This study aimed to create an imaging-derived patient-specific computational model of low-flow, low-gradient (LFLG) aortic stenosis (AS) to obtain biomechanics data about the left ventricle. LFLG AS is now a commonly recognized sub-type of aortic stenosis. There remains much controversy over its management, and investigation into ventricular biomechanics may elucidate pathophysiology and better identify patients for valve replacement. ECG-gated cardiac computed tomography images from a patient with LFLG AS were obtained to provide patient-specific geometry for the computational model. Surfaces of the left atrium, left ventricle (LV), and outflow track were segmented. A previously validated multi-scale, multi-physics computational human heart model was adapted to the patient-specific geometry, yielding a model consisting of 91,000 solid elements. This model was coupled to a virtual circulatory system and calibrated to clinically measured parameters from echocardiography and cardiac catheterization data. The simulation replicated key physiologic parameters within 10% of their clinically measured values. Global LV systolic myocardial stress was 7.1 ± 1.8 kPa. Mean stress of the basal, middle, and apical segments were 7.7 ± 1.8 kPa, 9.1 ± 3.8 kPa, and 6.4 ± 0.4 kPa, respectively. This is the first patient-specific computational model of LFLG AS based on clinical imaging. Low myocardial stress correlated with low ejection fraction and eccentric LV remodeling. Further studies are needed to understand how alterations in LV biomechanics correlates with clinical outcomes of AS. Aortic stenosis (AS) is the most common acquired heart valve disease in the developed world . With thThe goal of aortic valve replacement, through TAVR or surgery, is to halt progression of and reverse pathologic left ventricle (LV) remodeling from chronic increased afterload of the stenotic aortic valve. We believe that a contemporary understanding of AS pathophysiology should encompass detailed analysis of ventricular function. Advancements in computational techniques and imaging have enabled creation of high-fidelity models of the human heart and LV . We prevWe describe the first patient-specific computational model of the LV in a patient with LFLG AS. This model is derived from clinical cardiac computed tomography (CT) imaging which was obtained for TAVR planning purposes. While this study reports an initial case, this method should be scalable to permit greater numbers of patient-specific models to be generated. Future studies should correlate biomechanics data to disease severity, progression, and treatment outcomes.2. LFLG AS was confirmed with dobutamine stress echocardiography. Coronary angiogram confirmed that his prior coronary stents were patent. The Society of Thoracic Surgeon’s mortality score was 11% for isolated surgical aortic valve replacement, rendering this patient a high-risk operative candidate, thus he was considered for TAVR.A 68-year-old man with co-morbidities of hypertension, hyperlipidemia, diabetes mellitus, psoriatic arthritis, chronic kidney disease, and coronary artery disease with prior percutaneous coronary intervention developed progressive AS, limiting his functional status. From transthoracic echocardiography, the LV ejection fraction of 25% was measured and eccentric LV geometry was noted. The mean pressure gradient across the aortic valve was 15 mmHg with an estimated aortic valve area of 0.8 cmImages from the diastolic phase of the ECG-gated CT scan were used to provide geometry for the computational model . CT scanSegmentation of the LV, left atrium, and the aortic root was performed with Mimics version 2.1 . Separate segmentation of the innermost surface of the LV chamber at the endocardium, and the outermost LV surface at the epicardium provided the LV wall geometry .Our computational model platform, which has been described previously, provides realistic anatomy of the chambers and valves and accounts for multiple domains of cardiac function, including electrical activation, valve function and structure, myocardial material properties, myocardial microstructure and fiber orientation, and for blood flow . The LV ,,,,,,,,, and Eight material parameters F is the deformation gradient, J is the determinant of the deformation gradient, f0 and s0 are orthogonal vectors in the fiber and sheet direction in the reference configuration. The volumetric response is governed by:D is the multiple of the bulk modulus Terms The active myocardial tissue response is represented as a time-varying elastance model :σaf . Groups 3, arterial resistance 1.35e+ 02 MPa*sec/mm3, pulmonary vascular resistance 8e+ 0 MPa*sec/mm3, mitral valve resistance 2e+ 0 MPa*sec/mm3, arterial compliance (AC) 1.0e+ 07 mm3/MPa, pulmonary compliance (PC) 7.99e+ 06 mm3/MPa.The model was connected to a lumped-parameter virtual circulatory system for cardiac-cycle simulations run in Abaqus® FEA  . AS was The results of LV stress (kPa) and strain along the direction of the myofibers were obtained at