Low physical activity (PA) level and high sedentary time (SED) have been associated to cardiovascular (CVD) morbidity and mortality. Routinely assessing the PA-level of patients being admitted to hospital has been proposed. The aim was to explore PA-level and SED among patients prior to cardiac ward admission and whether this can predict all-cause mortality.A longitudinal observational study of patients with ischemic heart disease, heart failure, cardiac arrhythmia, valvular heart disorder and inflammatory heart diseases treated on cardiac wards (2015-2016) in Stockholm, Sweden. Data on PA-levels and SED prior to admission were collected by validated questionnaires during inpatient care. PA level a regular week was calculated by an index (3-19 points) including everyday PA and exercise. The cut-off of insufficiently physically active was set to > 9 points. Individuals' reporting ≥7 hours of sitting a normal day were categorised as high SED. Differences in PA-level and SED between different diagnose groups were explored by Benjamini-Hochberg procedure. The associations between PA-level and SED with all-cause mortality were analysed using cox regressions, adjusting for age, sex, diagnosis group, education level, disposable income, smoking status, alcohol consumption and eating habits.Among 1148 patients with CVD, approximately 56% were considered as insufficiently physically active (>9 points). In addition, approximately half the study population were categorized as high SED (≥7 hours per day). There were differences in PA-level and SED between the various cardiovascular diagnoses, with individuals with heart failure and valvular heart disorder being in general more inactive and having higher levels of SED. A total of 200 deaths occurred during a median follow-up time of 2.6 years. The mortality was higher among those categorised as insufficiently physically active  or high SED  compared to those reporting sufficient PA and low SED, respectively.A high amount reported insufficient PA and a high amount of SED preceding hospitalisation. There was an association between PA (negatively) and SED (positively) with all-cause mortality among patients with CVD. This highlights the prognostic value of assessing patients' PA-level and SED in clinical practice.


Ventricular septal flattening reflects RV pressure overload in pulmonary arterial hypertension. Eccentricity index (EI) and pulmonary artery distensibility (PAD) correlate with pulmonary artery pressure. We assessed the utility of these using cardiac magnetic resonance (CMR) to assess for pulmonary hypertension (PH) in patients with chronic thromboembolic disease. This may allow non-invasive differentiation between patients who have chronic thromboembolic pulmonary hypertension (CTEPH) and those with pulmonary vascular obstructions without PH at rest, known as chronic thromboembolic pulmonary disease (CTEPD).Twenty patients without resting pulmonary hypertension, including ten with chronic thromboembolic disease, and thirty patients with CTEPH were identified from a database at the Scottish Pulmonary Vascular Unit. CMR and right heart catheter had been performed within 96 h of each other. Short-axis views at the level of papillary muscles were used to assess the EI at end-systole and diastole. Pulmonary artery distensibility was calculated using velocity-encoded images attained perpendicular to the main trunk.p ≤ 0.01 and  and compared to those with CTED. PAD was significantly lower in CTEPH compared to controls  and compared to CTED. End-systolic EI and end-diastolic EI correlated with pulmonary vascular hemodynamic indices and exercise variables, including mean pulmonary arterial pressure , cardiac output  NTproBNP  and 6-min walk distance . Pulmonary artery distensibility also correlated with 6-min walk distance .Eccentricity index at end-systole and end-diastole were higher in CTEPH compared to controls (1.3 ± 0.5 vs. 1.0 ± 0.01; Eccentricity index and pulmonary artery distensibility can detect the presence of pulmonary hypertension in chronic thromboembolic disease and differentiate between CTEPH and CTED subgroups. These measures support the use of non-invasive tests including CMR for the detection pulmonary hypertension and may reduce the requirement for right heart catheterization. Chronic thromboembolic pulmonary hypertension (CTEPH), classed as Group IV in the 2018 National Institute for Health and Care Excellence classification of pulmonary hypertension .The clinical consequences of CTEPH include impaired exercise capacity, right heart failure and premature death . The manTherefore, diagnosis of pulmonary hypertension is key in differentiating between CTEPH and CTED and therefore making a difference to the treatment offered. Echocardiography remains the main screening investigation for pulmonary hypertension. However, there are limitations in obtaining good image windows can often render this technique difficult in many patients, for example those who are obese. Right heart catheterization (RHC) remains the gold standard diagnostic technique for pulmonary hypertension  but thisCardiac MRI is employed with increasing frequency for the assessment of patients with pulmonary arterial hypertension because of increased availability, ease of use and shortened acquisition times . CMR hasWe hypothesized that EI would be abnormal in CTEPH and normal in CTED and that we could use this investigation to differentiate between normal and disease states that would benefit from medical/surgical treatment. Evaluation of pulmonary artery distensibility and peak pulmonary blood flow in these groups were also undertaken. We correlated these findings with right heart catheterization hemodynamic indices, functional capacity using 6-min walk distance, cardiopulmonary exercise testing and cardiac biomarker, N-terminal pro B-type natriuretic peptide (NT-proBNP).This study was approved by the East of England—Cambridge Central Research Ethics committee (20/EE/0195).Patients referred for investigation of potential CTEPH and CTED between January 2016 and December 2019 were identified from a clinical database at the Scottish Pulmonary Vascular Unit (SPVU), Glasgow, UK. Recruitment of patients is summarized in Consecutive patients with complete data sets were included in the analysis . Over thCardiac magnetic resonance imaging was performed using a 1.5-T magnetic resonance imaging scanner  in the headfirst supine position, with gated cardiac synchronization. Initial scout images were acquired using fast imaging with steady state precession. Vertical and horizontal long axis cines were planned and acquired based on the scout images. The short axis images were then planned from the horizontal long axis views. RV and LV volumes were determined by automatic tracing of endocardial borders of the short axis stack using Circle Cardiovascular imaging software . All borders were manually verified and corrected as needed. Main pulmonary artery flow curve was captured using velocity-encoded (VENC) CMR, perpendicular to the pulmonary artery. A VENC of 100 cm/s was used for image acquisition. EI was measured at end systole and end diastole in both left and right ventricles (RV) at mid-ventricular level—defined as the level of the papillary muscles. The EI is defined as the ratio of the length of the two perpendicular minor-axis diameters, one of which is bisected and was perpendicular to the interventricular septum , 3. The D1 is the endocardial measurement perpendicular to the interventricular septum at the largest diameter. D2 is the endocardial measurement at the largest length. D2/D1 is used to calculate eccentricity index in end-diastole and end-systole. These can be difficult to define in pulmonary hypertension, so, using the QRD complex to identify systole, images were identified around the end of systole and the end diastole. These were analyzed and those with the smallest LV volume were classed as end-systole and those with the largest were classed as end-diastole.2 and high VE/VCO2 to assess the level of functional limitation.Cardiopulmonary exercise testing was performed using an incremental cycle ergometer. The ramp rate was chosen by the physiologist, based on participants’ self-reported fitness, with the aim of exercising for 8–12 min. We used the indices of low peak VORight heart catheterization was performed. Hemodynamic parameters including right atrial, right ventricular, pulmonary artery and pulmonary artery wedge pressure were all measured at rest. Cardiac output was measured using the thermodilution method and pulmonary vascular resistance (PVR) calculated. CMR, CPET and right heart catheterization were performed with a maximum of 3 days between procedures.Diagnosis was agreed by consensus at the multidisciplinary team meeting at the Scottish Pulmonary Vascular Unit (SPVU) and by the national pulmonary thromboendarterectomy team at Royal Papworth Hospital, Cambridge, UK.t-test was used to compare normal distributed variables. Mann Whitney U test was used to compare non-normally distributed variables. Spearman correlation was used to assess for correlations between investigations. Analysis of Variance (ANOVA) was used to assess for differences between more than two groups. Receiver Operator Curves were used to identify thresholds of clinical sensitivity and specificity for the investigations. Twenty percentage of images were reviewed by a second observer (>10 years experience), who was blinded to the diagnosis and RHC values, and Pearson’s correlation is used to assess for agreement between continuous variables. A p-value < 0.05 was taken to represent statistical significance. Data were analyzed using Microsoft Excel and GraphPad Prism .Unpaired We identified 30 patients recently diagnosed with CTEPH and 20 control patients with normal resting pulmonary artery values who had a complete data set of investigations. 10 of those with CTEPH were deemed to have distal CTEPH and 20 with proximal disease. There were no significant differences in age and sex between these groups.p ≤ 0.01), PVR  were higher in patients with CTEPH vs. controls. Pulmonary artery wedge pressure was normal in both groups. NTpro-BNP was significantly higher in patients with CTEPH vs. non-PH .Baseline characteristics are shown in 2 between groups but VE/VCO2  was higher in CTEPH, in keeping with increased dead-space ventilation.Cardiopulmonary exercise testing parameters are outlined in p ≤ 0.01) with a significantly higher EI in systole  and diastole  compared to the control group. We showed that PA diastolic area was significantly higher in the pulmonary hypertension group . There was no significant difference in peak pulmonary artery blood flow velocity.Differences in the novel geometric CMR indices in those with pulmonary hypertension and those without are shown in R-value 0.74, p ≤ 0.01) and with diastolic LVEI . Systolic and diastolic EI also correlated with prognostically important markers including PVR , mixed venous saturations  and 6-min walk distance  (Mean pulmonary artery pressure correlated with systolic LVEI (ctively) .2 in the CTEPH group, this did not reach statistical significance. However, there was a progressive rise in the VE/VCO2 (p ≤ 0.01), consistent with greater dead-space ventilation in those with CTEPH.Those with distal CTEPH in our group were unable to perform cardiopulmonary exercise testing due to physical limitations, and, as such there is no data available for this group. CPET data for the other three groups are outlined in R = 0.9).We have shown good interobserver agreement in our CMR determinants, lending confidence to our results using Pearson’s correlation , diastolic index is 1.1 (AUC = 0.94) and pulmonary artery distensibility is 0.28 (AUC = 0.95). We found no meaningful threshold for the peak blood flow .p ≤ 0.01), a progressive reduction in the cardiac index (p ≤ 0.01) and rise in the PVR (p ≤ 0.01).Patients without pulmonary hypertension were divided into two groups—those without evidence of pulmonary vascular obstruction on CT and V/Q imaging , and those with residual radiological proven disease. Differences in the hemodynamic indices across those who had normal pulmonary vasculature, those with CTED and those with proximal and distal CTEPH were compared . As expep ≤ 0.01), diastolic LVEI (p ≤ 0.01), and pulmonary artery distensibility (p ≤ 0.01). No significant differences between subgroups in peak blood flow were seen.The differences between groups in the geometric novel CMR indices are shown in p ≤ 0.01] and PVR  were higher in the CTED group, in keeping with pulmonary vascular occlusions. In addition, there was a significantly lower pulmonary artery distensibility  and a significantly higher LVEI in systole  and diastole  in the CTED group compared to normal but no significant difference in peak blood flow between these groups. Threshold analysis for identifying the presence of CTED using systolic and diastolic LVEI is 1.0 and pulmonary artery distensibility is 0.37 , and those with residual radiological proven disease were evaluated . Age and is 0.37 .In this retrospective cohort study of patients, we have demonstrated three important findings.