/39 patients due to insufficient contrast or wall thickness < 1 pixel. RV myocardium tended to be more clearly delineated in SAX than TRANS. ECV from ROIs and corresponding LOIs correlated strongly in both directions (SAX/TRANS: r = 0.97/0.87,  Both focal5 and diffuse myocardial fibrosis11 have been described in different forms of CHD using cardiovascular magnetic resonance (CMR). This fibrosis is associated with decreased exercise capacity, ventricular dysfunction, and arrhythmia. CMR T1 mapping is a non-invasive tool to quantify diffuse myocardial fibrosis. The expansion of the interstitium as a marker for fibrosis can be assessed by measuring the myocardial volume of distribution of gadolinium-based contrast agents 12.Myocardial fibrosis contributes to the development of heart failure in adult congenital heart disease (CHD)8, yet data on myocardial ECV of the RV are limited13. The thin wall and distinct trabeculation of the RV complicate the differentiation between blood and myocardium required for accurate ECV determination. Conventional planimetric region of interest (ROI) analysis is regarded as the standard approach for ECV analysis in the LV14, but it is cumbersome and time-consuming for small, thin structures such as the RV. In these situations, a displacement of the outer border of the ROI by 1 pixel can already significantly affect the average value of the ROI, and thus the results of ECV calculations. We developed a tool that does not require contouring of the RV wall. Instead, the RV wall is directly targeted in its center as a “line of interest” (LOI), without the necessity for delineating between myocardial and blood pixels, and thus facilitating a quick and simple evaluation of myocardial RV ECV.While management of acquired heart diseases is focused on the left ventricle (LV), in CHD it is frequently the right ventricle (RV) that is affected by the underlying disease. Significantly elevated levels of myocardial LV ECV derived from CMR have been found in mainly right ventricular congenital pathologies as tetralogy of Fallot (TOF)The present study aimed a) to evaluate the feasibility of CMR-based measurements of RV ECV with T1 mapping in patients with CHD, and b) to introduce the novel LOI approach in comparison with conventional planimetric ROI analysis.Consecutive patients ≥ 14 years of age with CHD referred for clinical CMR were prospectively recruited for the study. Exclusion criteria were significant renal impairment, chronic or acute infection up to four weeks prior to CMR, non-magnetic resonance imaging compatible devices, claustrophobia, and defective datasets or missing hematocrit values. The control group consisted of healthy young adults > 18 years with no previous history or symptoms of cardiovascular disease, no kidney dysfunction, normal 12-lead electrocardiogram and blood pressure, and no contraindications to perform CMR. Controls underwent CMR only for study purposes, additional examination of any other organ was not performed.The study was approved by the institutional ethics committee (Charité – Universitätsmedizin Berlin) following the ethical guidelines of the 1964 Declaration of Helsinki and its later amendments. All participants and guardians of individuals < 18 years gave written informed consent to participate in the study.After exclusion of two patients and two controls with defective datasets and missing hematocrit values, a total of 39 CHD patients and 17 controls were available for further analysis.15. Sequence parameters were: MOLLI scheme 3b(3b)3b(3b)5b, repetition time 2.4 ms, echo time 1.2 ms; flip angle 35°, slice thickness 8.0 mm. Images were acquired in a single midventricular plane in SAX and transverse orientation (TRANS) before and 15 min after bolus application of gadoterate meglumine  or gadopentetate dimeglumine  at a dose of 0.1 mmol/kg16.Subjects were studied using a clinical whole-body 1.5 T MR imaging system . T1 mapping was performed with an optimized ECG-gated single-shot modified Look-Locker inversion-recovery (MOLLI) sequence17. T1 maps generated from the corrected T1 images were stored as DICOM files, and T1 data analyzed with the open-source software OsiriX18.The open-source image reconstruction tool MRmap, run with IDL Virtual Machine version 8.3 , was applied to generate T1 maps after manual correction for body motion. With the help of a grid structure superimposed onto the T1 source images to allow visual registration, images sorted by inversion time were separately displaced in x or y direction to correct for misregistrationBlood T1 was obtained from regions of interest (ROIs) delineated in the blood pool of the systemic (subaortic) ventricle. Myocardial ROIs with a minimum length of 10 mm were drawn in the LV wall  in SAX, and in the thickest, non-trabeculated part of the free, inferior or anterior wall of the RV in SAX and TRANS. ROIs were placed accurately in the myocardium to minimize partial voluming with adjacent blood or extramyocardial tissues. RV ROIs were evaluated with regard to image quality Table  and maxiIn addition to planimetric ECV analysis, RV ECV was determined with a novel centerline approach Fig. . A curve20:Hematocrit values were gained immediately before CMR