end-diastole and peak systole, and reported as mean ± standard deviation. The t-test was used for statistical comparison of continuous variables.Global LV peak systolic myocardial stress and strain were 7.1 ± 1.8 kPa and −0.07 ± 0.12; global LV end diastolic stress and strain were 0.24 ± 0.17 kPa and +0.07 ± 0.04 . FurtherThis study describes the first patient-specific computational model of the LV in a patient with LFLG AS, and the biomechanics results of myocardial stress and strain. This model was based on imaging obtained for TAVR planning purposes, and the use of specialized software enabled a generic LV model to be rapidly adapted to patient-specific geometry and physiology. The ability to create accurate computational models of the LV in AS facilitates the study of “LV-aortic coupling”, whereby aortic valve pathology is linked to LV function for a more complete understanding of the disease .This model represents an advancement in computational investigations in two respects: 1) a patient-specific model of the LV can now be readily obtained from clinical imaging, rather than dedicated research-specific imaging, and 2) specialized software permitted efficient creation of a highly detailed mesh. Previously, weeks of effort were required for a single user to create highly detailed patient-specific ventricular geometry, whereas the CATIA™ software enabled it to be done by one user in approximately one and a half days. With this LV model having a high degree of detail represented by 91,000 elements, validated computational material properties and physiology, there is great potential to use clinical cardiac imaging for future studies of LV biomechanics in AS.p < 0.01. The LFLG model’s eccentric hypertrophy with a dilated ventricle may explain the pronounced difference in stress distribution among the two models.Our group previously published the myocardial stress associated with “classic” severe AS, where a mean transvalvular pressure gradient ≥40 mmHg exists, using a model of idealized LV geometry with normal LV function . SystoliA computational modeling study by Lee et al. on LV geometry after surgical ventricular restoration for systolic heart failure concluded that a more spherical ventricle shape reduced myocardial stress magnitude and produced a more uniform stress distribution . The eccThere is a growing body of literature addressing the complexity of diagnosing severe AS when LFLG or suspected LFLG is encountered. Although a patient may be thought to have LFLG AS, many studies have used stroke volume index to help differentiate true low-flow, low-gradient AS from normal flow, low-gradient AS . This haA study by Shavik et al. applied computational simulation techniques to replicate the physiology of heart failure with preserved ejection fraction (HFpEF), whereby decreased longitudinal strain exists with a normal ejection fraction . ThroughOur results include strain along the direction of myofibers, a microscopic tissue-level organization of the myocardium. The differences between the LV segment strains at diastole and systole  indicatein-vivo  are used to calibrate the model, and close correlation was achieved. A patient’s physiology is expected to exhibit normal variation in daily life  and thus we believe the model can yield useful data as long as the model results replicates key physiologic parameters within an acceptable range of the clinically measured values.In our model, AS was created by increasing the aortic valve resistance parameter in the computational circulatory model, rather than creating a physical representation of calcium on the aortic valve restricting leaflet opening. Since our goal was to study the impact of AS on LV biomechanics, it was not necessary to create the physical representation of aortic stenosis, which permitted greater computational efficiency. This preliminary investigation demonstrates the feasibility of creating a patient-specific computational model from clinical cardiac imaging by modification of an existing LV model platform. There is great potential to generate biomechanics data to help elucidate the pathophysiology of LV dysfunction in AS.We describe the first patient-specific LV model in a case of LFLG aortic stenosis and the LV biomechanics results obtained. Compared to idealized LV geometry and normal ventricular function, reduced LV stress, an initial observation of globally reduced LV stress, was quantified. To translate patient-specific computational modeling to the clinical setting, future studies of larger AS populations should correlate biomechanics results with disease progression, ventricular dysfunction, and outcomes after aortic valve replacement. Data beyond traditional flow-derived metrics and ejection fraction should be incorporated into clinical assessment of AS and determination of who should receive aortic valve replacement. With the widespread adoption of TAVR, CT imaging obtained for pre-TAVR planning should yield abundant clinical imaging that can be used to create patient-specific models.


