Despite increasing attention in the cardiac anesthesiology literature, continuous measurement of right ventricular pressure using a pulmonary artery catheter has not been described in orthotopic liver transplantation, despite similarities in the anesthetic approach to the two populations. We describe our preliminary experience with this technique in orthotopic liver transplantation, and by combining various derived measures with trans-esophageal echocardiography, make some early observations regarding the response of these measures of right ventricular function during the procedure.In this case series, ten patients (five men and five women) undergoing orthotopic liver transplantation in our institution had their surgeries performed while monitored with a pulmonary artery catheter with continuous right ventricular port transduction and trans-esophageal echocardiography. We recorded various right ventricular waveform  and echocardiographic  and described their change relative to baseline at timepoints five minutes before and after portal vein reperfusion, immediately after hepatic artery reperfusion and on abdominal closure.Except for tricuspid annular plane systolic excursion at five minutes prior to reperfusion , no echocardiographic metric was statistically significantly different at any timepoint relative to baseline. In contrast, changes in right ventricular outflow tract gradient and right ventricular dP/dt were highly significant at multiple timepoints, generally peaking immediately before or after reperfusion before reducing, but not returning to baseline in the neohepatic phase. Nine of 10 participants in this series demonstrated a degree of dynamic right ventricular outflow tract obstruction, which met criteria for hemodynamic significance (> 25 mmHg) in two participants. These changes were not materially affected by cardiac index.Dynamic right ventricular outflow tract obstruction of varying severity appears common in patients undergoing orthotopic liver transplantation. These results are hypothesis generating and will form the basis of future prospective research. The surgical insult of orthotopic liver transplantation (OLT)–coupled with the consequences of end-stage liver disease–increase the potential for major blood loss and fluid shifts, making it a high-risk surgical procedure. Hemodynamic perturbation during OLT is common, particularly around the time of reperfusion. Such instability is associated with operative morbidity and mortality, and has an incidence of 12–77% depending on the case series reviewed ) or median (the corresponding interquartile range [IQR]) depending on normality. Statistical comparisons were performed comparing the mean  change in echocardiographic or waveform parameters at each time point  relative to the baseline. A linear effects model was chosen because our data featured repeated sampling and some missing data [Given the exploratory nature of this analysis, we did not undertake a formal sample size calculation. Instead, our arbitrary series size of 10 participants was determined ing data . The Kening data . ParametTen patients, comprising five men and five women, were monitored using the described technique. The median age of the study sample was 56.5 years (IQR 46.8–62.7 years). The median duration of the operation was 497 minutes (IQR 461–519 minutes), and the mean MELD score was 19 points (SD 11). Specific participant characteristics are shown in The results of the analysis for changes in echocardiographic parameters are shown in The analysis results for changes in waveform parameters are shown in The correction of dP/dt for other hemodynamic metrics–the RV systolic pressure , RV diastolic pressure  and heart rate—is shown in No patient in this study sustained any major complications, defined as PA rupture from PAC insertion or an esophageal  injury from TEE.Data outlining norepinephrine dose for each patient at each time point and total fluid volume and type administered over the course of each procedure are contained in This is the first prospective exploratory observational study investigating the effects of OLT on echocardiographic and pressure waveform metrics of RV function. These were assessed using predefined time points relevant to hemodynamic instability . While sHemodynamic instability is common during OLT (particularly around the time of reperfusion), and is multifactorial . The exiThe techniques employed by the aforementioned studies derived metrics of RV performance and right sided cardiac output indirectly, as opposed to the technique  employed in this study, which has the benefit of measuring RV hemodynamic parameters directly. While direct transduction of the RV waveform using a PAC with an appropriately positioned RV lumen is increasingly employed in cardiac anesthesiology , 24, it We acknowledge some limitations. Firstly, despite the prospective nature of this investigation, the small sample size means that the findings cannot be considered robust. However, it must be emphasized that the purpose of this study was not to definitively describe the functional response of the RV during OLT but to determine whether a confirmatory study was warranted and to inform the design of any larger confirmatory trial. Hence, irrespective of the high levels of statistical significance demonstrated in some metrics, all the results of this study are considered hypothesis generating rather than definitive. Secondly, maintenance of a stable RV pressure waveform could not be maintained in all patients for the duration of the OLT (as evidenced by the exclusion of data from Patient 1). It is hypothesized that the large fluid shifts that accompany this procedure can result in dynamic changes in RV size at various times during the procedure, and that despite the catheter position remaining constant during the procedure the position of the tricuspid annulus may not be as stable. Accordingly, if the RV lumen is located only a short distance beyond the valve , it may move between the right atrium and the RV, depending on the volume state of the chamber. This occurred despite a deliberate attempt to exclude shorter patients  from the study. Thirdly, the attending anesthesiologist was unblinded; that is, the anesthesiologist had access to the RV waveform. While the RV pressure waveform analysis is not routinely used in our center, there was no guarantee that a treating clinician has not acted on any abnormality observed , thereby altering some of the metrics recorded. Finally, the intravenous volume administered to the patients relative to each time point was not recorded, mainly because of the difficulty in determining the preload from this metric alone. Additionally, we did not obtain metrics that would have allowed the derivation of pulmonary vascular resistance . Routine wedging of the PAC balloon is not part of our routine practice due to the perceived risk of pulmonary artery rupture. However, such information would be of use to further delineate changes in the pulmonary vasculature over the course of OLT, and other authors may wish to consider including this measurement in future studies if (1) it is part of their routine practice; or (2) if participants are consented to this specific risk.This study records our preliminary experience using direct RV pressure monitoring and TEE to examine various measures of RV performance during OLT. Our exploratory statistical analysis suggests that certain waveform-derived metrics studied would be of use in further confirmatory work. Additionally, and unexpectedly, the results indicate that varying degrees of dynamic RVOT obstruction may be common in patients undergoing OLT, that this may worsen over the course of the procedure without a return to the baseline, and that is affected minimally by any change in cardiac index. It is hypothesized that decreased pulmonary vascular elastance due to end-stage liver disease and donor allograft reperfusion are potential drivers of this phenomenon, although confirmatory studies are required. Despite obtaining a high degree of statistical significance for this metric, the small sample size of this study prevents any definitive conclusions from being drawn. Larger prospective studies using these monitoring modalities are necessary to investigate these findings further to quantify the effects of OLT on RV function and potentially examine the contribution of RV dysfunction and dynamic RVOT obstruction to hemodynamic disturbance during OLT in more detail.S1 Appendix(DOCX)Click here for additional data file.S2 Appendix(XLSX)Click here for additional data file.


Background: The Global Registry of Acute Coronary Events (GRACE) risk score (GRS) is an established powerful model in predicting prognosis of patients with acute coronary syndrome. However, it does not contain pathophysiological biomarkers. Myeloperoxidase (MPO) and trimethylamine N-oxide (TMAO) are novel biomarkers of different pathophysiological processes of acute myocardial infarction, and each of them predicts risk of adverse clinical outcomes. We aimed to investigate whether the addition of MPO and TMAO could improve a GRS-based prediction model in patients with ST-segment elevation myocardial infarction (STEMI).Methods: A prospective cohort of 444 consecutive patients with STEMI who underwent primary percutaneous coronary intervention were enrolled in this study. Plasma levels of MPO and TMAO were measured using samples collected before the interventional procedure. GRS at admission was calculated. Death and nonfatal myocardial infarction were recorded as major adverse cardiac events (MACEs). Kaplan–Meier survival analysis with Cox proportional-hazards regression was used to identify predictive values of MPO and TMAO. Area under the receiver-operator characteristic curve (AUC) and net reclassification improvement (NRI) were calculated to evaluate the increment of predictive value for the combination of MPO and TMAO with GRS in predicting adverse clinical outcomes.Results: During 6 months follow-up, 27 patients suffered MACEs. Both MPO  and TMAO  predicted MACEs at 6 months. The AUC for MPO, TMAO, GRS, and their combination in predicting risk of MACEs at 6 months is 0.642, 0.692, 0.736, and 0.760, respectively. The addition of MPO and TMAO significantly improved the net reclassification of GRS for predicting MACEs at 6 months .Conclusion: Plasma MPO and TMAO each predict near-term risk of adverse outcomes in patients with STEMI. Furthermore, the combination of MPO and TMAO with GRS enables more accurate prediction of cardiovascular events compared with GRS alone. The Global Registry of Acute Coronary Events (GRACE) risk score (GRS) is a powerful model in predicting short- and long-term mortality and reinfarction after acute coronary syndrome (ACS). However, it does not contain biomarkers that reflect diverse pathophysiological processes of ACS patients.Myeloperoxidase (MPO) and trimethylamine N-oxide (TMAO) are novel biomarkers of different pathophysiological processes of acute myocardial infarction (AMI). Circulating MPO level is elevated in patients with plaque erosion compared with those with plaque rupture. . The sysIn this study, we investigated the value of MPO, TMAO, and their combination in predicting cardiovascular events in patients with ST-segment elevation myocardial infarction (STEMI). We further explored whether the addition of MPO and TMAO improve prediction ability of GRS for near-term outcomes in STEMI patients.Consecutive patients presenting with STEMI who underwent primary percutaneous coronary intervention at Fuwai Hospital were prospectively enrolled in this study cohort. STEMI was defined as continuous chest pain lasting >30 min, ST-segment elevation >0.1 mV in at least two contiguous leads or new left bundle branch block on 18-lead electrocardiogram, and an elevated troponin I level (cTnI ≥0.08 ng/ml) . Betweenvia radial or femoral access before the interventional procedure using vacutainer tubes containing ethylenediaminetetraacetic acid (EDTA). Samples were maintained at 4°C, processed within 3 h, and then stored at −80°C until further analysis. Plasma levels of TMAO were quantified by stable isotope dilution high-performance liquid chromatography with online electrospray ionization tandem mass spectrometry using an API 3200 triple quadrupole mass spectrometer  with a d9-(trimethyl)-labeled internal standard as described previously. (2) was calculated using the Modification of Diet in Renal Disease study equation , which included nonfatal MI or death. The secondary endpoint was death. Reviews of medical records and follow-up telephone interviews or clinical visits were conducted for 30-day and 6-month clinical outcomes. A 100% follow-up was achieved.Post hoc analyses were performed for continuous variables with a p value <0.05 between groups. Category variables were compared by the chi-squared test. Patients were divided into different groups according to median