•That elevated EI, both in systole and diastole, and reduced pulmonary artery distensibility are predictive of the presence of pulmonary hypertension in CTEPH.•Both EI and pulmonary artery distensibility could discriminate between the normal, CTED and CTEPH population.•Both systolic and diastolic EI correlate with clinical markers of outcome.Furthermore, using a CMR EI threshold of 1.1 has a high sensitivity and specificity for the identification of the presence of pulmonary hypertension. To our knowledge, this is the first time the utility of this measurement has been demonstrated in thrombotic pulmonary vascular disease with CMR. In addition, we have demonstrated that lower pulmonary artery distensibility is predictive of the presence of pulmonary hypertension in patients with radiological features of thromboembolic disease. However pulmonary arterial peak blood flow was not useful for the detection of PH. We acknowledge that there has been a change to the hemodynamic values in the definition of pulmonary hypertension in the 6th World Symposium definition. We have chosen to use the 5th World symposium definition because existing evidence for therapy Is based on these criteria, lending more clinical relevance to our findings in detecting patients who may be amenable to treatment options.Cardiac magnetic resonance is the gold standard investigation for assessment of right ventricular function and has the added benefit over echocardiogram of allowing detection of pulmonary vascular occlusion with magnetic resonance pulmonary angiogram. Of additional clinical significance and importance is trying to differentiate patients who have CTED or CTEPH using non-invasive modalities. This is important because management can be different and currently many patients with CTED require right heart catheterization in order to differentiate. The data shown in this paper suggests that patients with vascular obstructions on CT can be differentiated on the basis of presence of PH by using certain CMR thresholds of EI (1.1) and pulmonary artery distensibility (0.28). This is important as currently patients with CTED do not have any therapeutic options and therefore do not routinely need to undergo any invasive investigations. If the patient can manage, using CPET is a useful adjunct in the non-invasive assessment of these patients.vO2 . This contrasts with other studies where imaging has been performed at a different time point from the right heart catheterization , 20. We However, this paper confirms that CMR parameters can be used in conjunction with other invasive and non-invasive investigations to evaluate patients who are suspected as having pulmonary vascular disease and allow clinicians to establish the diagnosis and determine appropriate management. This is an important addition to the literature on the management of these conditions.In this retrospective cohort study of patients, we have demonstrated three important findings. Firstly, that elevated EI, both in systole and diastole, and reduced pulmonary artery distensibility are predictive of the presence of pulmonary hypertension in CTEPH. Secondly, both EI and pulmonary artery distensibility could discriminate between the normal, CTED and CTEPH population, and finally, both systolic and diastolic EI correlate with clinical markers of outcome. These have not been demonstrated before in chronic thromboembolic pulmonary vascular disease using CMR.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.This study was approved by the East of England—Cambridge Central Research Ethics committee (20/EE/0195). Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.MM was the main author of the manuscript. HD contributed to the gathering of non-invasive measurements. MB and MJ contributed to the gathering of invasive and non-invasive measurements. NL reviewed the manuscript before submission. AC contributed to the gathering of invasive and non-invasive measurements and review of the manuscript. All authors have read and approved the manuscript.


Multivalvular heart disease (MVD) is an aggregate of regurgitant and/or stenotic lesions of at least two cardiac valves. Ventricular tissue deformation imaging is a powerful predictor of subclinical myocardial dysfunction in patients with MVD.The aim of this study was to examine the left and right ventricular strain patterns in MVD as well as observe any association between right–sided valvular involvement  with that of aortic and/or mitral valve lesion. Patients with at least moderate forms of MVD were included in the present study. 72 patients with mean age of 56.69 ± 14.59 years and various presentations of MVD were finally enrolled in this study. The commonest cause for MVD was rheumatic heart disease in these patients. Conventional 2-dimensional parameters as well as tissue deformation imaging parameters were assessed in offline mode for these patients. The Mean ± SD values for various quantitative 2D echocardiographic conventional and tissue deformation imaging were assessed. It was observed that LV strain parameters including the global longitudinal strain (GLS) were preserved whereas the RV strain parameters were mildly reduced . Also, when conventional echocardiographic parameters were assessed to see any association between aortic and/or mitral valve disease with that of right-sided valvular lesions (tricuspid or pulmonary); 2D conventional echocardiographic parameters like left atrial dimension (p = 0.034), TAPSE (tricuspid annular plane systolic excursion) (p < 0.001), RVSP (right ventricular systolic pressure) (p < 0.001) and IVC (inferior vena cava) dimensions (p < 0.001) showed a statistically significant result; whereas, when strain parameters for LV and RV were assessed, they did not show any statistical difference for the same. In this series of patients with significant MVD, our findings suggest that ventricular strain parameters may be reliable markers of myocardial dysfunction, but may alter depending on the underlying combination of MVD, and right ventricular strain should also be an important parameter while assessing different combinations of MVD. Multivalvular heart disease (MVD) is defined as aggregate of regurgitant and/or stenotic lesions of at least two cardiac valves . Valves Global prevalence for MVD was reported to be 63.9 per 1, 00,000 person-years . AccordiStrain echocardiography/tissue deformation imaging, is one of the best imaging echocardiographic modality in diagnosis and prognostic evaluation of valvular lesions. Indication for use of strain imaging in MVD is to detect subclinical myocardial dysfunction before an overt reduction of LV ejection fraction and thus can be used to determine the exact intervention time before the ventricular function further deteriorates and also determines prognosis of MVD .Most of the patients visiting our cardiology OPD present with either single (more common) or with concomitant multiple valvular lesions. Limited studies focused on ventricular loading response to multivalvular heart disease in literature. Tissue deformation imaging in identifying subclinical myocardial dysfunction among these population have not been studied thoroughly.This study is one of its kind to emphasize ventricular strain mechanics in multiple valvular disease loading conditions. The purpose of this study was to assess left and right ventricular strain patterns in multivalvular heart disease and also to assess involvement of right sided valvular lesions with aortic and/or mitral valvular lesions.A total of 72 patients with MVD involving more than or equal to two valves with a severity of at least more than moderate valvular lesion examined in echocardiography laboratory at the Department of Cardiology, KMC, Manipal enrolled from March 2020 to May 2021 were considered eligible for the study. Exclusion criteria included any associated ischemic heart disease, LV ejection fraction < 50%, previous history or intracardiac/prosthetic heart surgery and restrictive cardiomyopathy(RCM).The study protocol was intended to have sample size of 100 as we wished to take samples based on time bound pattern;i.e., 5 to 10 patients per month. The study was approved by the Board of Ethics Committee, Kasturba Hospital, Manipal (contact no.0820–292371) and also the subjects gave the informed consent.Clinical data included age, gender, height, weight, body mass index, history of hypertension and diabetes, smoking or drinking status, food habits and history of coronary artery disease of the subjects. Also, surface electrocardiographic (ECG) recordings of the subjects were taken and reported.At entry in the study, all patients underwent a comprehensive echocardiography using commercially available equipment  at rest. Standard views were obtained with patient positioned in left lateral decubitus position. Standard views  views were recorded and stored LVEF measurements are taken by M mode and Simpson’s method. Left ventricular (LV) end diastolic dimensions  were acquired from the parasternal long axis view at the mitral valve leaflet tips. TAPSE values obtained from M mode at tricuspid valve annulus. 2 dimensional tissue deformation imaging of LV and RV strain parameters were measured offline in an echocardiography core laboratory using dedicated commercial software system (Echo-Pac) Fig. . Three cAll data were entered in excel sheet. Statistical analysis was carried out using the EZR (32 bit) version 1.37. Continuous variables was expressed as Mean ± SD and compared using one way analysis of variance. Categorical data was expressed as frequency, percentage and analyzed using Chi Square test. Results were considered significant with p value less than 0.05.All patients who met the inclusion criteria and met no exclusion criteria were included for analysis on the basis of their diagnosis. This study included 72 patients with MVD with mean age of 56.69 ± 14.59 years, among them 34(42.7%) were males and 38(52.8%) were females, and other baseline demographic and clinical characteristics are mentioned in  along with concomitant right- sided valvular lesions (tricuspid/pulmonary); remaining patients had AR and MR, AR and MS, AS and MR, AS and MS respectively , none of them showed a statistically significant result.In the present study, 72 individuals  were enrolled after confirming that they had at least moderate forms of multivalvular disease involving any 2 or more cardiac valves. Out of these 72 subjects, 11 of them had already undergone percutaneous balloon mitral valvulotomy (BMV) for mitral stenosis but still had persisting mild to moderate degrees of mitral stenosis.The demographic and clinical features of the patients are given in Table Rheumatic heart disease (RHD) defined as a manifestation of rheumatic fever, an autoimmune disorders affecting multiple organ systems, is a disease associated with poor hygiene, overcrowding, poverty and low socioeconomic status –9. In InIn 1943, Don Carlos et al.  reportedHowever, in the present study, majority of individuals with MVD were non vegetarians, 4968.1%) rather than vegetarians, 23(31.9%)  and least were degenerative valvular disease13.5%)  , other LV echocardiographic parameters and even strain parameters (LV-GLS: 17.49 ± 41.17%) were normal Table . This maIn the present study, out of 72 patients with MVD, 38 of them had right—sided valvular disease  with mitral and/or aortic valve disease. When RV echocardiographic parameters were compared 2D derived left atrial dimensions (p = 0.034) was significant; TAPSE (p < 0.001), RVSP (p < 0.001) and IVC dimensions (p < 0.001) showed highly statistically significant result  and due to some inflammatory changes due to rheumatic disease in RHD cases –20.Unequal gender distribution and multivalvular disease type is the major limitation in our study due to constricted time limit. Smaller sample size due to ongoing COVID pandemic, this may have limited our ability to detect significant associations with other factors in MVD subjects.Despite of having any presentation of MVD, the prognosis and course of treatment should be based on approach to individual valvular lesions, as the use of strain echocardiographic parameters alone is not sufficient.We have provided new insights about alterations in ventricular strain patterns for different combinations of MVD. Subclinical myocardial dysfunction assessment using strain echocardiography is again dependent on various loading conditions on the ventricles and severity of the lesions. Also, it is extremely important that RV strain analysis should even be employed for MVDs affecting the left-sided heart valves alone.