to calculate ECV as followsImage analysis was undertaken by a single operator with 7 years of experience in CMR imaging in CHD. To test intraobserver variability of T1/ECV measurements, the same operator repeated the analysis in a subset of 10 randomly chosen CHD patients and 5 controls at least 2 weeks apart from the first time of measurements. For interobserver variability, a second observer with 5 years of experience in CMR, blinded to the clinical diagnosis and to other CMR results, performed image analysis in the same subset of patients.t test or Mann–Whitney U test. Intra- and interobserver variability were tested with Bland–Altman analysis and correlation coefficients. Statistical analyses were performed with SPSS version 24.0 . A p value < 0.05 was considered statistically significant.Normality was assessed with the Shapiro–Wilk test. Values are expressed as median (range), mean ± SD, or numbers (n) and percentages (%), as appropriate. Associations between continuous variables were assessed with Pearson´s or Spearman´s correlation coefficients (r). Bland–Altman analysis was applied to compare RV ECV from SAX and TRANS, and ECV from plane ROIs and corresponding LOIs within groups. Comparisons between patients and controls were performed with unpaired p = 0.310) and gender distribution (p = 0.640).In total, 39 CHD patients and 17 controls were analyzed. Patient demographics and diagnoses are summarized in Table p < 0.001) and ECV . Bland–Altman analysis showed no significant bias in native T1 or ECV between the different orientations. ECV could not be determined in SAX in 6/39 patients due to insufficient image quality (n = 2) or RV wall thickness (n = 4). In 14/39 patients, ECV analysis in TRANS was not possible because image quality was too low  and ECV , without significant bias in the Bland–Altman analysis. RV ECV measurements were not possible in SAX in 9/17 and in TRANS in 12/17 control subjects as RV walls were too thin to accurately delineate myocardium from extramyocardial tissues. In 1/9 without SAX values, ECV was available in TRANS.In the control group, correlation between SAX and TRANS was strong for RV native T1 . Significant differences in native T1 of RV and LV between patients and controls were not observed . In patients, native T1 and ECV of the RV in systemic vs. subpulmonary position were not significantly different . RV native T1 and ECV did not correlate with RV end-diastolic volume index , end-systolic volume index  or ejection fraction . An association with RV wall thickness per ROI in pixels was not seen .RV ECV and LV ECV from SAX were significantly higher in CHD patients than in controls . The distribution of scores is shown in Table Image quality was high in patients and controls , and tended to be higher before than after contrast application . Maximum RV wall thickness per ROI was greater in CHD  than in controls  had insufficient image quality (score grade 3), and three patients ; right pulmonary artery stenosis) had minor RV wall thickness per ROI . In 8/17 controls, RV wall thickness was insufficient for RV ECV analysis.p < 0.001) and TRANS . With regard to RV ECV, correlation was very strong between values derived from ROI and LOI s in SAX . Bland–Altman analysis revealed no significant bias between the two methods. An overview of RV native T1 and ECV values is given in Table RV native T1 from ROI agreed well with values from corresponding LOIs across health and CHD in SAX  and strong for LV ECV .In a subset of patients with repaired TOF (n = 10), the LOI method was compared with ROI for T1 measurements of the LV. Agreement between ROI and LOI was moderate for native T1  in patients with pulmonary hypertension. In that cohort, RV ECV was significantly higher than in healthy volunteers and patients with heart failure and reduced LV ejection fraction but without pulmonary hypertension24.In children post Fontan palliation with a systemic RV, increased markers of diffuse myocardial fibrosis negatively correlated with strain parameters from CMR feature tracking, suggesting an association with decreased myocardial contractility25. In our study, RV ECV from SAX and TRANS correlated strongly in patients and controls. However, the RV myocardium tended to be more clearly delineated in SAX, resulting in a higher number of measurable T1 data sets, and thus suggesting a more reliable measurability of RV ECV. We would therefore recommend T1 maps in SAX for RV analysis. In individual subjects, T1 images in TRANS may additionally be acquired as a potentially useful alternative if ROIs cannot accurately be placed in the RV myocardium in SAX.For RV volumetric analysis, cine imaging in transverse  plane has been recommended, as it allows for better recognition of the anatomic landmarks of the RV and improved visual assessment of RV longitudinal contractility, in turn leading to more reproducible measurements of RV volumesRV ECV from plane ROIs agreed well with values from corresponding LOIs. To account for the fact that the ROI method has not yet been validated for ECV measurements of the RV, LOI was compared with ROI as the “gold standard” for T1 analysis of the LV. In line with the RV, correlation between LV ECV values from