plasma level of MPO and/or TMAO. Kaplan–Meier curves were plotted to estimate the event-free survival between groups using the log-rank test. Cox proportional hazard regression analysis was used to determine hazard ratio (HR) and 95% confidence interval (CI) for adverse outcomes to MPO and TMAO as a continuous variable (log-transformed per SD increase). Adjustments were made for age, sex, smoking, hypertension, diabetes mellitus, eGFR, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Logistic regression analysis was used to generate predicted probabilities of MPO, TMAO, GRS, and their combination for predicting adverse outcomes. The incremental predictive ability from adding MPO and/or TMAO to GRS was analyzed from those predicted probabilities using increase in the area under the receiver operating characteristic curve (AUC) and category-free net reclassification improvement. . Categorical variables are presented as count (percentage). Continuous variables were compared using one-way analysis of variance and the Kruskal–Wallis test for parametric and nonparametric data, respectively. ovement. . StatistThe baseline characteristics of patients stratified according to median plasma levels of MPO (54.3 ng/ml) and TMAO (2.40 μM) are summarized in p = 0.017 and log-rank p = 0.049, respectively) and 6 months   but not at 30 days    . Cox regctively) . Howeverctively) .p = 0.004 and log-rank p = 0.002, respectively) and 6 months   and 6 months   and 6 months   . Cox regctively) . Howeverctively) .p < 0.001) (p = 0.005) and death  at 6 months (p = 0.017) (p = 0.096)  . Compare6 months . After a= 0.017) . However= 0.096) . Notablyp = 0.013), 0.692 , 0.736 , and 0.760  for predicting MACEs, and 0.675 , 0.724 , 0.837 , and 0.857  for predicting death at 6 months (p = 0.087) and death (p = 0.118) at 6 months (p = 0.032) and 0.67 (p = 0.005) (p = 0.022) and death  at 30 days  . The net 30 days .In this study, we demonstrate that plasma MPO and TMAO each is a univariate predictor of near-term clinical outcomes, including MACEs and death, in patients with STEMI. We further find that the combination of MPO and TMAO enhance the predictive value of MPO or TMAO alone. Moreover, the addition of MPO and TMAO to GRS can improve the ability of GRS alone in predicting near-term adverse events in STEMI patients.p value for MACEs (p = 0.056) and death (p = 0.062) remained marginally significant, and this might be attributed to the small sample size and short follow-up. Mechanical studies demonstrate that MPO can induce endothelial cell apoptosis and tissue factor expression (MPO, a hemoprotein stored in azurophilic granules of leukocytes and released on neutrophil activation, generates numerous reactive oxidants and diffusible radical species that are capable of initiating lipid peroxidation . A numbepression , which ain vivo study demonstrates that TMAO promotes platelet hyperreactivity and thrombosis risk by enhancing stimulus-dependent release of Ca2+ from intracellular Ca2+ stores (in vitro mechanistic studies indicate that TMAO can induce vascular inflammation and endothelial dysfunction through activating NLRP3 inflammasome and the mitogen-activated protein kinase/nuclear factor-kappa B pathway (TMAO, a metabolite generated by the gut microbiota from dietary nutrients rich in choline, phosphatidylcholine, and L-carnitine, is shown to be atherogenic . Numerou+ stores . Numerou+ stores . In addi pathway , which aDespite the advances in revascularization techniques, medical treatment, and risk factor modification, the prognosis of AMI remains poor , indicatGRS is an established powerful model of predicting prognosis for patients with ACS. However, it does not contain pathophysiologic variables, which could affect clinical outcomes of ACS patients. In this study, we investigate whether the addition of MPO and TMAO to GRS could improve the ability of GRS in predicting the prognosis of STEMI patients. Although the increments in AUC were not significant, the net reclassification analyses show that the combination of MPO and TMAO with GRS significantly improved the predictability of GRS alone for predicting near-term adverse events. It is not surprising that the increment in the AUC is not significant because ΔAUC provided by a new biomarker is overly conservative and depends on the performance of the underlying clinical model, which means that a powerful clinical model, such as GRS is difficult to improve . To dealThis study has several limitations. First, the predictive value of the combination of MPO and TMAO for long-term prognosis is not investigated because this is a contemporary study cohort. We aim to investigate this in future studies. Second, as this is a single center study, a multicenter validation cohort is needed to confirm our study results. Third, blood samples were collected at a single time point before emergency interventional procedures, and we did not have information about dietary history and prior antibiotic use for patients enrolled, which might have some impacts on plasma TMAO levels.High plasma levels of MPO and TMAO predict increased risk of near-term adverse clinical outcomes of patients with STEMI. The combination of MPO and TMAO could enhance the prediction ability of adverse events in STEMI patients when compared with MPO or TMAO alone. Moreover, the addition of MPO and TMAO could significantly improve the ability of GRS to predict near-term prognosis, suggesting a potential utility for the combination of MPO, TMAO, and GRS in improving risk stratification and clinical management of patients with AMI.


P = 0.006), CS  and RS  improved after revascularization of the CTO, albeit to a small, clinically irrelevant, extent. Strain improvement was inversely related to the extent of scar, even after correcting for baseline strain . In the vascular territory of the CTO, dysfunctional segments showed minor improvement in both CS  and RS  after PCI. Percutaneous revascularization of CTOs does not lead to a clinically relevant improvement of LV function, even in the subgroup of patients and segments most likely to benefit from revascularization .To evaluate the effect of percutaneous coronary intervention (PCI) of coronary chronic total occlusions (CTOs) on left ventricular (LV) strain assessed using cardiac magnetic resonance (CMR) tissue tracking. In 150 patients with a CTO, longitudinal (LS), radial (RS) and circumferential shortening (CS) were determined using CMR tissue tracking before and 3 months after successful PCI. In patients with impaired LV strain at baseline, global LS (10.9 ± 2.4% vs 11.6 ± 2.8%; The online version contains supplementary material available at 10.1007/s10554-021-02355-4. Coronary chronic total occlusions (CTOs) are present in approximately 1 in 4 patients with obstructive coronary artery disease (CAD) on invasive coronary angiography . ContempConsecutive patients with a CTO of a native coronary artery referred to the Amsterdam University Medical Center were prospectively enrolled between 2013 and 2018. CTO was defined as a vessel with Thrombolysis In Myocardial Infarction (TIMI) flow grade 0 or 1 with an estimated duration of ≥ 3 months. Baseline CMR was performed prior to CTO-PCI in all patients and follow-up CMR was scheduled 3 months after successful percutaneous revascularization. Exclusion criteria were recent myocardial infarction, concomitant non-ischemic cardiomyopathy and non-diagnostic baseline or follow-up CMR cine images. Since myocardial strain values are dependent on acquisition method and post-processing software, 100 healthy volunteers without a history of cardiovascular disease underwent CMR to calculate normal values. The study was approved by the Institutional Review Board of the Amsterdam University Medical Center, location VUmc. All subjects provided written informed consent.CMR was performed in all subjects on a 1.5-T clinical scanner  using identical imaging parameters. Cine images were obtained using a balanced steady-state free-precession sequence in the 2-, 3- and 4-chamber long-axis views and multiple short-axis views covering the entire LV from base to apex. Typical imaging parameters were: echo time, 1.5 ms; repetition time, 3.2 ms; α, 60 to 80°; spatial resolution, 1.6 × 1.6 mm; slice thickness, 5 mm; gap, 5 mm; temporal resolution, 30 to 50 ms. For assessment of myocardial scar, late gadolinium enhancement (LGE) images were obtained 10 to 15 min after administration of 0.2 mmol/kg of a gadolinium-based contrast agent  using a segmented inversion recovery gradient-echo pulse sequence. Slice positions of the LGE images were identical to those of the cine images. Typical imaging parameters were: echo time, 4.4 ms; repetition time, 9.6 ms; α, 25°; spatial resolution, 1.6 × 1.6 mm; slice thickness, 5 mm; inversion time, 250 to 350 ms.42 software . Endo- and epicardial contours were manually drawn on the end-diastolic and end-systolic phases and reference points for segmentation were manually defined at the anterior- and inferior RV insertion points. In line with prior reports, longitudinal and circumferential strain were expressed as absolute, positive values and the term shortening instead of strain was used  % before revascularization and increased to 5.0 [2.1 to 14.4] % after . Impaired global and radial strain were defined as LS < 14.4%, CS < 15.0% and RS < 22.1%.r = 0.86; P < 0.001 for GLS, r = 0.93; P < 0.001 for GCS, r = 0.90; P < 0.001 for GRS) and inversely with the extent of myocardial scar  . GLS was impaired in 62 (41%) patients, GCS in 60 (40%) patients and GRS in 58 (39%) patients. A total of 51 (34%) patients had impaired LV strain, defined as the combination of impaired GLS, GCS and GRS. Table P = 0.008 for GLS, B =  − 0.06; P = 0.016 for GCS, B =  − 0.13; P = 0.017 for GRS).GLS, GCS and GRS correlated strongly with LV ejection fraction . Table P = 0.37) and RS  was similar  CTO-PCI did not improve global longitudinal, circumferential and radial shortening; (2) CTO-PCI resulted in a small but significant improvement of global strain in patients with impaired LV function; (3) This improvement was primarily driven by strain recovery in dysfunctional myocardium in the vascular territory of the CTO.Previous CMR studies investigating functional improvement after CTO-PCI have shown conflicting results. While some studies reported an increase in LV ejection fraction after CTO-PCI, others found no improvement in LV function –19. InteIn the present study, functional recovery after CTO-PCI was investigated using myocardial strain indices rather than LV ejection fraction and analysis of wall thickening. LV ejection fraction is the cornerstone in the assessment of cardiac function, but is confounded by loading conditions and geometric factors such as LV wall thickness and cavity dimensions . AlthougSimilar to CMR tissue tracking, myocardial strain can also be assessed with echocardiography using a technique referred to as speckle tracking. Speckle tracking echocardiography is more widely available than CMR and has a higher spatial resolution. On the other hand, it has a lower signal-to-noise ratio and may be hampered by poor acoustic windows. Several studies have investigated the effects of CTO-PCI on LV function using speckle tracking echocardiography –33. AlthIn summary, LV function did not improve after CTO-PCI. Even in patients with LV dysfunction and myocardial viability at baseline, who are most likely to benefit from revascularization, the functional recovery that could be gained through CTO-PCI was only minor and not clinically relevant. It is therefore unlikely that CTO-PCI will reduce the incidence of heart failure or otherwise significantly improve prognosis for the individual patient through vast improvement of LV function. This should be taken into consideration when scheduling a patient for CTO-PCI, especially given the higher complication rate of CTO-PCI in comparison with regular PCI . CTO-PCIThe follow-up period of 3 months after successful PCI was arbitrary and longer follow-up may have increased the observed improvement in LV function. Moreover, CTO-PCI was not performed in patients without evidence of viability on baseline CMR. Although such a diagnostic work-up is advocated by current guidelines, the exclusion of patients with predominantly transmural scar in the CTO territory may explain the modest relationship between strain improvement and myocardial scar observed in the present study [Percutaneous revascularization of CTOs does not improve global longitudinal, circumferential or radial shortening. Even in the subgroup of patients and segments most likely to benefit from revascularization , CTO-PCI failed to show a clinically relevant improvement in myocardial contractility. It is therefore unlikely that CTO-PCI will favorably affect patient outcomes through recovery of LV function.Supplementary file1 (DOCX 1029 kb)Below is the link to the electronic supplementary material.