Despite poor cardiovascular outcomes, there are no dedicated, validated risk stratification tools to guide investigation or treatment in type 2 myocardial infarction.The goal of this study was to derive and validate a risk stratification tool for the prediction of death or future myocardial infarction in patients with type 2 myocardial infarction.T2-risk score was developed in a prospective multicenter cohort of consecutive patients with type 2 myocardial infarction. Cox proportional hazards models were constructed for the primary outcome of myocardial infarction or death at 1 year using variables selected a priori based on clinical importance. Discrimination was assessed by area under the receiving-operating characteristic curve (AUC). Calibration was investigated graphically. The tool was validated in a single-center cohort of consecutive patients and in a multicenter cohort study from sites across Europe.The T2-risk score incorporating age, ischemic heart disease, heart failure, diabetes mellitus, myocardial ischemia on electrocardiogram, heart rate, anemia, estimated glomerular filtration rate, and maximal cardiac troponin concentration had good discrimination  for the primary outcome and was well calibrated. Discrimination was similar in the consecutive patient  and multicenter  cohorts. T2-risk provided improved discrimination over the Global Registry of Acute Coronary Events 2.0 risk score in all cohorts.There were 1,121, 250, and 253 patients in the derivation, single-center, and multicenter validation cohorts, with the primary outcome occurring in 27% , 26% (66 of 250), and 14% (35 of 253) of patients, respectively. The T2-risk score performed well in different health care settings and could help clinicians to prognosticate, as well as target investigation and preventative therapies more effectively. The   The GRACE  2.0 scoreWe aimed to derive and validate a new risk stratification tool for use in patients with type 2 myocardial infarction to determine the likelihood of future myocardial infarction or death that could assist clinicians in the targeting of further investigation and secondary prevention.NCT01852123). All patients presenting between June 10, 2013, and March 3, 2016, were screened by the attending clinician and prospectively included if cardiac troponin assessment was requested for suspected acute coronary syndrome. Individual patient consent was not sought. The study design has been described in detail previously,,High-STEACS  was a stepped-wedge, cluster randomized controlled trial that evaluated the implementation of a high-sensitivity cardiac troponin I (hs-cTnI) assay in consecutive patients with suspected acute coronary syndrome across 10 secondary and tertiary care hospitals in Scotland . Adults presenting to the emergency department with chest pain at rest or on minor exertion within 12 hours from presentation were enrolled following receipt of written informed consent. Patients with end-stage kidney failure requiring regular dialysis or with cardiogenic shock were excluded. The study was conducted according to the principles of the Declaration of Helsinki and approved by the local ethics committees.APACE  is a prospective, multicenter, international study that enrolled patients from April 25, 2006, until February 2, 2018, with chest pain from 12 centers across 5 countries in Europe . This assay has a limit of detection of 1.2 ng/L, an interassay coefficient of variation of <10% at 4.7 ng/L, and a 99th centile of 16 ng/L in women and 34 ng/L in men.,In all cohorts, all diagnoses were adjudicated in patients with evidence of myocardial injury in accordance with the fourth universal definition of myocardial infarction.,,In all cohorts, 2 physicians independently reviewed all clinical information, with discordant diagnoses resolved by a third reviewer or by consensus as previously described.The primary outcome was subsequent myocardial infarction or death from any cause at 1 year. The secondary outcome was subsequent myocardial infarction or cardiovascular death at 1 year. In the derivation cohort, regional and national registries were used to ensure complete follow-up for the trial population as previously described.All index admission myocardial infarction events were excluded in all 3 cohorts.Baseline characteristics were summarized for patients with type 2 myocardial infarction enrolled in the derivation and validation cohorts. Continuous variables are described by using mean ± SD or median (IQR) as appropriate; categorical variables are described as frequencies and percentages. Where data were missing in the derivation cohort, this was assumed to be at random after visual inspection, and multiple imputation using chained equations was performed .T2-risk score was based on the model constructed for the primary outcome. For both models, covariates were defined a priori based on clinical knowledge and the availability of data, including variables that are objective and readily available to clinicians.,Survival analysis was performed by using Cox proportional hazards models for the primary and secondary outcomes separately. For the secondary outcome, noncardiovascular deaths were censored to account for competing risks in a cause-specific model. The derivation of the T2-risk score vs the GRACE 2.0 algorithm using the DeLong test.Continuous variables, including age, estimated glomerular filtration rate, and heart rate, were modeled by using restricted cubic splines to account for nonlinearity using 4, 3, and 3 knots, respectively. Cardiac troponin concentration was log transformed. Categorical variables included anemia  using R version 3.6.3 . All findings are reported in accordance with the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis statement  had evidence of myocardial injury, with type 2 myocardial infarction in 10%   had myocardial injury. Sufficient clinical information was available to adjudicate the diagnosis in 88%  of patients. The final diagnosis was type 2 myocardial infarction in 12% , with 2 outliers excluded, giving a total of 1,119 patients for the derivation cohort. The single-center consecutive patient cohort was derived from 22,589 consecutive patients with suspected acute coronary syndrome, of whom 17%  had myocardial injury. The final diagnosis was type 2 myocardial infarction in 7%  of patientsf 2,529) .Figure 1Patients with type 2 myocardial infarction were of similar age in all cohorts . A similar proportion of men and women were recruited in the consecutive patient cohorts ; however, a higher proportion of men were enrolled in the multicenter, international validation cohort (65%). Patients in the derivation and multicenter, international validation cohorts had a higher incidence of cardiovascular disorders such as ischemic heart disease, previous myocardial infarction, and cerebrovascular disease than the single-center validation cohort. Physiological parameters were broadly comparable .Table 1BThe primary outcome of myocardial infarction or all-cause death at 1 year occurred in 27%  of the derivation cohort  and in 2T2-risk score displayed good discrimination   and both validation cohorts  . For the73-0.79) . Further73-0.79) . We comp cohorts .Table 3UIn the single-center, consecutive patient validation cohort, discrimination was similar for both the primary  and secondary  outcomes. In the multicenter, international validation cohort, discrimination was similar for the primary outcome  and secondary outcome   and 2C. T2-risk score was applied to define patients at high risk (predicted event rate >34%) and the lower quartile applied to define patients at low risk (predicted event rate <13%). In the derivation cohort, the observed rate of subsequent myocardial infarction or death was 51% (147 of 286) at 1 year in those identified as high risk and 7% (19 of 267) in those at low risk , systemic , and tachyarrhythmia  phenotype. A systematic assessment of available covariates for the prediction of the primary outcome is shown in When primary outcome events up to 30 days were excluded to account for critical illness, the model performance was similar in both the derivation  and validation  cohorts, respectively. To ensure imputation did not influence results, a complete case analysis was undertaken, showing no difference in model performance . The modT2-risk model showed improved performance for the prediction of myocardial infarction or death from any cause. Importantly, the T2-risk score performed well in 2 independent external validation cohorts and displayed consistent performance in men and women. In the future, this tool may be helpful for clinicians in practice to identify patients at highest risk of future cardiovascular events.We have derived and externally validated a risk stratification tool to guide prognostication in patients with type 2 myocardial infarction. We show that routinely recorded clinical variables can be used to estimate the likelihood of subsequent myocardial infarction and death from any cause or death from cardiovascular disease at 1 year . ComparePrior research has shown that the guideline-recommended GRACE 2.0 algorithm performs less well in patients with type 2 myocardial infarction than in those with type 1 myocardial infarction.T2-risk score facilitates identification of patients at highest risk of future myocardial infarction or death. Although we trained the T2-risk score for this outcome to enable a direct comparison with the GRACE 2.0 score, heart failure is also an important outcome for patients with type 2 myocardial infarction, and it is likely that risk prediction could be further refined with cardiac imaging. In patients with type 2 myocardial infarction, coronary disease and left ventricular dysfunction are highly prevalent. In a prospective cohort study enrolling patients with type 2 myocardial infarction, coronary artery disease was identified in 68% of patients and was obstructive in 30%.T2-risk score could be used to target further investigation such as echocardiography, computed tomography imaging, or invasive coronary angiography to guide secondary prevention therapy requires prospective evaluation.The T2-risk score could be in the identification of those at low risk of future adverse outcomes who may not require further investigation. In the consecutive patient validation cohort, our risk thresholds identified similar proportions of patients at high and low risk of future events. We acknowledge that the proportion of high- and low-risk patients differed in the multicenter, international cohort. This likely reflects the recruitment of a lower risk population, as individual patient consent was sought to obtain additional research samples for storage. However, despite variation in the prevalence of type 2 myocardial infarction and risk profile of those enrolled across our validation cohorts, the T2-risk model performed consistently well.Although patients with type 2 myocardial infarction are at a higher overall risk of adverse outcomes, there are phenotypes of patients who are at lower risk such as those presenting with type 2 events secondary to tachyarrhythmia.T2-risk score was developed from a large consecutive patient cohort, including all who presented to the hospital with suspected acute coronary syndrome, avoiding selection bias and including the largest number of consecutive patients with an adjudicated diagnosis of type 2 myocardial infarction. The score was validated in 2 independent patient cohorts encompassing 11 sites in 5 countries across Europe in both consecutive and selected patients. In all cohorts, the diagnosis of myocardial infarction was adjudicated in line with the