MRI scout images were used to identify affected and remote lung regions within the patients’ cohort and appropriate regions of interest (ROIs) were drawn accordingly. Both lung native T1 and T2 values were significantly higher in the affected areas of patients with COVID-19 as compared to the controls , whereas no significant differences were detected between the remote lung parenchyma of the COVID-19 patients and the controls (both p > 0.05). When a larger ROI was identified, comprising the whole lung parenchyma within the image irrespective of the affected and remote areas, the COVID-19 patients still retained higher native T1  and T2 values . According to the receiver operator characteristics curves, the T2 value of the affected region retained the higher accuracy for the differentiation of the COVID-19 patients against the controls . These findings, possibly driven by the ability of MRI tissue mapping to detect ongoing inflammation in the lungs of patients with COVID-19, suggest that T1 and T2 mapping of the lung is a feasible approach in this clinical scenario.Tissue characterization by mapping techniques is a recent magnetic resonance imaging (MRI) tool that could aid the tissue characterization of lung parenchyma in coronavirus disease-2019 (COVID-19). The aim of the present study was to compare lung MRI findings, including T1 and T2 mapping, in a group of  Coronavirus disease 2019 (COVID-19) is a respiratory tract infection characterized by a not uncommon development of interstitial pneumonia which can lead to severe respiratory failure and death ,4. We prn = 11 COVID-19 patients in which cardiac MRI imaging was performed during in-hospital stay, which was directed by a guidelines-based clinical indication. An age- and sex-matched group of individuals (n = 11) was randomly selected among non-COVID-19 patients who underwent cardiac magnetic resonance (CMR) at our institution in the past year. Imaging protocol included gradient-echo scout sequences (TRUFI) acquired in the coronal, sagittal and axial planes covering all the chest, cine sequences , and native T1 and T2 mapping, which were all acquired using the same positions . Native T1 mapping was performed by using a modified Look-Locker inversion recovery (MOLLI) sequence with parameters set as follows: TE/TR/flip angle: 1.8/306.20/35°, voxel size 1.6 × 1.6 × 8 mm, base resolution 256, MOLLI scheme 5(3)3 with 8 raw images obtained according to different inversion times. T2 mapping was performed by using a T2-prepared steady-state free precession pulse sequence with the following parameters: three T2W images with different T2 preparation times , repetition time 3 × RR, acquisition time 7 × RR, image matrix 76 × 256, single shot acquisition, flip angle 70°, parallel acquisition (acceleration) GRAPPA.A detailed description of patients’ enrollment protocol at our institution has been previously described . In the p < 0.05 was considered statistically significant.Lung native T1 and T2 mapping assessments were performed by drawing a circular region of interest (ROI) with a diameter of 2 cm in the parenchyma visualized from the cardiac 4 chamber long axis-oriented slice. Vessels and areas of pleural effusion were carefully excluded. As previously reported , the remp = 0.05). Lung tissue mapping analysis revealed significantly higher native T1 and T2 values in the COVID-19 patients as compared with the controls, when the ROI was placed to include the area visually affected by pneumonia ; conversely, non-significant differences were observed between the remote lung areas of the patients and the controls  (p = 0.003) and T2 values  (p < 0.001); regional T1 (remote) 0.198 ; regional T2 (affected) 0.484 ; regional T2 (remote) 0.552 ; global T1 0.963 ; global T2 0.984 .The baseline clinical characteristics of the enrolled patients and MRI findings are summarized in ctively) . When a  = 0.04) . The ROCTo the best of our knowledge, this is the first report describing lung MRI T1 and T2 mapping findings in hospitalized patients with COVID-19 pneumonia and healthy controls. Native T1 and T2 values of the lung