Rest/stress myocardial CT perfusion (CTP) has high diagnostic value for coronary artery disease (CAD), but the additional value of resting CTP especially dual-energy CTP (DE-CTP) beyond coronary CT angiography (CCTA) in chest pain triage remains unclear. We aimed to evaluate the diagnostic accuracy of resting myocardial DE-CTP, and additional value in detecting CAD beyond CCTA (obstructive stenosis: ≥ 50%) in patients suspected of CAD.13N-ammonia positron emission tomography (PET) as the gold standard. Diagnostic accuracy of cardiac dual-energy CT in detecting flow-limiting stenoses (justifying revascularization) by CCTA combined with resting myocardial DE-CTP, using ICA plus resting 13N-ammonia PET as the gold standard. The CCTA and DE-CTP datasets derived from a single-phase scan performed with dual-energy mode.In this prespecified subanalysis of 54 patients, we included patients suspected of CAD referred to invasive coronary angiography (ICA). Diagnostic accuracy of resting myocardial DE-CTP in detecting myocardial perfusion defects was assessed using resting 13N-ammonia PET.For detecting myocardial perfusion defects, DE-CTP demonstrated high diagnostic accuracy with a sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of 95.52%, 85.93%, and 0.907 on a per-segment basis. For detecting flow-limiting stenoses by CCTA alone, sensitivity, specificity, and AUC were 100%, 56.47%, and 0.777 respectively on a per-vessel basis. For detecting flow-limiting stenoses by CCTA combined with resting myocardial DE-CTP, sensitivity, specificity, and AUC were 96.10%, 95.29% and 0.956 respectively on a per-vessel basis. Additionally, CCTA combined with resting myocardial DE-CTP detected five patients (9%) with no obstructive stenosis but with myocardial perfusion defects confirmed by ICA plus Resting cardiac DE-CTP demonstrates a high diagnostic accuracy in detecting myocardial perfusion defects and provides an additional clinical value by reducing rates of false-positive and false-negative patients beyond CCTA in patients suspected of CAD. A comprehensive assessment of coronary artery disease (CAD) requires not only morphologic information about coronary artery stenosis but also functional evaluation about haemodynamic significance of coronary artery lesions –3. AlthoRecent single-center studies have shown good diagnostic performance of rest/stress myocardial CT perfusion (CTP) in detecting myocardial ischemia and infarct in both the acute and stable outpatient groups . But the13N-ammonia positron emission tomography (PET) and invasive coronary angiography (ICA) within one week time interval between examinations were enrolled. Patients were excluded if they had history of myocardial infarction, cardiomyopathy, myocarditis, contraindication to iodinated contrast agent, atrial fibrillation or renal dysfunction (estimated glomerular filtration rate < 60 ml/min/1.73 m2).Our study was approved by the institutional ethics committee, and the written informed consent was obtained from each patient. The study design was retrospective. Patients were recruited from an existing prospective study database consisting of consecutive patients suspected of CAD presenting with acute or stable chest pain to our hospital between March 2017 and November 2019. Patients who underwent cardiac dual-energy CT scan, resting 13N-ammonia (555 MBq) was injected. Tomographic images were reconstructed by the filtered back projection method. Typical horizontal long axis, vertical long axis, and short axis tomographic views of the left ventricle were obtained by an image processing workstation for image analysis.PET examinations were performed at rest on ECAT EXACT , which provide 47 tomographic slices. Patients abstained from food at least 6 h before the PET examination. Resting PET myocardial blood flow imaging was acquired 15 min after PET images were visually analyzed by 2 experienced readers who were blinded to the patient information. Horizontal long axis, vertical long axis, and short axis images were assessed on a per-segment and -territory basis using American Heart Association 17-segment model . The disICA was performed by standard catheterization in accordance with the American College of Cardiology Guidelines for Coronary Angiography . ICA wasAll CT examinations were performed at rest state using dual-energy mode of a 128-slice dual-source CT . Before the examination, the heart rate of each patient was measured. If the resting heart rate was higher than 65 beats per minute (bpm) and no contraindication to the use of β-blockers, metoprolol tartrate  was administered intravenously in fractions of 5–25 mg before the examination. Scanning parameters were as follows: 2 × 64 × 0.6 mm acquisition collimation with z-flying focal spot technique, and heart rate adaptive pitch of 0.17–0.35. Automated tube current modulation  was used. One tube of DSCT system was operated with 165 reference mAs per rotation at 100 kV, and the second tube was automatically operated with 140 reference mAs per rotation at 140 kV. All scans were performed in cranio-caudal direction of supine position during a mid-inspiratory breath-hold.The scanning range started from above the origin of the coronary arteries to below the dome of the diaphragm. Contrast agent was injected by a dual-syringe injector  using an 18-gauge intravenous needle placed in the right antecubital vein. A triphasic injection protocol was used . First, CCTA and resting myocardial DE-CTP were reconstructed from data of single arterial phase dual-energy CT scanning. The CCTA images were reconstructed with 0.75 mm slice thickness, 0.5 mm increment, 75 ms temporal resolution, and B26f kernel. All images were reconstructed by the same person to reduce bias. Then the reconstructed CCTA images were transferred to multi-modality work-place  and loaded into the Circulation application for further analysis.The DE-CTP images were reconstructed with 1.5 mm slice thickness, 1.0 mm increment, 280 ms temporal resolution, and a dedicated dual-energy convolution kernel (D30f). By default, raw data were automatically reconstructed into low-kilovoltage (100 kV) images and high-kilovoltage (140 kV) images. Then the 100 kV and 140 kV images were transferred to MMWP and loaded into dual-energy Heart PBV  to calculate the iodine distribution maps, with color-coded of “Hot Body 8 bit”. A normal myocardial area was chosen to normalize the iodine distribution maps .All dual-energy CT images were assessed on MMWP and patient information was removed. Images were assessed independently by two cardiac radiologists who were blinded to the patient information and disagreements were resolved by consensus. We performed separate readings of resting DE-CTP and CCTA. Readings were spaced at 2-week intervals to minimize recall bias.13N-ammonia PET as the gold standard.The DE-CTP images were visually analyzed on a per-segment -territory and -patient basis according to the American Heart Association 17-segment model . In colo13N-ammonia PET as the gold standard.CCTA images were analyzed for coronary obstructive stenosis ≥ 50% for each vessel  based on axial source images, cross-sectional views, multiplanar reformations, curved planar reformations and thin-slab maximum intensity projection images. The association between coronary artery distribution and myocardial segments was analyzed on the basis of the AHA recommendations . In viewP value < 0.05. Quantitative variables were expressed as mean value ± standard deviation. The diagnostic performance was calculated, including sensitivity, specificity, positive predictive value, negative predictive value, and accuracy with 95% confidence intervals. Additionally, the receiver operating characteristic (ROC) curve analysis was performed. The area under the ROC curves (AUCs) were compared by the DeLong method. Kappa tests were used to assess intra- and interobserver agreement in CCTA and resting myocardial DE-CTP analysis in 10 randomly selected patients. The Kappa value was interpreted as follows: 0–0.20 poor agreement, 0.21–0.40 fair agreement, 0.41–0.60 moderate agreement, 0.61–0.8 good agreement, and > 0.81 excellent agreement.Statistical analysis was performed using SAS version 9.1 , and the threshold of significance was 13N-ammonia is 1.11 mSv. Figure The characteristics of the study analytic population are summarized in Table A total number of 918 myocardial segments in 162 territories in 54 patients were analyzed. Diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and AUC of DE-CTP in detecting myocardial perfusion defects were 89.43%, 95.52%, 85.93%, 79.60%, 97.09%, and 0.907 respectively on per-segment basis; 91.98%, 97.56%, 86.25%, 87.91%, 97.18%, and 0.919 respectively on a per-territory basis; 94.44%, 100%, 82.35%, 92.50%, 100%, and 0.912 respectively on a per-patient basis  patients showed myocardial perfusion defects with no obstructive stenosis on CCTA combined with DE-CTP and were confirmed by ICA combined with k = 0.90, P < 0.001) and on a per-territory basis, and was "excellent" for CCTA  on a per-vessel basis.The inter-observer agreement was “excellent” for DE-CTP  which abnormal perfusion without obstructive stenosis (≥ 50%) . That isThe diagnostic work-up of patients suspected of CAD at presentation is typically oriented toward the detection of a hemodynamically relevant obstructive stenosis, which serves as the basis for further treatment decisions. However, a considerable number of patients who have angina and signs of ischemia at presentation do not have significant obstructive disease, obstructive stenosis as defined by 50% or greater diameter stenosis –24. AddiMoreover, DE-CTP derived iodine maps allow a quantitative analysis of myocardial iodine uptake in mg/ mL which is directly proportional to myocardial blood supply that are additive to routine single-energy CT, which mostly provides density-based information , 27. FutSeveral limitations of this study should be described here. First, an absolute quantitative approach was not used to determine the myocardial perfusion defects. Second, the relatively small number of patients included in this study limits the statistical power and strength of the conclusions. This reflects the logistical difficulties involved in carrying out multimodality imaging. Although small, the results are encouraging but need to be tested on a larger cohort. Third, in view of technical intermodality differences between dual-energy CT and PET in the higher spatial resolution , leading to slight differences in the visualisation of the transmurality of perfusion defects, we did non evaluate the transmurality of the perfusion defects. Fourth, ICA + PET is considered the gold standard in this study. Nevertheless, it should be acknowledged that ICA plus invasive fractional flow reserve (iFFR) is the unequivocal new gold standard for flow-limiting lesions.In this study, resting cardiac DE-CTP demonstrates a high diagnostic accuracy in detecting myocardial perfusion defects and provides an additional clinical value by reducing rates of false-positive and false-negative patients beyond CCTA in patients suspected of CAD. Future studies involving larger numbers of patients will be necessary for the validation of our findings.