fourth universal definition using high-sensitivity cardiac troponin assays.Our analysis has several strengths. The T2-risk score was derived in patients who were resident in Scotland and treated in a single health care system. However, we provide external validation in 2 independent cohorts showing that our findings are generalizable. To mitigate for competing risks in the prediction of future cardiovascular events in the secondary model, we censored for noncardiovascular death. Although this approach has been validated, this may lead to overprediction of secondary outcomes.T2-risk model in patients with acute nonischemic myocardial injury, but these patients share similar characteristics and outcomes, and it would be of interest to evaluate in future studies. The derivation and validation cohorts used the hs-cTnI and hs-cTnT assay, respectively, but we modeled the relationship in patients with both concentrations measured and applied a linear regression correction, revealing robust performance. We used multiple imputation for missing variables in the derivation cohort that were presumed to be at random, and showed in a sensitivity analysis that similar performance was observed in the complete data set without imputation. We were not able to incorporate all physiological parameters nor include phenotypic information known to influence prognosis. Although all index and outcome events were adjudicated in the derivation cohort and the multicenter validation cohort, ICD-10 coding was used for outcomes in the single-center validation cohort, which could contribute to misclassification and underestimate T2-risk model performance. Finally, although our risk stratification tool seems to delineate risk well, prospective evaluation is required if it is to be used to guide treatment decisions in practice.Although the GRACE 2.0 algorithm was derived in a global registry, the T2-risk score performs well in different health care settings and could help clinicians prognosticate, as well as target investigation and preventative therapies more effectively.PerspectivesCOMPETENCY IN PATIENT CARE AND PROCEDURAL SKILLS: A stratification tool derived and externally validated in patients with type 2 myocardial infarction improves prediction of re-infarction or death at 1 year.TRANSLATIONAL OUTLOOK: Whether management guided by this risk stratification tool can improve outcomes in patients with type 2 myocardial infarction at highest risk of recurrent ischemic events requires prospective investigation.A novel risk stratification tool predicts myocardial infarction and death from any cause or cardiovascular disease at 1 year with good discrimination in patients with type 2 myocardial infarction. The This project was funded by a Starter Grant for Clinical Lecturers from the Academy of Medical Sciences . This work was also supported by DataLoch, which is funded by the Data Driven Innovation programme within the Edinburgh and Southeast Scotland City Region Deal. The High-STEACS trial was funded by a Special Project Grant (SP/12/10/29922) from the British Heart Foundation with assay reagent, calibrators, and controls provided by Abbott Laboratories without charge. Dr Taggart is supported by a British Heart Foundation Clinical Research Training Fellowship (FS/CRTF/21/2473). Dr Monterrubio-Gómez is supported by an MRC University Unit grant to the MRC Human Genetics Unit. Dr Vallejos is a Chancellor’s Fellow supported by the University of Edinburgh. Drs Wereski and Bularga are supported by Clinical Research Training Fellowships from the Medical Research Council (MR/V007017/1 and MR/V007254/1). Dr Mills is supported by a Chair Award, Programme Grant, Research Excellence Award , from the British Heart Foundation, Drs Vallejos and Mills are supported by a British Heart Foundation–Turing Cardiovascular Data Science Award (BCDSA/100003). Dr Mills has received honoraria or consultancy from Abbott Diagnostics, Roche Diagnostics, Siemens Healthineers, and LumiraDx. Dr Roos was supported by the Stockholm County Council (grant no. 20200935). Dr Boeddinghaus has received research grants from the University of Basel, the University Hospital of Basel and the Division of Internal Medicine, the Swiss Academy of Medical Sciences, the Gottfried and Julia Bangerter-Rhyner-Foundation, and the Swiss National Science Foundation; and has received speaker honoraria and/or consulting honoraria from Siemens, Roche, Ortho Clinical Diagnostics, and Quidel Corporation, outside of the submitted work.). Dr Nestelberger has received research support from the Swiss National Science Foundation (P400PM_191037/1), the Swiss Heart Foundation (FF20079), the Prof Dr Max Cloëtta Foundation, the Margarete und Walter Lichtenstein-Stiftung (3MS1038), the University of Basel, and the University Hospital Basel; and has received speaker honoraria/consulting honoraria from Siemens, Beckman Coulter, Bayer, Ortho Clinical Diagnostics, and Orion Pharma, all outside the submitted work. Dr Koechlin received a research grant from the Swiss Heart Foundation, the University of Basel, the Swiss Academy of Medical Sciences, and the Gottfried and Julia Bangerter-Rhyner Foundation, and the Freiwillige Akademische Gesellschaft Basel. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.


In many cardiac diseases, right and left ventricular volumes in systole and diastole are diagnostically and prognostically relevant. Measurements are made by segmentation of the myocardial borders on cardiac magnetic resonance (CMR) images. Automatic detection of myocardial contours is possible by signal thresholding techniques, but must be validated before use in clinical settings. Biventricular volumes were measured in end-diastole (EDVi) and in end-systole (ESVi) both manually and with the MassK application, with signal thresholds at 30%, 50%, and 70%. Stroke volumes (SV) and cardiac indices (CI) were calculated from volumetric measurements and from flow measured in the ascending aorta and the main pulmonary artery, and both methods were compared. Reproducibility of volumetric measurements was tested in 20 patients. Measurements were acquired in 94 patients aged 15 ± 9 years referred for various conditions. EDVi and ESVi of both ventricles were largest with manual segmentation and inversely proportional to the MassK threshold. Manual and k30 SV and CI corresponded best to flow measurements. Interobserver variability was low for all volumes manually and with MassK. In conclusion, manual and 30% threshold-based biventricular volume segmentation agree best with two-dimensional, phantom-corrected phase contrast flow measurements in a young cardiac referral population and are well reproducible. Diagnosis and prognosis in many cardiovascular diseases rely on the accurate quantification of left and right ventricular volumes as well as myocardial mass measurements ,3,4,5,6.Newer MR post-processing algorithms use automatic myocardial contour detection based on signal thresholding. This technique improves discrimination between myocardium and blood, is less operator-dependent and reduces post-processing time ,18. HoweOur aim was to assess the accuracy of semi-automated CMR imaging segmentation measurements of ventricular volumes and mass, as well as of calculation of stroke volume (SV), and cardiac index (CI) for the LV and the right ventricle (RV). We aimed to validate these parameters against both ventricular manual contour drawing measurements and phantom corrected 2D flow measurements and to test reproducibility.We retrospectively reviewed consecutive data acquired in our institution between January 2018 and March 2019. Inclusion criteria consisted of biventricular cardiac physiology, MR studies containing steady-state free precession (SSFP) images for ventricular function and two-dimensional phase contrast (2D PC) flow sequences. Exclusion criteria were defined as: incomplete MR data; lack of consent for retrospective data analysis; significant stenosis or regurgitation in one or more cardiac valves shown by 2D PC flow or by echocardiography; implantable cardiac device; major arrhythmia during the scan.The ethics committee of the canton of Zurich, Switzerland (KEK-Nr. 2019-00422) approved the conduct of this study, and all patients, their parents or legal guardians, gave informed consent to the use of their data.All CMR studies were performed with a 1.5 Tesla scanner . Subjects were imaged in supine position during breath-hold at end-expiration. SSFP images were acquired in a stack of short axis slices covering both ventricles with the following parameters: 40 cardiac phases, 10–13 slices as appropriate, slice thickness 6–8 mm depending on body size, interslice gap 0–2 mm, temporal resolution <30 ms, echo time 1.5–1.8 ms, repetition time 3.5–4.2 ms, flip angle 45°, matrix size 224 × 224, field of view 280–420 mm. Vertical and horizontal long axis planes were used for correct perpendicular planning of the short axis images.Phantom-corrected 2D PC images were acquired for flow measurements perpendicular to the ascending aorta at the level of the right pulmonary artery and in the main pulmonary artery (MPA) midway between the pulmonary valve and the bifurcation, this was used as an independent reference standard . AcquisiImage quality was assessed visually. All ventricular volumes were measured twice; once using the contour-based method and once using the threshold-based method. To avoid bias, both measurements were performed by the same operator in a time interval of more than two weeks.Manual contour-based segmentation was performed on SSFP short axis images using QMass  as previously reported ,20. TPM Threshold-based volumes were calculated on the same SSFP images with the MassK thresholding algorithm of the same software. The same end-systolic and end-diastolic phases and the same epicardial contours defined manually were utilized for MassK application. The MassK algorithm discriminates blood from myocardium by analysis of voxel signal intensity as described by Jasper et al. . Measure2]) were used as references for ventricular SV and CI calculated by both methods.Velocities and flow volumes were calculated using QFlow software . All 20 phases were contoured by using a semi-automated algorithm followed by manual correction where necessary. Offset errors were corrected using phantom acquisitions . The SV Interobserver variability was tested by comparing manual contours and threshold-based contours performed by two independent observers of different experience grade (TT and BB) in 20 patients.2]) and mass indices (mass/BSA [g/m2]) using manual segmentation (QMass) and semi-automated segmentation (MassK) were compared using paired t-tests and Pearson’s correlation coefficients for data with normal distribution, or Wilcoxon tests and Spearman’s correlation coefficients for non-normally distributed data, respectively. Patient groups were compared using the Mann–Whitney test. Bland–Altman analysis was used to assess agreement between the different segmentation techniques and interobserver variability [Statistical analysis was performed using GraphPad Prism version 8.4.3 for OS X . D’Agostino-Pearson omnibus normality test was used to check distribution of data. Mean±standard deviation was used to present normally distributed values and median ± interquartile range for non-normally distributed values. LV and RV volume indices (volume/body surface area (BSA) [mL/miability . InterobP values < 0.05 were considered statistically significant.Coefficient of variation was calculated as standard deviation of a measurement divided by the mean value. n = 17), Kawasaki disease (n = 6), hypertrophic cardiomyopathy (n = 3), Marfan