parenchyma were higher in the patients than in the controls, either when using a regional or global measurement approach. The T2 value of the affected regions retained the best diagnostic accuracy to differentiate the patients against the controls, whereas a higher reproducibility was obtained when assessing the global lung native T1 and T2 values. Myocardial native T1 was higher in the COVID-19 patients than in the controls.MRI mapping techniques are increasingly used to characterize myocardial changes in a variety of clinical conditions ,8,9, incIn our cohort of patients with COVID-19, T1 and T2 mapping lung MRI identified pneumonia-related abnormalities, likely representing edema and ongoing inflammation of the lungs. Measuring T2 mapping within the affected areas seems to retain the best diagnostic accuracy, though the global assessment of the whole lungs provided higher reproducibility. Myocardial native T1 was higher in the COVID-19 patients than in the controls, indicating the concomitant cardiac involvement.


There is a discrepancy between epicardial vessel patency and microcirculation perfusion in a third of patients treated with percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). Optimization with aspiration thrombectomy (AT) may reduce distal embolization and microvascular obstruction. The effect of AT in the treatment of STEMI is debatable. The purpose of this study was to use cardiac magnetic resonance (CMR) to determine whether AT influences microvascular obstruction (MVO), infarct size and left ventricular (LV) remodelling in STEMI patients. Sixty STEMI patients with a thrombus-occluded coronary artery were randomized in a 2:1 fashion to receive PCI proceeded by AT (AT + PCI group), or PCI only. MVO, myocardial infarct size and LV remodelling were assessed by CMR during the index hospitalization and 6 months thereafter. The majority of patients had a large thrombus burden (TIMI thrombus grade 5 in over 70% of patients). PCI and AT were effective in all cases. There were no periprocedural strokes. CMR showed that the addition of AT to standard PCI was associated with lesser MVO when indexed to the infarct size and larger infarct size reduction. There were less patients with left ventricle remodelling in the AT + PCI vs. the PCI only group. To conclude, in STEMI patients with a high thrombus burden, AT added to PCI is effective in reducing infarct size, MVO and LV remodelling.  The ST-segment elevation myocardial infarction (STEMI) annual incidence rate is estimated at three million cases worldwide ,2. DespiCoronary microvascular obstruction (MVO), which is associated with the no-reflow phenomenon, is partly caused by distal embolization ,8. A recIn recent years, novel advanced imaging techniques of the coronary arteries and myocardial tissue, including highly sophisticated cardiac magnetic resonance (CMR) modalities, became available. This allowed for a precise assessment of the impact of thrombus burden reduction on infarct size, scarring and LV remodelling ,13. AlthTherefore, in the present study we aimed to evaluate whether the use of AT as an adjuvant therapy to standard PCI in STEMI patients is associated with MVO, infarct size and left ventricular (LV) remodelling in STEMI patients using CMR perfusion assessment.We included 60 consecutive patients diagnosed with STEMI, who had a total occlusion of the infarct related artery (TIMI Flow 0–1) with a thrombus visible on the coronary angiogram and who were referred for PCI. The exclusion criteria were as follows: a symptom onset > 12 h prior to admission, left bundle branch block, haemodynamic instability , a prior STEMI in the same location, any contraindication for glycoprotein IIb/IIIa inhibitor (GPI) administration, extreme tortuosity of the IRA, a reference diameter < 2.5 mm proximal to IRA occlusion, and any contraindication for CMR. The study protocol was summarized in Directly after coronary angiography, patients were randomly assigned in a 2:1 ratio to one of two treatment groups: Group I—the AT plus PCI group (AT + PCI group) where thrombus aspiration was performed, followed