Heart failure (HF) is the only cardiovascular disease with an ever increasing incidence. HF, through reduced functional capacity, frequent exacerbations of disease, and repeated hospitalizations, results in poorer quality of life, decreased work productivity, and significantly increased costs of the public health system. The main challenge in the treatment of HF is the availability of reliable prognostic models that would allow patients and doctors to develop realistic expectations about the prognosis and to choose the appropriate therapy and monitoring method. At this moment, there is a lack of universal parameters or scales on the basis of which we could easily capture the moment of deterioration of HF patients’ condition. Hence, it is crucial to identify such factors which at the same time will be widely available, cheap, and easy to use. We can find many studies showing different predictors of unfavorable outcome in HF patients: thorough assessment with echocardiography imaging, exercise testing , and biomarkers . Some of them are very promising, but more research is needed to create a specific panel on the basis of which we will be able to assess HF patients. At this moment despite identification of many markers of adverse outcomes, clinical decision-making in HF is still predominantly based on a few basic parameters, such as the presence of HF symptoms (NYHA class), left ventricular ejection fraction, and QRS complex duration and morphology. Heart failure (HF) is a cardiovascular disease with an ever increasing incidence . In the The main challenge in the treatment of HF is the availability of reliable prognostic models that would allow patients and doctors to develop realistic expectations about the prognosis and to choose the appropriate therapy and monitoring method. Prognosis assessment plays a special role in patients qualified for implantable device therapy or surgical treatment (including heart transplantation). Prognosis also plays an important role in planning terminal palliative care with the patient and his family. Not only does the predictor allow one to identify a high-risk patient in advance but it also allows one to monitor and implement individual preventive therapy. Secondly, identifying factors that contribute to poor prognosis can help develop new, targeted therapies . This arPredictors should be easily obtainable and associated with some therapeutic and clinical results .The 2016 European Society of Cardiology (ESC) guidelines on HF named over 70 predictors in HF patients . A modifThe 2019 ACC Expert Consensus Decision Pathway on Risk Assessment, Management, and Clinical Trajectory of Patients Hospitalized With Heart Failure also named many predictors of unfavorable outcome during hospitalization in HF patients . A modifHowever, no single risk factor is sufficient to predict prognosis in HF. Results of a few markers must be interpreted together. Still it is important to find the most important and valuable panel of a few predictors and there are still ongoing studies assessing potential new ones.Knowledge of a patient’s demographic, medical, and clinical data could play an important role in prediction of life expectancy. Previous studies have shown that male sex is more strongly associated with left ventricular systolic dysfunction, but female sex is more strongly associated with preserved left ventricular function –21. IschLow socioeconomic status in adulthood and childhood is associated with worsened HF outcomes –25. Low In the general population, increased systolic blood pressure (SBP) is associated with unfavorable outcomes and higher risk of development of HF. In the Framingham Heart Study population, 91% of the participants with HF had a previous diagnosis of hypertension . Compare2 increase in BMI) [p = 0.02), a reduction in left ventricular mass index (p < 0.0001), and improvement in left ventricular diastolic function (p ≤ 0.0001) [n = 11) [In the general population, increased body mass index (BMI) predisposes to development of HF (5% increase in risk for each 1 kg/m in BMI) , 38. In  0.0001) . However 0.0001)  and Fona 0.0001) . In the [n = 11) .The 2016 guidelines of the ESC identified cachexia and sarcopenia as important comorbidities of HF . CachexiThe New York Heart Association (NYHA) functional classification is still useful for assessing syndrome severity, patient’s exercise tolerance and prognosis in HF patients , 52. NYHA list of other significant values from the medical history and clinical status of the patient is presented in Tables Echocardiography provides detailed information regarding cardiac structure and function , 17. HFrThe CHARM trial  showed tMany echocardiographic markers have prognostic value in HF Fig. , and 3.FMechanical dyssynchrony (the late diastolic velocity (a′)) measured by tissue Doppler imaging (TDI) and LV dyssynchrony based on global longitudinal strain (GLS) imaging seem to be important prognostic markers in HFrEF . LocalizIn atrial fibrillation (AF) rhythm, the varying RR interval and changing loading conditions make it difficult to measure LV systolic function. A new method of correcting GLS by the RR seems to be an important marker for evaluation of LV systolic function in HFrEF patients with AF , 83.Left atrium (LA) volumes and function were the best echocardiographic markers of clinical outcomes  , as a seHowever, no single risk factor is sufficient to determine prognosis in HFrEF patients. The value of a few echocardiographic parameters must be interpreted together . Figure LVEF may be correct in HFpEF, even though systolic dysfunction is already appearing. The abnormal LV contraction includes abnormal longitudinal shortening  , 87, preMitral annular plane systolic excursion (MAPSE) has been suggested as a parameter for impaired longitudinal function and could provide complementary information to EF .GLS measured during bicycle ergometer testing has also been identified as an important prognostic marker in HFpEF .As already mentioned before, LA volumes and function are sensitive indicators of LV filling pressure . Strain Greater right ventricular (RV) afterload results in pulmonary hypertension (measured by tricuspid regurgitation (TR) velocity) and RV systolic dysfunction (measured by TAPSE) is highly prevalent in HFpEF . 2DS RV In summary, LV systolic and diastolic function, LA function, and RV function have prognostic value in HFpEF. Figure The 6-min walk test is useful in measuring functional limitation (patient’s exercise capacity) in the prognostic stratification and in evaluating the effects of therapy in children and adults with HF , 91. Hsi6MWT poorly correlates with hemodynamic and functional echocardiographic parameters . In the 6MWT distance can also be used to evaluate the effect of therapeutic interventions in patients with HF  . However2) defines maximum exercise capacity of the patient. CPET evaluation should start with maximum effort (RER > 1.0 to 1.1) [2 remains the gold standard in predicting outcome in HF. Peak VO2 < 14 ml/kg/min and < 12 ml/kg/min in patients on β-blockers, in the HFrEF population continues to be a significant prognostic factor. It is also an important predictor of death in HFpEF patients [2 should be interpreted as a percentage of predicted, with values < 50% indicating a poor prognosis [2 on effort and anaerobic threshold (AT) were used to determine the classification of the severity of HF  and a decrease in cardiac output (through the increased transpulmonary gradient).Cardiopulmonary exercise testing (CPET) through measurement of peak oxygen uptake (VO to 1.1) . Peak VOpatients , 107. Forognosis . Peak VOrognosis . Mean reFailure to achieve SBP > 120 mm Hg and no increase in SBP during exercise are associated with poor prognosis . Both ch2 slope and exercise oscillatory ventilation (EOV) are among the strongest predictors of poor outcome in HF. VE/VCO2 slope > 34 to 36 indicates high-risk HF patients [VE/VCOpatients . The prepatients .In summary, peak oxygen uptake parameters, ventilatory efficiency or stability, and chronotropic incompetence are the main CPET factors in predicting outcome in HF patients.2 for mortality risk stratification in HF patients [CPET is not often used in chronic HF patients for a few reasons, including the limited availability of equipment  and patient’s inability to perform a maximal effort test  , 115. Alpatients , PImax wMultiple impaired regulatory axes are seen in HF, including the renin-angiotensin-aldosterone system (RAAS), sympathetic regulation, neurohormonal regulation, and the cardiac stretch response. HF is associated with a chronic inflammatory state, oxidative stress, and in effect extracellular matrix remodeling . Many prNowadays, natriuretic peptides are the gold standard biomarkers . Brain nPrevious studies have shown different biomarker profiles between patients with HFrEF, heart failure with mid-range ejection fraction (HFmrEF), and HFpEF. For example, in the Tromp et al. study , HFmrEF In the Bielecka-Dabrowa et al. study , biomarkAccording to recent news, neutrophil gelatinase-associated lipocalin (NGAL), a marker of renal injury, seems to be also a good factor in the diagnosis and prognostic prediction in HF .Different miRNAs  could be increased in patients with HF . A recenHospitalization for HF within the last year has been significant risk factor of subsequent hospitalizations. The results of the QUALIFY survey showed that 30.4% of the patients had a history of at least two HF hospitalizations . In the Different risk models were constructed to assess different clinical endpoints in the HF population . Figure All of the presented models have shown only moderate probability in predicting death in HF . MoreoveCited studies allow for the isolation of variables included in the models more often than others: sex, age, SBP, HR, NYHA class, LVEF, BUN level, serum creatinine, and sodium concentration. Other strong prognostic factors of mortality in HF, consistently reported in different models, include BNP/NT-proBNP concentration, weight or body mass index, and diabetes mellitus , 135–147Despite the identification of many markers and models of poor prognosis, clinical decisions and guidelines in HF are still based mainly on several basic parameters, such as the presence of HF symptoms (NYHA class), LVEF, and the duration and morphology of the QRS complex . But con


Objective: To assess right ventricular (RV) function and RV-pulmonary arterial (PA) coupling by three-dimensions echocardiography and investigate the ability of RV-PA coupling to predict adverse clinical outcomes in patients with precapillary pulmonary hypertension (PH).Methods: We retrospectively collected a longitudinal cohort of 203 consecutive precapillary PH patients. RV volume, RV ejection fraction (RVEF), and RV longitudinal strain (RVLS) were quantitatively determined offline by 3D echocardiography. RV-PA coupling parameters including the RVEF/PA systolic pressure (PASP) ratio, pulmonary arterial compliance (PAC), and total pulmonary resistance (TPR) were recorded.Results: Over a median follow-up period of 20.9 months , 87 (42.9%) of 203 patients experienced adverse clinical outcomes. With increasing World Health Organization functional class (WHO-FC), significant trends were observed in increasing RV volume, decreasing RVEF, and worsening RVLS. RV arterial coupling (RVAC) and PAC were lower and TPR was higher for WHO-FC III+IV than WHO-FC I or II. The RVEF/PASP ratio showed a significant correlation with RVLS. RVAC had a stronger correlation with the RVEF/PASP ratio than other indices. Multivariate Cox proportional-hazard analysis identified a lower 3D RVEF and worse RVLS as strong predictors of adverse clinical events. RVAC, TPR, and PAC had varying degrees of predictive value, with optimal cutoff values of 0.74, 11.64, and 1.18, respectively.Conclusions: Precapillary-PH with RV-PA uncoupling as expressed by a RVEF/PASP ratio <0.44 was associated with adverse clinical outcomes. PAC decreased and TPR increased with increasing WHO-FC, with TPR showing better independent predictive value. Right ventricular (RV) adaptation to chronic pulmonary hypertensive (PH) syndromes is a significant determinant of long-term outcomes. RV failure is prognostic of adverse outcomes in patients with PH, and RV function is the most important prognostic determinant of survival in various forms of PH –3.RV adaptation to an increased PA load is a key determinant of outcomes in patients with precapillary PH . FurtherRight heart function and its coupling to pulmonary circulation play vital roles in the prognosis of PH. At present, pulmonary vascular resistance and compliance are two important indexes of PH in comprehensive clinical evaluation . PA compHowever, as we know, TAPSE, as only a one-dimensional parameter, cannot fully reflect the overall function of the RV. With the growing availability of three- dimensional (3D) imaging techniques such as magnetic resonance imaging (MRI) and 3D echocardiography (3DE), assessment of RV shape and functional changes has become more feasible. Three-dimensional modalities offer exceptional accuracy and reproducibility