disease (n = 2), metabolic disease (n = 1), and noncompaction cardiomyopathy (n = 1). Congenital heart disease included corrected dextro-transposition of the great arteries (n = 13), total anomalous pulmonary venous return (n = 4), partial anomalous pulmonary venous return (n = 3), ventricular septal defect (n = 2), anomalous left coronary artery origin from the pulmonary artery (n = 1), hypoplastic pulmonary arteries (n = 1), double outlet RV (n = 1) and atrioventricular septal defect (n = 1). Aortic pathology included coarctation of the aorta (n = 9), bicuspid aortic valve (n = 6), interrupted aortic arch (n = 3), vascular ring (n = 2), aortic dissection (n = 1), aortic aneurysm (n = 1), and double aortic arch (n = 1). Healthy subjects underwent CMR for screening purposes but showed normal cardiac anatomy and function. Others were LV fibroma (n = 1) and LV carcinoma (n = 1).A total of 94 patients  fulfilled the inclusion criteria. Details about demographics, patient characteristics, and diagnoses are described in Ventricular volumes calculated by manual segmentation and by threshold-based contouring with 3 different threshold values  as well as flow volumes measured in the aorta and MPA are reported in p < 0.0001 for all). Additionally, RV EDVi and RV ESVi were significantly smaller than by manual measurements .As expected, the largest volumes (EDV and ESV) were measured with manual segmentation in both ventricles. Volumes decreased steadily with increasing thresholds. At all threshold settings used, LV EDVi and LV ESVi were significantly smaller than by manual measurements, respectively (p < 0.0001 for both).Similarly, myocardial mass showed the lowest values with manual segmentation and increased with increasing thresholds. At a threshold of 50%, LVMi and RVMi were significantly greater than manual measurements , and between patients with  RVEF below median versus above median .There was a greater discrepancy between manual and flow-derived stroke volumes in patients with  LVEF above median versus below median  or with  RVEDVi below versus above median (p = 0.368).The discrepancy between manual stroke volumes and flow-derived stroke volumes of the respective ventricle was not statistically different between patients with  LVEDVi below median versus above median (p = 0.012) but was greater with lower versus higher  RVEF  and lower versus higher  RVEDVi , with no statistical significance between LVEDVi strata (p = 0.057)  LVEF  .2). All CI measurements (LV and RV) with manual, all threshold-based methods, and flow showed small biases between the two readers . In readings for RV volumes, the threshold-based method showed overall smaller biases when compared to the manual method  by threshold-based  and manual measurements showed acceptably small biases between the two readers  with a broad variety of different diagnoses reflective of part of a typical clinical referral population. In addition, we evaluated not only LV, but also RV volume and mass measurements, which are important in many congenital heart diseases .Our study showed better interobserver agreement for RV volumes with the threshold-based compared to the manual method. Excellent interobserver agreement was found for biventricular EDVi and CI. Of all parameters, RV ESVi and the mass indices of both ventricles showed the highest interobserver variability by all methods, which exemplifies the importance of manual epicardial tracing, including in the RV outflow tract. This is a potential source of error that cannot be overcome by the semi-automated thresholding technique. At the same time, RV CI showed the least bias from flow measurements by manual volumetrics.To our knowledge, we provide the first evaluation of biventricular threshold-based volumetrics in a varied, clinical referral population of young patients with different congenital and acquired heart diseases using phantom-based flow as a reference standard. Patients with valvular dysfunction were excluded in order to avoid flow alterations and to use only valid flow data . We demoLimitations of this study are its retrospective nature and a small patient population, although greater than in previous published studies. Our results may not be generalizable to healthy individuals, as has been done before by others , becauseIn conclusion, our results show sufficient accuracy of the MassK threshold-based algorithm for the evaluation of LV and RV volumes if the signal intensity threshold is adjusted to 30%. We demonstrate that the threshold-based algorithm is also suitable for young patients with various cardiac pathologies. Excellent agreement was found between observers with different experience levels. Thus, the threshold-based method can be used interchangeably with the conventional manual method to increase efficiency in clinical care, if the user adapts the threshold setting correctly.


What came first the chicken or the egg? The RNA World hypothesis places RNA at the forefront, predating both DNA and protein . That hyLei et al. examine the role played by miR-132/212, using several mouse models of heart failure and cardiac tissue from end-stage heart failure patients. They also developed miR-132/212 KO mice. Their findings indicate that the upregulation of miR-132/212 in the failing heart impairs cardiac contractile function, thereby accelerating heart failure progression. Specifically, they found that miR-132/212 decreases cardiac contractility by inhibiting expression of SERCA2, as well as by lowering its activity indirectly.Compromised cardiac function due to dysfunction in calcium handling is a hallmark of heart failure that is incompletely understood. Zheng et al. explored the role of circular RNA (circRNA) in iron-related cell death or ferroptosis in heart failure. They re-constructed the circRNA-miRNA-mRNA regulatory network after firstly identifying the iron metabolism-associated genes and confirmed their findings in a mouse model of heart failure due to transverse aortic construction (TAC). Their analysis indicated that increasing levels of miR-224-5p were associated with reduced expression levels of circSnx12 and Fth1 in heart failure with the latter being a coding gene encoding the iron binding protein ferritin heavy chain. It is thus hypothesized that circSnx12 would normally serve to sponge miR-224-5p, which in turn reduces Fth1 expression. Ferritin heavy chain maintains iron in a safe, soluble form. Levels of increased iron, which can cause oxidative stress, and evidence of lipid peroxidation were significantly higher in the TAC group.Wang et al. sought to identify potential long non-coding RNAs (lncRNAs) and mRNAs in the progression from acute myocardial infarction (AMI) to myocardial fibrosis to heart failure. They identified several lncRNA-co-expressed/nearby targeted mRNA pairs that may play key roles in the development of AMI, myocardial fibrosis, and heart failure.Morbidity and mortality from myocardial infarction (MI) remain unacceptably high due to a progression to heart failure. Shen et al. performed a systematic review and meta-analysis to assess miRNA expression profiles in heart failure patients. Their study confirmed a total of 57 consistently dysregulated miRNAs related to heart failure. Moreover, their findings indicate that seven dysregulated miRNAs might be considered potential non-invasive biomarkers for HF. Additional studies are warranted to understand their specific mechanisms of action in heart failure, as well as to explore whether the combinatorial use of these miRNA markers with established HF markers, such as cardiac troponin levels, can improve diagnosis and prognosis of HF compared to existing established methods. Also, it is noteworthy that despite the ease of detection of miRNAs in biosamples with the advances of qPCR methods, there still needs to be done substantial progress to allow the measurement to be performed in an acceptable timeframe and with high enough sensitivity to allow for their application in clinical practice.Circulating miRNAs have gained interest as potential novel heart failure biomarkers because of sequence conservation, high stability, and ease of detection. Xue et al. extensively review the role of exosomal miRNAs in heart failure. They make the case that exosomal miRNAs may be promising diagnostic and therapeutic molecules for heart failure. The processes that they may regulate include cardiac hypertrophy, fibrosis, and angiogenesis. As previously discussed, they may serve as biomarkers in heart failure to evaluate disease progression .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Congestion is a key driver of morbidity and mortality in heart failure. Implanted haemodynamic monitoring devices might allow early identification and management of congestion. Here, we provide a state-of-the-art review of implanted haemodynamic monitoring devices for patients with heart failure, including a meta-analysis of randomised trials.p = 0.03) but not mortality .We did a systematic search for pre-print and published trials in Medline, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) on the 22nd of September 2021. We included randomised trials that compared management with or without information from implanted haemodynamic monitoring devices for patients with heart failure. Outcomes selected were hospitalisation for heart failure and all-cause mortality. Changes in treatment associated with haemodynamic monitoring resulted in only a small reduction in mean pulmonary artery pressure , which generally remained much greater than 20 mmHg. Haemodynamic monitoring reduced hospitalisations for heart failure (HR 0.75; 95% CI 0.58–0.96; Haemodynamic monitoring for patients with heart failure may reduce the risk of hospitalization for heart failure but this has not yet translated into a reduction in mortality, perhaps because the duration of trials was too short or the reduction in pulmonary artery pressure was not sufficiently large. The efficacy and safety of aiming for larger reductions in pulmonary artery pressure should be explored.The online version contains supplementary material available at 10.1007/s00392-022-02104-0. Identifying, quantifying and treating congestion at an early stage is a key task for good management of heart failure, but it is currently done sub-optimally.Heart failure can be defined as cardiac dysfunction associated with interstitial or intravascular water and salt retention, otherwise known as congestion. Congestion is not only a cause of symptoms and signs but may also cause cardiac dysfunction, remodelling and arrhythmias, which are all associated with a poorer prognosis . IdentifSymptoms and signs have traditionally been used to guide therapy but are not specific for heart failure and may only be obvious once decompensation is severe . High plEchocardiography is not only widely available and frequently used for non-invasive, real-time assessment of cardiac structure and function but can also provide information on congestion. However, it requires expertise to acquire and interpret images, and there is little evidence, as yet, that serial ultrasound can be used to guide diuretic treatment. There is also a lack of robust evidence that other non-invasive approaches to estimate the amount of body water and its distribution, such as weighing scales, bio-impedance or remote dielectric sensing, improve management and outcomes for patients with heart failure .Elevated pulmonary artery (PA) or right ventricular pressures also reflect congestion and identify patients with heart failure who are at greater risk of hospitalization or death . RecentlIn this manuscript, we summarise the rationale and the current