ROI and LOI was strong. Instead of contouring the myocardium, the centerline approach targets the ventricular wall directly in its center without the need for differentiation between myocardial and blood pixels. The application of this custom-made tool facilitates a quick and simple evaluation of myocardial RV ECV, and thus may support the integration of ECV measurements into clinical CMR workflows. Furthermore, this approach may in the future also prove to be useful for the assessment of other thin cardiac structures, e.g. atrial walls or thin LV myocardium in dilated cardiomyopathy.26. In our study, both native T1 and ECV correlated similarly between T1 map orientations and measurement methods, while significant differences between patients and controls were only seen with regard to ECV. Especially in patients with CHD and the need for serial CMR examinations, a non-contrast approach would be favorable. Furthermore, T1 mapping of the RV can particularly be challenging after contrast, as underlined by the lower image quality of post-contrast T1 maps seen in this study. Whether native T1 is a reliable marker of myocardial disease in CHD remains to be proven.In addition to ECV, native T1 is a commonly applied T1 mapping metric to evaluate myocardial fibrosis. In patients with cardiomyopathy, native T1 provided the greatest distinction between healthy and diseased myocardium compared to post-contrast T1 and ECV28, further research is required to assess the potential of non-invasive T1 mapping parameters within the clinical management of CHD.Given the key role of diffuse myocardial fibrosis within the multi-causal development of heart failure and the possible efficacy of antifibrotic treatment29, hypertrophic12, and dilated cardiomyopathy30, while RV ECV yet needs to be validated. Although particular care was taken when drawing a ROI into the RV myocardium at a minimum wall thickness of > 1 pixel, partial voluming with blood or fat due the thin myocardium and trabeculation of the RV could potentially have led to an overestimation of ECV, in turn limiting the accuracy of RV ECV measurements. It has been shown that LV ECV values are reproducible across CMR scans31. Since serial CMR examinations were not performed in the present study, test–retest reliability of RV ECV measurements could not be analyzed.The present study has several limitations. The patient cohort is relatively small and heterogeneous, making it difficult to draw specific conclusions relating to the higher ECV but similar native T1 values when compared to the healthy controls. Given the age of the study population, results should be confirmed in pediatric cohorts with younger CHD patients taking into account potential spatial and temporal resolution issues. Histological validation of ECV was not performed since biopsy and/or surgery was not clinically indicated in any of the enrolled patients. Previous studies have shown good agreement between LV ECV from T1 mapping and collagen volume fraction from myocardial biopsy in aortic stenosisIn conclusion, our study demonstrated that non-invasive evaluation of RV ECV by CMR T1 mapping is feasible in CHD provided that image quality allows for sufficient distinction between myocardium and blood, and that RV wall thickness per ROI is ≥ 1 pixel. Furthermore, the application of a manually drawn LOI centered in the RV myocardium simplifies RV ECV analysis. Future studies are necessary to further explore the potential role of myocardial ECV as a non-invasive marker for prognosis, risk stratification, and monitoring of disease and therapy in CHD.


To study the associations between fatty liver (FL), insulin resistance, myocardial high-energy-phosphate (HEP) and glucose metabolism, and heart function in patients with uncomplicated type 2 diabetes mellitus (T2DM).1H-MRS of the liver for the assessment of liver fat, myocardial 31P-MRS for assessment of myocardial HEP metabolism and MRI to determine left ventricular function were performed. Furthermore, a hyperinsulinemic, euglycemic clamp was performed to establish whole body insulin sensitivity. Moreover, PET with H215O (fasting conditions) and [18F]-2-fluoro-2-deoxy-D-glucose (clamp conditions) were used to determine myocardial blood flow (MBF) and myocardial metabolic rate of glucose uptake (MMRglu) in a subgroup of 28 patients.We studied 35 T2DM patients (Mean ± SD Hba1c = 7.0 ± 0.8%) without coronary artery disease or heart failure, as determined by echocardiography. 2, p < 0.05), reduced whole body insulin sensitivity (0.45 ± 0.48 vs 0.74 ± 0.44 (mg/kg·min)/(pmol/L), p < 0.05), and reduced MMRglu , as compared with patients without FL, while MBF was not different. The ratio of phosphocreatine over adenosine triphosphate, a marker of myocardial HEP metabolism, was reduced in patients with FL , also after adjustment for BMI, and correlated to MMRglu . LV systolic and diastolic function were not statistically significantly different. Figure 1Patients with FL  showed increased body mass index (29.5 ± 3.2 vs 27.2 ± 2.8 kg/mFatty liver in patients with uncomplicated T2DM is associated with decreased myocardial HEP metabolism. In addition myocardial HEP metabolism is modulated by myocardial glucose uptake.