for the assessment of RV shape and function. With recent advances in 3DE, RV volumes measured by this technique can be used to evaluate RV-PA coupling. Specifically, 3DE can be used to measure RV shape and volume for the assessment of RV-PA coupling . MoreoveThis study was conducted according to the principles defined in the Declaration of Helsinki. The study protocol was approved by the Ethics Committee of Beijing Chao-yang Hospital. All participants in this study signed the written informed consent forms prior to the initiation of this study.This was a single-center, retrospective longitudinal cohort study consisting of consecutive precapillary PH patients treated from February 2014 to July 2019. Consecutive patients aged ≥18 years with a diagnosis of precapillary PH were included. Precapillary PH was defined by mPAP >20 mmHg, PAWP ≤ 15 mmHg and PVR >3 WU at rest as assessed by RHC . Patients underwent echocardiography, 6-min walk test and N-terminal pro-B-type natriuretic peptide (NT-proBNP) measurement within a 48-h interval. The WHO-FC for each patient was determined.The demographic and clinical characteristics of all patients included in the study were obtained through interviews and through inspection of the hospital database. The exclusion criteria included: incomplete clinical and catheter pressure recording data, atrial fibrillation, moderate or severe mitral or aortic valvular disease, and echocardiography imagines of poor quality. Initially, a total of 372 precapillary PH patients were registered. Among these patients, 101 cases did not have complete clinical or RHC recording; 21 patients had atrial fibrillation; and 6 had tricuspid valve prolapse. Another 13 patients had severe dilation of the RV leading to incomplete display and resulting in poor quality echocardiography imagines, and in 28 patients, the endocardium of the free wall of the RV was unclear. After application of the exclusion criteria, a total of 203 patients were finally included in this study .Images for the determination of RV volume were obtained with a Philips EPIQ 7C Doppler ultrasound machine  equipped with an X5-1 transducer (1–5 MHz). The RV-focused apical four-chamber (4Ch) dataset was obtained for a single breath-hold, and the electrocardiogram was gated over a maximum of 6 beats. Throughout the cardiac cycle scan, the entire RV cavity was within the scan volume. The optimized imaging depth and sector width were required to obtain the highest frame rate. The RV volume and function quantitative analyses were performed offline using the new ML approach  for data management. The resulting dynamic surface model could optionally be adjusted in end-diastole (ED) or end-systolic (ES). In the View Adjustment workflow step, the user could manually adjust the image landmarks. Accordingly, a RV-focused four-chamber view and a short-axis view were derived by the system. Also, the heart cycle to be analyzed could be changed in this state. According to the software guidelines, RV 3D dynamic surface models were generated, from which end-diastolic volume (EDV) and end-systolic volume (ESV) were obtained and stroke volume (SV) was calculated as: SV = EDV–ESV  15)..15).The following echocardiographic RV structural parameters were recorded: RV end-diastolic volume, RV end-diastolic volume indexed to body surface area (BSA), RV end-systolic volume, RV end-systolic volume indexed to BSA, RV basal diameter, RV mid-diameter, RV longitudinal diameter, RV basal diameter/LV basal diameter, and LV end-diastolic eccentricity index. Pericardial effusion was also be recorded.RV function was evaluated based on the 2015 American Society of Echocardiography guidelines for cardiac chamber quantification by echocardiography in adults , includiRV-PA coupling was assessed according to the Ees/Ea ratio. Ees represents RV contractility, and Ea represents RV afterload. RV-PA coupling is represented by Ees/Ea. RV Ees was determined as follows: Ees = RV ESP/ESVI . Ea was Pulmonary arterial compliance (PAC) was calculated as SV divided by PA pulse pressure (SV/systolic-diastolic PAP) (mL/mm Hg). Total pulmonary resistance (TPR) was calculated as mPAP/CO . SV was A Swan-Ganz thermodilution catheter  was inserted into the right inferior PA by experienced physicians (Drs. Wang JF and Huang Q). The following parameters were measured under stable hemodynamics: RA pressure, mPAP, pulmonary vascular resistance, and CI. Pulmonary vascular resistance (PVR) in Wood units (WU) was calculated using the equation: PVR = (mPAP – PAWP)/CO. Echocardiography and RHC were performed with an interval of <72 h for all patients.Clinical outcomes were analyzed in all precapillary PH patients according to pre-defined adverse clinical events. Adverse clinical events were defined as: (i) PH-related hospitalization with RV function deterioration, (ii) deterioration of PH requires further interventional or surgical treatment, including pulmonary endarterectomy and/or balloon pulmonary angioplasty, or (iii) death. The cause of death or hospitalization was adjudicated by the authors (Drs. Yang YH and Gong JN), after a review of the relevant medical history and related documentation. All patients were followed up until occurrence of clinical events or the end of the study period.t-test was used to identify significant between-group differences in normally distributed data. The relationships between RVEF and other clinical and echocardiographic variables were assessed using Pearson's or Spearman's correlation coefficients. Continuous variables were compared across the three cohorts using one-way analysis of variance (ANOVA) for quantitative variables and Chi square tests or exact Fisher Tests for categorical variables.All statistical analyses were conducted using SPSS version 23  and MedCalc 16.1 . The one-sample Kolmogorov-Smirnov test was used to determine the normal distribution of all data. The continuous variables are presented as mean ± standard deviation (SD), while categorical variables are presented as absolute numbers and percentages. The independent sample P < 0.10 on the univariate analysis as well as previously described prognostic parameters. Survival receiver operating characteristic (ROC) curves were constructed for the assessment of the sensitivity and specificity of the used predictors for the prediction of adverse clinical events. The optimal cut-off values for predicting survival were calculated using Youden's index method. Kaplan–Meier analysis was implemented, dividing patients according to RV function and RV-PA coupling indexes.The associations between variables and the combined clinical end point were tested using univariate Cox proportional-hazards analysis, with results presented as hazard ratios (HRs) and two-sided 95% confidence intervals (CIs). Multivariate survival analysis included all variables with a P < 0.05.To assess the magnitude of the variability caused by the manual corrections, an intra- and inter-reader variability analysis was conducted. Variability was expressed in terms of coefficients of variation (CoVs), calculated as the absolute difference between the corresponding pairs of repeated measurements as a percentage of their mean, and intraclass correlation coefficients (ICCs). Statistical significance was defined as a two-sided A total of 203 patients  with precapillary PH were enrolled and divided into three groups according to WHO-FC . The WHOP = 0.016 and P < 0.001, respectively) and ESV  values significantly greater than those in patients in the WHO-FC I and II groups. A higher RV volume and RV basal and mid-diameters with worse RV systolic function accounted for RV afterload, while no statistical difference in RV longitudinal diameter was observed (P = 0.949). RV functional parameters showed progressive deterioration of the RV with worsening WHO-FC. RVEF, TAPSE, RV FAC, and S′ were lower and RVLS was worse in the WHO-FC III+IV group than in the WHO-FC I and II groups. Across the WHO-FC stages, significant trends were observed for higher RV volume, lower RVEF, and worsened RVLS.RV dilatation was found to be higher in patients with precapillary PH with worsening WHO-FC. The results in P < 0.001), and the difference in the RVEF/PASP ratio was significant between patients with WHO-FC I and WHO-FC II (P < 0.031). RVAC and PAC also differed significantly among the WHO-FCs (P < 0.001). The TPR was found to be higher for WHO-FC III+IV than for WHO-FC I and II , and no significant difference in TPR was observed between the WHO-FC I and II groups (P = 0.058).The RVAC and PAC were found to be lower and the TPR was higher in patients with precapillary PH with worsening WHO-FC stage. RV-PA coupling, as assessed by the RVEF/PASP ratio, was found to be lower in patients with precapillary PH with worsening WHO-FC, showing a decline across the WHO-FC stages consistent with worsening RV systolic function accounting for RV afterload. The results in r = 0.701; P < 0.001). The correlations between the RVEF/PASP and TAPSE/PASP ratios and RV contractile function and its coupling to pulmonary circulation indices were similar, with no statistically significant differences.P = 0.001 and HR, 1.047; 95% CI, 1.001–1.096; P = 0.046, respectively). Another multivariate predictor of clinical worsening was TPR  after adjustment for age, sex and BSA. The RVEF/PASP ratio did not show significant predictive value , with optimal cutoff values of 0.74, 11.64, and 1.18, respectively.The calculated optimal cutoff values for the most significant parameters are presented in We next assessed the manual correction reproducibility of RVEDV, RVESV, and RVEF using Bland-Altman analysis. The intra-observer variability for RVEDV was −3.04 ± 5.39 , and the inter-observer variability was −3.65 ± 6.36 . The intra-observer variability for RVESV was −2.21 ± 3.58 , and the inter-observer variability was −2.20 ± 4.25 . The intra-observer variability for RVEF was 0.14 ± 0.83 , and the inter-observer variability was −0.02 ± 1.06 .In the present study, we quantified RV function and RV-PA coupling in precapillary PH patients, and our results provide insights based on 3D echocardiographic non-invasive measurement into potential predictors of RV dysfunction and RV coupling to the pulmonary circulation as well as their associations with patient prognosis. First, we observed that RV systolic function declined progressively within advancing WHO-FC, and 3D RVEF and RVLS demonstrated strong independent predictive value. Second, precapillary-PH in our study with a RVEF/PASP ratio <0.44 was associated with adverse clinical outcomes. Third, PAC decreased and TPR increased with advancing WHO-FC, with TPR showing the best independent predictive value.Chronic RV failure occurs in four distinct stages due to alterations in preload; changes in RV mechanics, and/or contractility; or increases in afterload . RV malaWe were able to evaluate RV-PA coupling performance relative to the RVEF/PASP ratio derived from 3DE. From the perspective of physiology and clinical treatment, it is very important and necessary to analyze the cardiopulmonary unit as a system. RV adaptability to PH depends on the ability of the RV to respond to increased afterload and increase its contractility. RVAC refers to the relationship between ventricular contractility and afterload, and the most objective index is the ratio of ventricular elasticity to arterial elasticity . A 2018 Compared to TAPSE as a single measure, TAPSE/PASP shows more pronounced differences in pediatric PH with different NYHA FC/modified ROSS score values . Tello ePAC was considered as an increase in blood volume in the arterial system, which produces a unit increase in arterial transmural pressure. We demonstrated that PAC decreased and TPR increased with advancing WHO-FC in the present study. PAC depends on the volume of the reservoir and on the elastic properties of the PA, as determined by the wall content and mPAP . A signiPmax was not calculated from measurements in the RHC procedure, and mPAP was used as a surrogate for RV ESP. Recent studies have shown that using mPAP as an alternative to RVESP may not be the best approach in RV–arterial coupling in severe PAH and have suggested that evaluating RVESP is best computed with modified equations . There were differences in treatment options between patients, which may have biased the patients' prognosis. RV Ees was obtained by RHC and was determined using the single-beat method . We calcquations .A progressive increase in afterload causes RV dysfunction in patients with precapillary PH, and 3D RVEF and RVLS demonstrated strong independent predictive value. RV-PA coupling, assessed according to the RVEF/PASP ratio, declined with advancing WHO-FC, consistent with worse RV systolic function accounting for RV afterload. Precapillary-PH with RV-PA uncoupling as expressed by a RVEF/PASP ratio <0.44 was associated with adverse clinical outcomes. TPR increased with advancing WHO-FC stage and showed independent predictive value.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee of Beijing Chao-yang Hospital. The patients/participants provided their written informed consent to participate in this study.YL designed the study and drafted and wrote the manuscript. All clinical characteristics and laboratory data at baseline were obtained from standardized clinical data by YY and JG. RHC were performed JW and QH. YL, DG, XZ, HH, and ZJ collected and analyzed the data. DG and SY drafted and wrote the manuscript. YL, XL, and YY revised the manuscript critically for intellectual content. All authors gave intellectual input to the study and approved the final version of the manuscript.SY was employed by the company Philips (China) Investment Co. Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