state-of-the-art of implanted haemodynamic monitoring devices for patients with heart failure. We also conducted a systematic review and meta-analysis of randomised trials to investigate the effects of this strategy on heart failure hospitalisations and mortality in this population.Recently, updated guidelines reduced the threshold for diagnosing PH from a mean PAP of 25 mmHg down to 20 mmHg, assessed at rest during a right heart catheterisation (RHC) . HoweverIn routine clinical practice, ultrasound is often used to identify PH, combining information from tricuspid regurgitation (TR) peak velocity and inferior vena cava diameter and collapsibility to estimate PA systolic pressure (PAPs) ; an echoPersistently elevated left atrial pressures, due to left ventricular dysfunction or mitral valve disease, are transmitted backwards to the pulmonary circulation, leading to a rise of pulmonary artery pressure (PAP) . At firsPH is common in patients with heart failure, but its reported prevalence depends on the criteria used to define it and the severity of heart failure –21. PerhPatients with PH generally have more severe heart failure, are older , 29 and The ESCAPE trial  investigP/dt) used to estimate the pulmonary artery diastolic (ePAPd) pressure that closely correlated with the pulmonary artery diastolic pressure (PAPd), measured invasively. A handheld radiofrequency wand, placed over the chest by the patient, interrogated the device and transmitted data remotely to healthcare professionals for review. Initially developed as a stand-alone device, the technology was subsequently incorporated into an implantable cardioverter defibrillator (ICD). The device measured pressures continuously but stored only a sample in memory that could be transmitted; this was usually the 8.5 min prior to each transmission. Patients could be instructed to rest or take exercise prior to transmitting data.The Chronicle device had a lead-mounted pressure sensor placed in the outflow tract of the RV. The lead was connected to a box, implanted subcutaneously in the pectoral area and containing the electronic components and power source. The pressure sensor used the principle of variable capacitance to provide measures of RV systolic and diastolic pressures and to assess the maximum rate of the pressure increase and decrease  technology and requires neither batteries nor leads. The sensor is 15-mm long and 3-mm wide and is permanently implanted in a distal branch of the PA via RHC. Two loops at the ends of the sensor serve as anchors and allow automatic sizing to the width of the vessel. The PA sensor consists of a three-dimensional coil and pressure sensitive capacitor. The coil electromagnetically couples the pressure sensitive capacitor to the electronics system, allowing the remote measurement of the resonant frequency then it is converted to a pressure measurement. Collection of haemodynamic data requires the patient to lie on an external pillow-like device which injects radiofrequency energy into the sensor, receives back signals to generate the waveform and transmits the data to a remote service facility that then relays the results to the patient’s healthcare providerCompared to the Chronicle device, CardioMEMS does not require a surgical implantation procedure with the entailed risks and complications; CardioMEMS also measures PA pressure directly. However, a potential limitation of CardioMEMS is the difficulty in capturing data during exercise. Assessing PA pressure during exercise might detect sub-optimal control of congestion at an earlier stage.In symptomatic patients with heart failure, monitoring of PAP using a wireless haemodynamic monitor system has been assigned a class IIb recommendation (level of evidence B) by the 2021 European Society of Cardiology (ESC) heart failure guidelines  in orderTo further evaluate the validity of these recommendations, we conducted a meta-analysis  after the publication of the largest trial to date, GUIDE-HF trial ., on the 22nd of September 2021, we searched Medline (PubMed), Embase (Ovid) and the Cochrane Central Register of Controlled Trials (CENTRAL) databases for randomised trials that investigated the use of implantable haemodynamic systems to monitor PAP in patients with heart failure.Our primary and secondary outcomes were total heart failure hospitalisations and all-cause mortality, respectively. Full methods are shown in the supplementary material. Brieflyn = 406), a further 4818 records were excluded by screening titles and abstracts; the remaining 431 articles were fully evaluated. We finally identified eight papers from four clinical trials: the CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients  [p = 0.03)   –41, the  papers) , 43, the papers)  and the  papers) . Figure 03) Fig. A, using 48) Fig. B.Fig. 1TConsidering the cost and complexity of haemodynamically guided monitoring for patients with heart failure, the results of randomised trial conducted, so far, are rather disappointing. Although haemodynamic monitoring might reduce hospitalisations for heart failure, the confidence intervals around the estimate are wide and the statistical certainty low. There are many potential explanations for why a reduction in hospitalisations and PA pressure might not translate into a reduction in mortality. Longer follow-up might be required for such small reductions in PA pressure to translate into reductions in mortality; more intense management to normalise PA pressure might lead to a greater reductions in hospitalisations and mortality but with the risk of more side effects. Perhaps the therapeutic algorithms are too cautious; perhaps current treatments are just not sufficiently effective , 46.In order to improve management of heart failure by haemodynamic monitoring, measurements should be accurate in order to avoid false alerts and detect true ones and must be followed by changes in management to correct the perceived problem (a low or a high PA pressure). The optimal target PAP may differ from one patient to the next. A too low pressure due to intensification of heart failure therapy may lead to a fall in cardiac output, systemic arterial pressures and renal function. Patient engagement is essential. Unless patients are given the correct advice and follow management recommendations, haemodynamic monitoring will not be of any help. There is a long ‘delivery chain’ including the sensor, the patient taking the measurement, transmission to the service centre, relay on to the care team, the formulation of recommendations by the care team, the transmission of those recommendations back to the patient and the patient acting on the advice. There is a lot that could go wrong: the chain is only as strong as its weakest link.n = 790 patients) suggests that only a substantial reduction in ePAPd during follow-up reduced mortality; however, a decrease of 3 mmHg, or more, between baseline and 6 months was observed in less than 20% of patients [In the COMPASS-HF  trial, hpatients –49.In CHAMPION , haemodyGUIDE-HF is the largest trial of haemodynamic monitoring conducted so far. By design, each patient was to be followed for only 12 months. Investigators were asked to contact participants twice a month for the first 3 months and then monthly until the end of the trial. Haemodynamic monitoring may provide less benefit when clinical care in the control group is frequent and of a high quality. Unfortunately, the COVID-19 pandemic struck when only about 40% of patients had completed 12 months of follow-up. An analysis  comparinThe rate of hospitalisation in CHAMPION and GUIDE-HF appears to be much higher, both in the intervention group and in the control arm, compared to many other landmark trials of heart failure . Differences in the characteristics of the population, in the design of the trial or the number of contacts between patients and physicians, during follow-up, both in the treatment and control arms, could explain the high rates of hospitalisation. Patients in GUIDE-HF may have been in a worse functional class than most other trials and had poorer renal function but they did not have a higher plasma NT-proBNP or annual mortality.Although many patients with elevated PAP must have been enrolled in landmark trials of beta-blockers and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACE-I/ARBs), the effects of these therapies on PAP have been rarely evaluated. In animal models, mineralocorticoid receptor antagonists improve RV function and reverse PH, but studies in patients with heart failure and PH are lacking . Indeed,Tran and colleagues  reportedp = 0.01).Sodium glucose cotransporter-2 inhibitors (SGLT2-Is) have recently been shown to be highly effective for the treatment of heart failure . In a siThe real-world clinical experience with CardioMEMS provides the opportunity to evaluate the combined effects of intensification of treatment on PAP in patients with heart failure but also the long-term safety of this approach. Using data from a post-approval registry of 1200 patients with severe heart failure symptoms implanted with CardioMEMS, Shavelle and colleagues  showed tThese findings replicate those previously reported by Heywood and colleagues , who useOf the 5,500 CardioMEMS implanted in the US during the first 3 years after FDA approval, the reported rate of adverse events was relatively low , including PA injury , 46 sensor malfunction or migration (1%), 15 (0.3%) bleeding or infection at the vascular access and 5 pulmonary embolism or device thrombosis . ExperieUncertainty remains about the cost-effectiveness of the CardioMEMS. Further research is required to estimate, more accurately, the financial sustainability at scale . WhetherTechnological developments now allow pulmonary artery pressure to be combined with other vital signs, to allow clinicians to individualise treatments with greater precision and without the need of clinical visits .Most of the circulating blood volume is contained in the highly compliant venous system, which might buffer the impact of an increased circulating volume on PAPm. The CardioMEMS device can measure PCWP, which reflect left atrial pressure, but it appears the snapshots that the device takes may be less reliable and therefore treatment recommendations are not based on them. Devices implanted in the atrial septum to measure left atrial pressure are being investigated . MonitorWe were only able to access to published information, and not to individual patient data, which precluded more detailed analysis. Additional limitations include the heterogeneity of the devices used in the trials and changes in practice and patient demographics over time ; patients in GUIDE-HF were, on average, a decade older than in CHAMPION (see supplementary Table S1).Monitoring pulmonary artery pressure in patients with heart failure reduces the risk of total heart failure hospitalisations, but not mortality. The results of our meta-analysis not only support recently updated professional guidelines but also highlight the need for further research before recommending widespread use of these currently costly technologies. Better patient selection, better patient engagement and education, better therapeutic algorithms, more ambitious haemodynamic targets and more effective and well-tolerated interventions to achieve them could yet make haemodynamic monitoring a cornerstone of care for patients with heart failure.Further research is required to implement these therapeutic strategies and to identify patients more likely to benefit, thereby justifying the additional costs.Supplementary file1 (DOCX 56 KB)Below is the link to the electronic supplementary material.