The DHM software is feasible, accurate, and quick in a large series of unselected patients, including those with suboptimal 2D images or in atrial fibrillation. We aimed to evaluate the feasibility and accuracy of machine learning-based automated dynamic quantification of left ventricular (LV) and left atrial (LA) volumes in an unselected population. We enrolled 600 unselected patients  clinically referred for transthoracic echocardiography (2DTTE), who also underwent 3D echocardiography (3DE) imaging. LV ejection fraction (EF), LV, and LA volumes were obtained from 2D images; 3D images were analyzed using dynamic heart model (DHM) software (Philips) resulting in LV and LA volume–time curves. A subgroup of 140 patients also underwent cardiac magnetic resonance (CMR) imaging. Average time of analysis, feasibility, and image quality were recorded, and results were compared between 2DTTE, DHM, and CMR. The use of DHM was feasible in 522/600 cases (87%). When feasible, the boundary position was considered accurate in 335/522 patients (64%), while major (n = 38) or minor (n = 149) border corrections were needed. The overall time required for DHM datasets was approximately 40 seconds. As expected, DHM LV volumes were larger than 2D ones , while no differences were found for LV EF and LA volumes . The comparison between DHM and CMR values showed a high correlation for LV volumes (r = 0.70 and r = 0.82,  An accurate and reproducible quantitative assessment of the left heart chamber’s size and function is pivotal for the diagnosis, treatment, and prognosis of heart diseases. In this regard, the most important contribution of 3D transthoracic echocardiography (3DE) is left ventricular (LV) and left atrial (LA) quantification.Recent development of artificial intelligence approaches, such as machine learning (ML) algorithms, has resulted in a 3D analysis technique that automatically detects LV and LA boundaries and allows fast, accurate, automated measurements of chamber volumes and function. While several studies have validated the “static” heart model (HM) , more reThe aims of our study were: (a) to evaluate the feasibility of the new DHM software in a large group of unselected patients with a wide range of acoustic windows, irrespective of heart rhythm; (b) to evaluate the relationship between image quality and accuracy of the detection of LV and LA boundaries; (c) to compare 2D echocardiography and DHM-derived LV and LA volumes and function and in a subgroup of cases to cardiac magnetic resonance (CMR) reference values.A total of 600 patients  referred for TTE were prospectively enrolled in this study from January 2019 to February 2020. All subjects underwent a complete 2D and 3D TTE. Moreover, 140 patients also underwent CMR for diagnostic reasons. The overall population included 40 patients with normal hearts, 312 patients with valve disease, 58 with coronary artery disease, 113 with dilated cardiomyopathy, and 77 patients with other miscellaneous pathologies (including 6 with hypertrophic cardiomyopathy). The study protocol complied with the ethical guidelines of the 1975 Declaration of Helsinki and was approved by our institutional review board. Informed consent was obtained from each patient.All echocardiographic examinations were performed using a Philips EPIQ echocardiographic system  equipped with an X5-1 transducer. LV end-diastolic volume (EDV), LV end-systolic volume (ESV), LV ejection fraction (EF) and LA volumes were measured from the 4- and 2-chamber views using the biplane Simpson’s method according to international guidelines.Following 2D echocardiographic (2DE) imaging, 3D full-volume acquisitions were obtained with the same probe from the 4-chamber apical view with the LV and LA properly centered along the major axis, as previously described . Before Briefly, 3D datasets were acquired in a single beat during a breath hold lasting a few seconds, ensuring optimal temporal and spatial resolution. The volumetric datasets were immediately evaluated on-board using the DHM software , which automatically identifies LV endo- and epi-cardial borders at end-diastole and LA borders at end-systole, allowing prompt quantification of the volumes of these chambers . In our CMR imaging was performed using a 1.5-T scanner  within 7 days from the echocardiographic examination to ensure that identical hemodynamic conditions were not made during changes in therapeutic regimens. All studies were carried out using dedicated cardiac software, phased-array surface receiver coils, and electrocardiogram triggering. Breath-hold steady-state free-precession cine imaging was performed in long- and short-axis orientations. A stack of short-axis slices encompassing right and left chambers from base to apex was used for ventricular and atrial volumes and systolic function assessment. CMR datasets were transferred to a dedicated workstation and analyzed with a cardiac software . LVEDV, LVESV, LVEF, and LA volume were evaluated on cine images according to the recommendations of the Society of Cardiovascular Magnetic Resonance .To assess the reproducibility of DHM measurements, intraobserver and interobserver variability were evaluated in a subset of 15 randomly selected patients. Physicians were blinded to the original LA, LV, and EF results.To derive interobserver variability, one physician was asked to recalculate DHM acquisition for 15 patient datasets after 4 weeks. Two investigators (G.I and V.M.) were asked to perform these measurements twice to assess intraobserver variability. The same loops were re-analyzed 2 weeks later by the two investigators who were blinded to all previous measurements. These investigators repeated the analysis with and without contour adjustments.p-values < 0.05. Statistical analysis was performed using SPSS 25 .Results are presented as mean ± standard deviation (SD). Volumes and LVEF data obtained with the DHM were compared with 2D and CMR values by using linear regression analysis with Pearson’s correlation coefficients. Moreover, Bland–Altman analysis was applied to evaluate the inter-technique agreement by calculating the bias (mean difference) and the 95% limits of agreement (defined as 1.96 SD around the mean difference). To assess the association between the categorical variables, a chi-square test was applied. Differences were considered significant with n = 327), suboptimal (n = 195), and poor (n = 78). The average time needed for DHM acquisition and analysis was 41 ± 12 seconds using automated software with manual corrections as needed. Seventy-three patients showed irregular rhythms at examination time, secondary to atrial fibrillation (p = 0.13) due to incorrect border identification, especially in extremely dilated cavities. Baseline characteristics of the study patients are summarized in illation . Need for = 0.94, p < 0.001, LVESV: r = 0.96, p < 0.001) showing excellent agreement. The automated algorithm resulted in minimal differences for LVEF, reflected by a minimum negative bias of 1.2% (p = 0.023) and DHM and MRI. of 1.2% . No signr = 0.70, p < 0.001; LVESV: r = 0.82, p<0.001) with a reasonable bias for LV volumes due to DHM underestimation with a good correlation for LVEF  with a slight overestimation by the automated algorithm with a narrow bias of 2.0%. Correlations between DHM and CMR for LA volumes were high with minimal bias.This is the first study to test the feasibility and accuracy of this automated software in a large, unselected population. The main findings of this study are as follows: 1) the dynamic heart model automated measurement of LV and LA volumes and function is highly feasible in a large, unselected population, and analysis duration is very short; 2) independent from pathologies and heart rhythm, the quality of DHM images is good, with only a minority of cases requiring major manual adjustment of boundaries; 3) DHM LV volume values had good agreement with biplane 2D measurements despite an overestimation of both diastolic and systolic LV volumes, and the same is true in terms of the correlation between DHM values vs. CMR with a DHM underestimation of LV volumes; (4) LVEF correlation among the three techniques was very high; (5) measurements of LA volumes by DHM showed excellent agreement with CMR volumes. Several studies validated the heart model-automated measurements of LV and LA volumes  the dyna,8, and o independ DHM LV vIn this study, we found that DHM was highly feasible and rapid (about 40 seconds) in 600 unselected cases, and the quality of data was good in patients with a variety of pathologies and cardiac rhythms, such as atrial fibrillation requiring no or only minor boundary adjustments in the large majority 94%) of patients. DHM feasibility in the entire non-selected population was 87%, similar to previous studies with ML-based techniques 4% of pat,11. IndeManual editing of the automatically detected LV endocardial surfaces is possible when the operator judges that the automatically detected surface is incorrect. According to our experience, manual border corrections are required in patients with suboptimal acoustic windows and in patients with pathologies in which anatomical deformation made automated endocardial tracking more complicated, such as dilated cardiomyopathy and hypertrophic cardiomyopathy. In these cases, minimal modifications of automated cardiac boundaries provide accurate volumetric analysis compared to both the gold-standard CMR reference and the conventional 2D echocardiography. An important advantage of automated software is that operator training is not required. Small adjustments of cardiac boundaries require less expertise than tracing the boundaries manually in conventional echocardiography. Furthermore, our results show excellent reproducibility of this approach, as expected for an automated technique, and results in significant time saving compared to the conventional analysis.Even though the accuracy of LV and LA functional curves was beyond the scope of our study, in the quality score, we included the plausibility of curves, and examples in our series clearly show that the systolic and diastolic phases of LV and LA curves are well defined. Specifically, in sinus rhythm and atrial fibrillation, patterns and profiles of LV and LA volume curves identify the presence or absence of atrial contraction . Normal With regards to feasibility, quality, and the percentage of major or minor adjustments, in normal subjects, valvular heart disease and coronary artery disease showed similar good DHM quality and need for minor adjustments. On the contrary, in dilated cardiomyopathy and miscellaneous pathologies, manual minor or major adjustments were needed in approximatively 60% of the cases. This observation is in agreement with previous data showing that the accuracy of HM volumes was lower in some pathologies because of incorrect detection of LV endocardium. Specifically, in some cases, the automatic detection of LV and LA borders may lead to the incorrect identification of the atrioventricular junction , or very dilated LV in which the apical and antero-lateral endocardium is not perfectly identified. Regarding patients with atrial fibrillation, the percentage of good images or minor adjustment was low (48%) despite high feasibility (81%).Measurements of 2D biplane standard LV and LA volume versus 3D DHM showed good agreement as demonstrated in previous studies ,13. All LA size and function parameters are associated with adverse outcomes in multiple disease states. Recent data suggest that the phasic LA function also holds prognostic information ,19,20,21Despite the demonstrated benefits of 3DE over 2D TTE , widesprTsang et al.  first deThe use of automated analysis software significantly reduced the time required to obtain LVEF, LV, and LA volumes with excellent reproducibility. As shown in Machine learning software requires a high-quality 3D dataset, thus restraining its application in patients with inadequate TTE windows. Although the use of the DHM algorithm showed high feasibility of left chamber analysis, automated border detection was difficult in some of the datasets. With 3DE imaging, specifically in single-beat acquisitions, low-frame-rate datasets may miss the true end-systolic frame. Despite the attempt to maximize frame rates, it was not always possible to ensure that it was sufficiently high to avoid this pitfall.Our findings confirm that incorporating DHM into daily practice is a promising way to overcome challenges associated with the previous 3D clinical workflow.


Our clinical case supports the effectiveness of distal His‐Bundle pacing in obtaining ventricular resynchronization in patients with LBBB and left ventricular dysfunction, particularly in the context of post‐TAVI conduction disturbances. Our clinical case supports the effectiveness of distal His‐Bundle pacing in obtaining ventricular resynchronization in patients with LBBB and left ventricular dysfunction, particularly in the context of post‐TAVI conduction disturbances. New‐onset conduction disturbances with need for permanent pacing are relatively common after TAVI. We report a case of a permanent pacemaker implantation in a patient with (previous) left bundle branch block (LBBB), left ventricular ejection fraction (LVEF) of 32%, and high degree atrioventricular block (AVB) induced after TAVI, with His‐bundle capture resulting in the correction of the LBBB and LVEF improvement in the early postoperative period.Surgical aortic valve replacement has been the gold standard treatment for severe aortic stenosis. With aging and increasingly multimorbidity of the western world population, alternative and less invasive procedures were developed. Transcatheter aortic valve implantation (TAVI) was first introduced in 200222 and mean gradient of 41 mm Hg. Left ventricular ejection fraction (LVEF) was 32%, with akinesia of the inferior wall and septum, and moderate mitral regurgitation.A 83‐year‐old man was electively admitted for intervention and management of severe aortic stenosis with New York Heart Association class III heart failure. The preoperative electrocardiogram (ECG) showed sinus rhythm with LBBB wQRS 150 ms)  and a 3830 Select Secure lead (Medtronic®) was used. Operating the pacing lead alone, with unipolar mapping connected to the pacing system analyzer atrial channel (at a gain setting of 0.05 mV/mm and a sweep speed of 50 mm/sec), the intracavitary electrograms showed a slightly prolonged HV interval (62 ms), with a double His potential . Via the left subclavian vein, 3 catheters were introduced . For His pacing, a fixed curve C315 His sheath (Medtronic® Serena biventricular generator (CRT‐P). RV lead was connected to the RV port for ventricular sensing and backup pacing (in case of loss of His lead capture), and His lead was connected to the left ventricular port. The device was programmed to DDD(R) biventricular pacing, with HBP (programed at 6 mV/1 ms) delivered before RV pacing .The leads were connected to a MedtronicPaced QRS duration was 90 ms on the ECG Figure , consistTransthoracic echocardiography, repeated 48 hours after pacing implantation, showed improvement in overall systolic function (LVEF 44%), without evidence of desynchrony and a normal prosthetic valve function.At 6 months follow‐up, the pacing threshold stabilized at 2 V at 1 ms3Transcatheter aortic valve implantation has revolutionized the management of aortic stenosis and become the standard of care for patients with aortic stenosis at prohibitive surgical risk, and the preferred treatment for many intermediate and high‐risk elderly patients.His‐bundle pacing has the potential to offer ventricular resynchronization, since significant reductions in QRS duration have been observed when stimulating the His‐Purkinje system in patients with LBBB.In the present case, the proximal His recording revealed a split His potential, which is highly suggestive of the presence of intrahisian disease. Pacing slightly distally from this site resulted also in correction of the LBBB (with an evident narrowing of the QRS width from 150 ms to 90 ms). In patients with LBBB, conduction system pacing can deliver cardiac resynchronization therapy by correcting BBB (multi‐layer block with bundle recruitment) to synchronize ventricular activation.Recently,Our clinical case supports the potential effectiveness of HBP in obtaining ventricular resynchronization for patients with LBBB and left ventricular dysfunction, particularly in the context of post‐TAVI conduction disturbances.4Conduction abnormalities after TAVI are relatively common and frequently have indication for implantation of a permanent pacemaker. Although it may not be generalized to all post‐TAVI cases as the block induced mechanically by the valve may be more distal regarding the His‐Purkinge system, His pacing may be useful in the treatment of patients with LBBB and AV conduction disturbance after TAVI with the recruitment of the intrinsic conduction tissue and normalization of intraventricular conduction. This pacing modality reduces the electromechanical desynchrony associated with conventional right ventricular pacing, which could be potentially beneficial in the particularly vulnerable group of aortic stenosis patients treated with TAVI.The authors have no conflict of interest to declare.PSC and MMO: designed and directed the project. JP and PSC: collected the data. PSC: wrote the manuscript with support from JP and MMO.Written informed consent was obtained from the patient for the publication of this case report.