Double-inlet left ventricle (DILV) is most frequent among univentricular atrioventricular connections. In DILV, there is a single functioning ventricle, most commonly with left ventricular structure. This chamber receives both atrioventricular valves and is connected to an outlet chamber with morphologic features of the right ventricle. The great vessels are often transposed, and pulmonary stenosis is seen in two-thirds of patients. The anatomy and pathophysiology can be defined by echo-Doppler studies with a rare need for other imaging studies. The management is mostly related to the nature of associated heart defects and the degree of pathophysiological abnormality. When the infants present initially, treatment to address the hemodynamic issues is undertaken. Subsequently, these babies need staged total cavo-pulmonary connection, i.e., the Fontan procedure which is undertaken in three stages; these stages are described in this review. The existence of inter-stage mortality and post-Fontan complications is recognized and was reviewed. The paper concludes that DILV can be successfully diagnosed with echo-Doppler studies and this heart anomaly can be effectively treated with the currently prevailing medical, catheter interventional, and surgical treatment practices. The term univentricular heart was used to describe any heart defect with one (single) effective ventricular cavity. These heart defects are single ventricle, common ventricle, double-inlet left ventricle (DILV), and univentricular atrio-ventricular connections ,2,3. TheIn patients with DILV, the main ventricular cavity usually exhibits left ventricular morphology ,2,3. HowThe systemic and pulmonary venous return via the right and left atria, respectively, enter the single ventricle, and this admixture results in reduction in systemic arterial saturation in all patients with DILV ,2,3. ThiThe clinical presentation is mostly determined by the type and severity of associated heart defects, particularly, the severity of pulmonary outflow tract narrowing ,2,3. InfBabies without pulmonary stenosis typically manifest slightly later than those infants with severe pulmonary stenosis or atresia. They manifest with features of congestive heart failure in a few weeks or months after birth. If there is cyanosis, it is usually mild; this is secondary to large blood flow into the lungs. On precordial palpation, the cardiac impulses are increased and hyperdynamic. On auscultation, the cardiac sounds are generally within the normal range. An ejection systolic murmur of grade I to II/VI may be heard at the left sternal border. A mid-diastolic flow murmur at the apical region is auscultated if the pulmonary blood flow is increased. Findings suggestive of heart failure are not observed in the early newborn period but are seen in a few weeks or months later.Some of these babies may also be detected because of abnormal fetal echocardiographic studies or due to auscultation of a cardiac murmur in the newborn period. Or, they may have been detected because of pulse oximetry screening.Babies with associated aortic arch obstruction (interrupted aortic arch and aortic coarctation) present early with signs of shock and decreased systemic perfusion as and when the ductus arteriosus constricts.The chest roentgenographic features vary and largely depend on the quantity of pulmonary blood flow. Slight cardiac enlargement and reduced pulmonary blood flow are observed in children with substantial pulmonary outflow tract obstruction. Cardiomegaly of moderate to severe degree and augmented pulmonary blood flow are observed in infants without pulmonary stenosis. In infants with l-TGA, a prominent and straight left heart border may also be documented.1 and V2. In other patients, an Rs appearance is perceived in leads V5 and V6. Yet, some other patients may exhibit right, left, or bi-ventricular hypertrophy, largely dependent on the anatomic type. As mentioned above, none of the electrocardiographic abnormalities are characteristic for DILV.There are no electrocardiographic features that are diagnostic of DILV. In some patients, the electrocardiogram may demonstrate an atypical initial QRS vector with a qR pattern in leads VEcho-Doppler studies, in contrast to the chest X-ray and electrocardiographic findings, are very useful in coming up with a diagnosis and in characterizing pathophysiologic abnormality ,3. The lIn patients with TGA, the dimension of the BVF and signs of obstruction across this region should be examined. Obstruction at the BVF may either be seen at initial presentation, progress subsequently through the normal course of the disease, or may progress subsequent to the placement of the pulmonary artery band . Aortic Other studies such as computed tomography, magnetic resonance imaging, cardiac catheterization, and selective cineangiography are not needed since the echo-Doppler studies can define all anatomic and pathophysiologic issues related to DILV ,3. HowevChest X-rays and electrocardiograms are conventional studies performed for evaluation of all CHDs and are valuable in assessing the size of the heart, evaluating pulmonary blood flow and detecting pulmonary pathology, and in detecting arrhythmias. These studies, however, do not supply a diagnosis of the cardiac lesion. On the contrary, echocardiography and Doppler are helpful in coming up with the diagnosis and in assessing pathophysiologic abnormalities and can be performed bedside. Magnetic resonance imaging and computed tomography studies also provide diagnostic information similar to echo studies but require transportation of the baby to a radiology suite, sometimes needing anesthesia. However, these studies can provide information that is not available by echo alone. Cardiac catheterization with selective cineangiography is no longer performed routinely for diagnostic purposes.Attempts were made initially to insert a prosthetic ventricular septum within the single ventricle  and thesStage I is the treatment initiated when the baby presents for the first time, usually as a neonate or a young infant and is largely dependent on the pathophysiology of the defect complex and the associated heart defects. Status of blood flow to the pulmonary circuit and the existence of obstructive defects within or outside the heart determine the type of initial therapy.1 (PGE1); the recommended dose is 0.05–0.1 mcg/kg/min. Once the O2 saturations improve, the dosage of PGE1 is slowly, step-by-step, reduced to 0.02–0.025 mcg/kg/min in an attempt to decrease the adverse effects of PGE1. After the infant is stabilized, further diagnostic studies are performed as necessary. Then, a steadier method of perfusing the pulmonary circuit should be established. Several methods to increase pulmonary blood flow have been employed earlier, as discussed previously [Reduced pulmonary blood flow may be due to atresia or severe pulmonary outflow obstruction. In these babies, the ductus arteriosus must be kept patent by intravenous infusion of prostaglandin Eeviously . Among seviously , implanteviously ,20,21, aeviously ,23,24 areviously   performed early on, end-to-side joining the superior vena cava with the right pulmonary artery surgically, i.e., the bidirectional Glenn procedure  Figure , is perfIn children with persistent left superior vena cava, a bilateral bidirectional Glenn procedure  is accomBefore performing the bidirectional Glenn operation, one should ensure that the pulmonary artery pressures are within normal limits and that the branch pulmonary arteries are of acceptable size. This is to ensure adequate forward flow across the Glenn shunt since there is no pumping chamber. Such assessment was performed in the past with the use of cardiac catheterization and cine-angiographic studies. Recently, some institutions have been employing echocardiographic, magnetic resonance imaging, or computed tomography studies to achieve such assessment. If pulmonary arteries are stenosed, they may be treated with balloon dilatation or stent placement, as thought to be suitable. Alternatively, repair of pulmonary arteries may be performed while undertaking the bidirectional Glenn procedure. In children with one ventricle, the systemic and pulmonary circuits work in parallel in place of the normal in-series circulation and a subtle balance among the two circuits should be preserved in order to maintain satisfactory perfusion of both systemic and pulmonary circulations ,46. If sDuring the final Stage III, the blood from the inferior vena cava is rerouted into the pulmonary artery and a fenestration is created in between the conduit connecting the inferior vena cava with the pulmonary artery and the remaining atrial mass. The author arbitrarily separates the procedure into Stage IIIA, consisting of diversion of the inferior vena caval flow into the pulmonary artery and Stage IIIB during which the fenestration is occluded ,14.During the Stage IIIA, the TCPC is performed by conveying the inferior vena caval flow into the pulmonary artery either through a lateral tunnel method ,52 or byStage IIIB is usually undertaken 6–12 months after Stage IIIA of the Fontan surgery; the fenestration is generally occluded  by transSubsequent to Fontan completion, clinical follow-up in an outpatient setting is essential; it is recommended that the patients are assessed at 1-, 6-, and 12-months following Stage IIIB Fontan and yearly afterwards ,14,15. ISeveral complications were noticed during the follow-up of the Fontan patients and these include development of arrhythmias, onset of obstruction within the Fontan pathways, residual defects producing shunts, thrombus formation, embolism causing episodes of cerebro-vascular accidents or transient ischemic attacks, cyanosis due to right to left shunting, formation of collateral vessel connections between systemic and pulmonary venous circuits, systemic venous congestion, and protein-losing enteropathy ,13,61. FUniventricular hearts are rare complex CHDs and constitute less than 2% of all CHDs. DILV is the most common among univentricular atrioventricular connections and is discussed in this review. In this anomaly, there is one functioning ventricle which has left ventricular morphology (most of the cases), receives both atrioventricular valves, and gives origin to an outlet chamber with morphologic features of a right ventricle. The great vessels are frequently transposed and pulmonary stenosis is present in the majority of patients. Some of these patients have other obstructive lesions including BVF constriction and coarctation of the aorta. DILV and associated defects can be defined by echo-Doppler studies with occasional need for other imaging studies. Therapy is largely based on the type of associated cardiac defects and the degree of hemodynamic abnormality that they produce and were detailed in the review. These children are commonly treated with staged TCPC (Fontan) in three stages. Stages I provides palliation of the hemodynamic abnormalities detected at presentation, Stage II consists of the bidirectional Glenn procedure, and Stage III is TCPC with an extracardiac conduit with fenestration; the latter is subsequently closed by transcatheter methodology. The prevalence of inter-stage mortality is high (5% to 15%); it is more frequent between Stages I and II than between Stages II and III. The inter-stage mortality is largely related to: restrictive atrial communication; obstruction of the aortic arch; distortion/stenosis of the pulmonary arteries; atrioventricular valve insufficiency; shunt blockage; and inter-current illnesses. Intermittent clinical evaluation along with echo-Doppler or other imaging studies to identify these anomalies should be methodically pursued and when detected, they should be promptly addressed. Even minor inter-current illnesses must be treated aggressively. Periodic follow-up after the Fontan procedure while administering medications in some patients and vigilance to detect complications of the Fontan surgery is necessary. It was concluded that DILV can be successfully diagnosed with the currently available non-invasive techniques and the defect can effectively be managed with the presently available medical, catheter interventional, and surgical therapeutic methodologies.