Cox regression was performed to evaluate CMR against all-cause mortality. In this study, 116 patients with pulmonary hypertension-HFpEF were identified. Over a mean follow-up period of 3 ± 2 years, 61 patients with pulmonary hypertension-HFpEF died (53%). In univariate regression, 11 variables demonstrated association to mortality: indexed right ventricular (RV) volumes and stroke volume, right ventricular ejection fraction (RVEF), indexed RV mass, septal angle, pulmonary artery systolic/diastolic area and its relative area change. In multivariate regression, only three variables were independently associated with mortality: RVEF , indexed RV mass  and IV septal angle . Our CMR model had 0.76 area under the curve (P < 0.001) to predict mortality. This study confirms that pulmonary hypertension in patients with HFpEF is associated with a poor prognosis and we observe that CMR can risk stratify these patients and predict all-cause mortality. When patients with HFpEF develop pulmonary hypertension, CMR measures that reflect right ventricular afterload and function predict all-cause mortality.This study aimed to determine the prognostic value of cardiovascular magnetic resonance (CMR) in patients with heart failure with preserved ejection fraction and associated pulmonary hypertension (pulmonary hypertension-HFpEF). Patients with pulmonary hypertension-HFpEF were recruited from the ASPIRE registry and underwent right heart catheterisation (RHC) and CMR. On RHC, the inclusion criteria was a mean pulmonary artery pressure (MPAP) ≥ 25 mmHg and pulmonary arterial wedge pressure > 15 mmHg and, on CMR, a left atrial volume > 41 ml/mThe online version contains supplementary material available at 10.1007/s10554-021-02279-z. Heart failure with preserved ejection fraction (HFpEF) now constitutes approximately half of all heart failure (HF) diagnoses . It is eCardiovascular magnetic resonance (CMR) is the imaging reference standard for volumetric assessment and is emerging as one of the key non-invasive imaging methods to diagnose, and temporally monitor patients with pulmonary hypertension , 6 and pCardiac MR provides added value to the clinical assessment in the prognostic evaluation of patients with pulmonary arterial hypertension  and alloCurrently, there are limited outcome data in advanced stages of HFpEF using CMR, especially in patients with pulmonary hypertension-HFpEF. In addition, it remains unknown if CMR can be used in this patient population to risk stratify patients and predict prognosis .The aim of this study was to investigate if non-contrast enhanced cine and flow CMR could risk stratify patients with pulmonary hypertension-HFpEF and inform prognosis.2 on CMR [This study was approved by the National Research Ethics Service 16/YH/0352) in the UK. The study complied with the Declaration of Helsinki. Patients were identified from the ASPIRE registry  and unde/YH/0352 2 on CMR . PatientCMR was performed on a GE HDx 1.5-T system  using an 8-channel cardiac coil.The protocol included four-chamber (4Ch) and short-axis (SA) cine images, acquired using a retrospectively cardiac gated multi-slice steady-state free precession (SSFP) sequence. We acquired a stack of axial images in the short axis (SA) plane, with a slice thickness of 10 mm with no inter-slice gap or 8 mm with a 2 mm inter-slice gap, from the base to the apex of both ventricles. Time-resolved images of the pulmonary artery were performed using a retrospectively cardiac gated SSFP sequence with a single slice of 10 mm taken perpendicular to the long-axis of the pulmonary artery. The SSFP sequence parameters were: TR 2.8 ms, TE 1.0 ms, flip angle 50°, field of view 48 × 48, 256 × 256 matrix and125 kHz bandwidth.CMR images were manually analysed on GE Advantage Workstation ReportCard software, by an experienced radiographer (DC). All segmentation was done manually. Ventricular volumetric assessment was performed as per guidelines  . All continuous variables are presented as mean (standard deviation). Independent T-test was used to compare the clinical and CMR variables in alive/dead patients. For categorical comparisons, the Chi-square test was used. Further details on statistical analysis are in the supplementary online file. A P-value of 0.05 was considered statistically significant.The baseline demographics of the 116 patients with pulmonary hypertension-HFpEF who met the inclusion criteria are shown in Table 2 vs 66.5 ± 19.1 ml/m2, P = 0.005), whereas, there were no significant differences in LV volumes , LV systolic function assessed by LVEF, LV stroke volume index or LV mass (indexed) (Supplementary Table 1).Left atrial volume index was significantly higher in the patients who were dead at the census  and RVEF significantly lower (P = 0.002) in patients with pulmonary hypertension-HFpEF who were dead compared to those alive at the census date Fig. A.Fig. 1PThe PA diastolic area was significantly increased (P = 0.003). PA systolic area was increased (P = 0.016) and PA relative area change reduced (P = 0.027) in patients who were dead compared to those alive at the census data.At the univariate analysis of demographic and CMR variables, 11 were associated with mortality (Supplementary Table 2). In a forward selection, multivariate cox regression model, only three parameters demonstrated independent association to all-cause mortality in this patient population. These included the CMR parameters–RVEF , indexed RV mass  and IV septal angle  , 3-years (39% vs. 76%) and at 5-years (30% vs. 60%) than patients with indexed RV mass <  = 17 g/m2 (P = 0.0002). Patients with an inter-ventricular septal angle > 139° had a worse survival at 1-year (71% vs. 90%), 3-years (31% vs. 74%) and at 5-years (25% vs. 54%) than patients with an inter-ventricular septal angle <  = 139° (P = 0.0001). Receiver operating characteristic analysis are detailed in Table Pulmonary hypertension-HFpEF with RVEF less than or equal to 49% had a worse survival at 1-year (70% vs 96%), 3-years (44% vs 73%) and 5-years 26% vs 64%), than patients with a RVEF > 49%, respectively (P = 0.0001)  analysis. The minimum score was set at 0 which meant all the three variables were not above their threshold. The maximum score was 3 which meant all the three variables were above their threshold. The CMR score model demonstrated a higher area under the curve than the three variables individually at 0.76, 95% CI 0.67 to 0.83, P < 0.001. The overall sensitivity, specificity and accuracy of a pulmonary hypertension-HFpEF CMR score > 2 for predicting all-cause mortality were 72% (95% CI 59.2–82.9), 71% (95% CI 57.1–82.4) and 71.5% (95% CI 62.4–79.5) respectively Below is the link to the electronic supplementary material.


Background: The impact of concomitant impairments of left and right ventricular (LV and RV) strain on the long-term prognosis of acute ST-elevation myocardial infarction (STEMI) is not clear.Methods: We analyzed CMR images and followed up 420 first STEMI patients from the EARLY Assessment of MYOcardial Tissue Characteristics by CMR in STEMI (EARLY-MYO-CMR) registry (NCT03768453). These patients received timely primary percutaneous coronary intervention (PCI) within 12 h and CMR examination within 1 week  after infarction. Global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS) of both ventricles were measured based on CMR cine images. Conventional CMR indexes were also assessed. Primary clinical outcome was composite major adverse cardiac and cerebrovascular events (MACCEs) including cardiovascular death, re-infarction, re-hospitalization for heart failure and stroke. In addition, CMR data from 40 people without apparent heart disease were used as control group.Results: Compared to controls, both LV and RV strains were remarkably reduced in STEMI patients. During follow-up , 80 patients experienced major adverse cardiac and cerebrovascular events (MACCEs) including cardiovascular death, re-infarction, heart failure, and stroke. LV-GCS > −11.20% was an independent predictor of MACCEs (P < 0.001). RV-GRS was the only RV strain index that could effectively predict the risk of MACCEs . Patient with RV-GRS ≤ 38.79% experienced more MACCEs than those with preserved RV-GRS (log rank P < 0.001). Moreover, patients with the concomitant decrease of LV-GCS and RV-GRS were more likely to experience MACCEs than patients with decreased LV-GCS alone (log rank P = 0.010). RV-GRS was incremental to LV-GCS for the predictive power of MACCEs . Finally, tobacco use (P = 0.003), right coronary artery involvement (P = 0.002), and LV-GCS > −11.20% (P = 0.012) was correlated with lower RV-GRS.Conclusions: The concomitant decrease of LV and RV strain is associated with a worse long-term prognosis than impaired LV strain alone. Combination assessment of both LV and RV strain indexes could improve risk stratification of patients with STEMI.Trial Registration:ClinicalTrials.gov, NCT03768453. Registered 7 December 2018 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03768453. The in-hospital mortality rate of patients with acute ST-elevation myocardial infarction (STEMI) has greatly declined . HoweverThe left ventricle (LV) function is a key prognostic factor for patients with STEMI . AlthougThe impairment of right ventricular (RV) function may also help determine the prognosis of patients with STEMI –9. HowevIn this study, we used feature-tracking (FT) technology based on the CMR cine images of patients with STEMI obtained within their first week of hospitalization and followed the prognosis of each patient. We aimed to investigate the prognostic implication of combinative assessment of both LV and RV strain indexes in patients with STEMI.EARLY-MYO-CMR, NCT03768453). The multi-center registry prospectively includes all-comer patients with STEMI who have undergone CMR imaging  sequence was used to produce cine images . A short-tau inversion-recovery spin echo sequence was used to produce T2-weighted black-blood images . Ten minutes after the administration of 0.1 mmol/kg gadopentetate dimeglumine , late gadolinium enhancement (LGE) images were acquired using an inversion recovery segmented SSFP sequence with a proper inversion time .CMR imaging was performed using 3.0-Tesla scanners . All sequences were acquired in breath-hold with a default field of view (FOV) at 350*350 mmImages were analyzed offline by an experienced reader blinded to the patients' clinical data using commercial software . Contours were acquired according to an established protocol in the core lab , 12. TheAngiographic assessments, including the thrombolysis in myocardial infarction (TIMI) myocardial flow grading (TFG) , were peThe clinical end point of the study was the incidence of composite major adverse cardiac and cerebrovascular events (MACCEs). MACCEs were defined as cardiovascular death, non-fatal myocardial re-infarction, hospitalization for heart failure, and stroke after discharge . Clinicat-test. Variables without normal distribution are presented as median and interquartile range (IQR) and compared using the Wilcoxon rank sum test. Categorical variables are presented as number of cases with corresponding percentages and the differences were compared using the Chi-square test or the Fisher's exact test. The correlation between two continuous variables was evaluated using the Spearman's coefficient. The intra- and inter-observer variability of CMR analysis was assessed using intra-class correlation coefficients (ICC) and Bland-Altman analysis. An ICC > 0.74 was considered high consistency.The distribution of data was determined using the Kolmogorov-Smirnov test. Normally distributed continuous variables are presented as mean ± SD and compared using the Student's p ≤ 0.05) variables in the univariate Cox regression model and other clinically significant variables were included in the multivariate analysis. The discriminative power of the predictors of MACCEs were further assessed using receiver operating characteristic analyses with the optimal cutoff points of continuous MACCEs predictors estimated by the Youden Index. All analyses in this study were performed using SPSS version 23.0 . The additional predictive power of the incidence of MACCEs for concomitantly impaired LV-GCS and RV-GRS compared with that of impaired LV-GCS alone was further assessed using the reclassification analyses . The continuous net reclassification improvement (NRI), which indicates improvement of the prediction, was determined. Statistical significance was set at P < 0.05.The factors influencing the right ventricular strain were determined using logistic regressions. Kaplan-Meier curves were used to illustrate event-free rates, and the differences were compared using the log-rank test. The predictors of MACCEs were determined using multivariable Cox regression analysis. Statistically significant , 80 patients (19.0%) experienced MACCEs, including 8 cardiovascular deaths (1.9%), 19 myocardial re-infarctions (4.5%), 46 admissions for heart failure (10.9%), and 7 strokes (1.7%). P < 0.001; LVGRS: 18.66% vs. 33.65%, P < 0.001; LVGCS:−14.20% vs. −20.81%, P < 0.001; RVGLS: −11.49% vs. −22.54%, P = 0.010; RVGRS: 41.84% vs. 54.38%, P < 0.001; RVGCS: −13.09% vs. −18.93%, P = 0.017).Compared to the control group, participants with STEMI had significantly lower LV and RV strains , with a sensitivity of 48.75% and a specificity of 85.00%. Patients with LV-GCS > −11.20% were significantly more likely to experience MACCEs than patients with LV-GCS ≤ −11.20% . The predictive power of LV-GCS for MACCEs at this cutoff was more accurate than that of LVEF . The Kaplan-Meier curves for MACCEs-free survival were significantly different between patients with LV-GCS beyond or below the cutoff (P < 0.001 by log-rank test) (nk test) .P = 0.004), the optimal cut-off point was 38.79%. The MACCEs-free survival rate was significantly different between patients with RV-GRS beyond or below the cutoff (log rank P < 0.001) (P = 0.010). Patients with reduced RV-GRS but preserved LV-GCS also seemed to have a worse prognosis than patients with higher RV-GRS, but was not statistically significant (P = 0.056) (P = 0.006).Among all RV strains, RV-GRS appeared to effectively predict MACCEs in this study  . Forty-e= 0.056) . The addP = 0.003), an occluded RCA , and LV-GCS > −11.20%  was significantly correlated with decreased RV-GRS (The incidence of reduced RV strain (<38.79%) in patients with occlusions in the left anterior descending branch (LAD), left circumflex branch (LCX), and right coronary artery (RCA) were 37.8, 37.5, and 51.5%, respectively. Tobacco use  registry.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.