The repeatability of T1 and T2 values over 6 measurements in the International Society for Magnetic Resonance in Medicine/National Institute of Standards and Technology MRI system phantom was assessed to demonstrate intrascanner variation. The reproducibility between the 4 clinical scanners was assessed to demonstrate interscanner variation. The same‐day test–retest normal prostate mean T1 and T2 values from peripheral zone and transitional zone were also compared using the intraclass correlation coefficient and Bland–Altman analysis.MRF experiments were performed on 5 different 3 Tesla MRI scanners at 3 different institutions: University Hospitals Cleveland Medical Center , Brigham and Women's Hospital  in the United States, and Diagnosticos da America  in Brazil. Raw MRF data were reconstructed using a Gadgetron‐based MRF online reconstruction pipeline to yield quantitative T1 and 4.7% for T2 for relaxation values, within the range of 307.7 to 2360 ms for T1 and 19.1 to 248.5 ms for T2. Interscanner measurements showed that the T1 variation was less than 4.9%, and T2 variation was less than 8.1% between multicenter scanners. Both T1 and T2 values in in vivo prostatic tissue demonstrated high test–retest reliability (intraclass correlation coefficient > 0.92) and strong linear correlation (R2 > 0.840).The intrascanner variation of values measured using MRF was less than 2% for T1 and T2 are repeatable and reproducible between MRI scanners at different centers on different continents for the above measurement ranges.Prostate MRF measurements of T Click here for author‐reader discussions MRFMR FingerprintingPZPeripheral ZoneTZTransition ZoneISMRM/NISTInternational Society for Magnetic Resonance in Medicine/National Institute of Standards and TechnologyUHCMCUniversity Hospitals Cleveland Medical CenterBWHBrigham and Women's HospitalDASADiagnosticos da AmericaSVDSingular Value DecompositionCVCoefficient of VariationCIConfidence IntervalPI‐RADSProstate Imaging Reporting And Data System11 and T2 measurements in the prostate.1 and T2 values can be used to differentiate between normal peripheral zone (PZ) and prostate cancer,MR fingerprinting (MRF)1 and T2 measurements are also repeatable over time,In order to translate and use MRF meaningfully in clinical practice, the quantitative tissue properties measured with MRF must be repeatable and reproducible.1 and T2 estimates based on the MRF technique using the International Society for Magnetic Resonance in Medicine/National Institute of Standards and Technology (ISMRM/NIST) MRI system phantomThe purpose of this study was to evaluate multicenter repeatability and reproducibility of T22.12; matrix 400 × 400; flip angles 3.38–50°; TR 11.2–14.2 ms; slice thickness 5 mm; 3000 TRs, acquisition time 39 s/slice. A delay time of 5 s was inserted between measurements to ensure sufficient magnetization recovery before beginning the next experiment for both phantom and in vivo studies.This Health Insurance Portability and Accountability Act–compliant study was approved by the local institutional review board, and written informed consent was obtained for all in vivo scans. Experiments were performed on 5 different 3 Tesla MRI scanners  with different software versions  in 3 different institutions: University Hospitals Cleveland Medical Center (UHCMC) and Brigham and Women's Hospital (BWH) in the United States, and Diagnosticos da America (DASA) in Brazil. An MRF–fast imaging with steady‐state precession acquisition designed for use in the prostate2.21 is expected to range between 1000 and 2500 ms, and the T2 between 20 and 300 ms for 3 Tesla systems.1 values of  and T2 values of , denoted by min:step:max (ms), were used to balance between matching accuracy and MRF dictionary size. The dictionary had a total of 5970 entries.In order to efficiently match each measured signal timecourse to the appropriate combination of tissue property values, a precalculated MRF dictionary, which can be used as a look‐up table, was generated using Bloch equation simulations in MatLab . In the prostate region, the T2.31 and T2 values for each voxel. The Gadgetron reconstruction took 17.8 s for each slice.All map reconstruction was performed using a Gadgetron MRF implementation,2.41 and T2 values measured using MRF was validated using the T2 layer of ISMRM/NIST MRI system phantom with T1 values between 307.7 and 2360 ms and T2 values between 19.1 and 248.5 ms. The phantom was placed in the magnet for at least 20 min before the acquisition to reduce any errors due to motion of the water making up the phantom. Six single‐slice MRF measurements were then collected, with a delay of 5 s between measurements, on all 5 scanners. Following this acquisition, data for the same‐day test–retest study were collected on the UHCMC Verio 1, UHCMC Verio 2, UHCMC Skyra, and DASA Verio. The phantom was moved out of the magnet and placed again in the magnet, again allowed to settle for at least 20 min, and another set of 6 single‐slice MRF acquisitions was collected. Neither B0 nor B1 maps were collected in this study. The results from the MRF measurements were compared to the reference values measured and reported by NIST.The accuracy of the T2.5In addition to the phantom study, in vivo experiments were performed in 24 patients with suspected prostate cancer . The protocol used was the same as that described for the phantom study, with the following exceptions: No settling time was required for the in vivo prostate measurements. Also, instead of single‐slice measurements, 2 sets of 2‐slice MRF measurements with no slice gaps were acquired to assess same‐day test–retest reliability. The patients were removed from the scanner and then repositioned between the 2 MRF acquisitions.2.61 and T2 values was assessed using the coefficient of variation (CV), defined as the ratio of the SD to the mean of 6 measurements and expressed as a percentage:1 and T2 values between the 4 clinical scanners were calculated to demonstrate interscanner variation:For the ISMRM/NIST MRI system phantom study, the mean and SD for each sphere were calculated from a circular region of interest (70 pixels in size with a radius of 4.7 mm) that was manually drawn on the maps. For repeatability, intrascanner variation of Tl.k.b., with 13 years of radiology experience) in maps from both scans for all patients. Note that the ROIs from patients (10 pixels in size) were drawn in normal appearing regions (PI‐RADS 1 or PI‐RADS 2) with no specific findings. Mean T1 and T2 values were calculated for each region of interest. The intraclass correlation coefficientFor the in vivo subjects, regions of interest in the PZ and TZ were drawn by a radiologist  with the reference values. The bias for each vial  for each of the 5 scanners, is shown in Supporting Figure The means of the 6 measurements obtained from the ISMRM/NIST MRI system phantom on 5 scanners at the 3 different medical institutions are presented in Figure 1 values between 307.7 and 2360.0 ms and T2 values between 19.1 and 248.5 ms, as calculated by dividing the SD of the 6 repeat measurements by the mean of the 6 measurements (expressed as a percentage). Figure 1 and T2. The T1 estimates had a variation of 0.2% to 2.0%, and T2 estimates had a variation of 0.0% to 4.7%, with the exception of the vial with a T2 value of 19.1 ms, which showed a variation of 8.9%. The interscanner CVs over all 6 measurements are shown in orange in Figure 1 variation of 2.3% to 4.9% for T1 values between 307.7 and 2360.0 ms and T2 variation of 2.3% to 8.1% for T2 values between 40.5 and 248.5 ms. The variation increased in spheres with T2 values of lower than 28.8 ms. The difference between interscanner variations of multiple measurements and the variation in a single measurement is less than 2%.Figure 1 and T2 values in the ISMRM/NIST MRI system phantom were above 0.99 between repeated measurements made on the UHCMC Verio 1, UHCMC Verio 2, UHCMC Skyra, and DASA Verio  for limits of agreement when difference in measurements was plotted against the mean of the measurements  and acceptable agreement . The T2 values from PZ and TZ also showed a strong linear correlation  and acceptable agreement  with corresponding plots presented in Figure The Bland–Altman analysis revealed that 24 of 24 PZ T41 and T2 measurements on 5 different 3T MRI scanners with different software versions in 3 different medical institutions. It also demonstrates the use of a Gadgetron‐based online MRF reconstruction to generate quantitative maps rapidly at the scanner. This implementation enabled the same MRF reconstruction to be used on 5 different MRI scanners in 3 different locations where the personnel had technical expertise ranging from minimal to advanced. Additionally, the improvement in the workflow made possible through the use of the online reconstruction meant that quantitative maps could be provided immediately to the radiologist for annotation and analysis. Coupled with the results demonstrating repeatability and reproducibility, this work paves the way for a Gadgetron‐based MRF framework for quantitative mapping of the prostate to be distributed and used with a variety of MRI scanners around the world.This study assesses the repeatability and reproducibility of prostate MRF‐derived T1 and T2 values found in the ISMRM/NIST system phantom, intrascanner MRF T1 and T2 estimates showed small variations over 6 measurements. The interscanner measurements showed larger T1 and T2 variations between scanners at different institutions, which is similar to the results reported in Ref.1 CV < 2.0% and T2 CV < 4.7%) and reproducibility (T1 CV < 4.9% and T2 CV < 8.1%) for MRF T1 and T2 values in the phantom are similar to the reported prostate apparent diffusion coefficient values. However, T2 values lower than 30 ms and higher than 300 ms demonstrated larger variation. An underestimation of very high T2 values (> 300 ms) in the phantom study was observed as compared to reference values in Figure 2 are not expected to be clinically relevant in the prostate because cancer and prostatitis have much shorter measured T2. The T2 step size in the MRF dictionary was set to 10 ms from 160 to 200 and 50 ms from 250 to 500 ms because such high values were not originally expected to be encountered in vivo. Finer dictionary step size and higher maximum T2 values in the dictionary may improve the accuracy of high T2 values. Similarly, the higher CV seen for vials with a T2 value below 30 ms likely relates to dictionary coarseness (5 ms at this range), which is a substantial fraction of the measured values. A finer dictionary with smaller step sizes could result in an improved test–retest agreement and a lower CV. Other factors that may increase systematic variation of the measured T1 and T2 values ; National Institute of Biomedical Imaging and Bioengineering (P41 EB 015898); National Institutes of Health ; Siemens Healthineers.Wei‐Ching Lo is an employee of Siemens Medical Solutions. No potential conflicts of interest were disclosed by the other authors.Figure S1 Percentage bias in MRF‐FISP T1 (a) and T2 (b) values measured on the UHCMC Verio 1, UHCMC Verio 2, UHCMC Skyra, DASA Verio, and BWH Verio using the ISMRM/NIST MRI system phantom. The MRF‐FISP T1 and T2 values are compared to the reference values measured and reported by NIST.Figure S2 Bland‐Altman plots comparing same‐day test‐retest measurements using the ISMRM/NIST MRI system phantom on UHCMC Verio 1 (a and b), UHCMC Verio 2 (c and d), UHCMC Skyra (e and f), and DASA Verio (g and h).Figure S3 Demonstrative T1 and T2 maps generated using MRF‐FISP in the prostate collected on the UHCMC Verio 1, UHCMC Verio 2, UHCMC Skyra, DASA Verio, and BWH Verio. Values in the two zones were measured from ROIs like these shown here as black circles in the PZ.Click here for additional data file.