by routine PCI with stent implantationGroup II—where PCI was performed, without AT (PCI only group).All patients received identical standard premedication treatment periprocedurally and during the follow-up period, in adherence to the European Society of Cardiology Guidelines . All patIn the AT + PCI group, AT was performed using the mechanical Rescue System™  with an active lumen diameter of 0.042 inches. Aspiration was performed from the end of the guiding catheter to the site of the occlusion and distally, with at least two passages or to maximum elimination of the visible thrombus. If an attempt to perform AT across the lesion was unsuccessful, a predilation with a small balloon (≤2.0 mm) was performed and aspiration was attempted again. In all cases, following the opening of the IRA, the procedure was optimized by a stent implantation with a high-pressure technique. Post procedural distal embolization and TIMI Myocardial Perfusion Grade (TMPG) were assessed. Angiographic analysis was performed post hoc using Acom PC  by two independent, experienced operators. The primary endpoints were: the extent of MVO, MI size and the occurrence of LVEDV enlargement  assessed by CMR . DemograBlood levels of creatinine kinase MB isoform (CKMB) were evaluated on admission, 24 and 48 h after reperfusion. The sum of CKMB released was calculated as the area under the release curve  in order to estimate infarct size, as part of an established method ,17.Standard electrocardiograms (25 mm per second recording speed and 1 mV per centimetre voltage) were recorded for all patients on admission, directly post-procedurally, one and two hours after reperfusion. The sum of ST segment elevation in the J point was measured by two independent, experienced cardiologists in accordance with the method previously described .2, TR = 3.0 ms, TE = 1.3 or 1.2 ms, flip angle = 59 or 700). Morphologic images were acquired in short axis views with T2-weighted triple inversion recovery (TIRM)  and T1-weighted turbo spin echo imaging . Ten minutes after intravenous infusion of 0.1 mmol/kg body-weight gadobutrol  LGE imaging was performed in apical LV long axis and short-axis views with T1-weighted, segmented, inversion-recovery pulse sequence .The primary and secondary endpoints were evaluated using CMR . CMR was performed twice: between day 3 and 5 of the index hospitalization (CMRindex) and 6 months post PCI (CMRfollow-up). CMRindex encompassed cine, morphologic and late gadolinium enhancement (LGE) imaging, whereas CMRfollow-up only encompassed cine and LGE imaging. Cine imaging was performed in apical left ventricular long and short-axis views encompassing the entire LV myocardium with balanced steady-state–free precession gradient echo  by an independent reader (TMJ) blinded to clinical and angiographic data. As previously described, endocardial and epicardial LV borders were outlined on short-axis cine images to calculate ejection fraction (LVEF) as well as end-diastolic volume (LVEDV), and myocardial mass (LVmass) which was indexed to body surface area (LVMass index). The cut-off value for the occurrence of adverse LV remodelling six months after STEMI was defined as an enlargement of LVEDV of at least 12% . TIRM imp = 0.05. Statistics were calculated using JASP 0.11.13. Descriptive statistics were used to summarize the data of the cohorts. The distribution of data was evaluated using the Shapiro-Wilk test. Due to the lack of normal distribution, the results were shown as median . Comparative statistics used the non-parametric U Mann–Whitney test for numerical variables and the chi-squared test for categorical variables. An essential level of significance was assumed at n = 40) and the PCI alone Group (n = 20). The median age was 55 [16.5] years in the AT + PCI group and 57 [20.0] years in the PCI only group, p = 1.0. There were no significant differences between the two groups in terms of atherosclerosis risk factors or comorbidities .This is particularly important, as our cohort represents a group of relatively young patients with a median age of 55 (16.5) years in the AT + PCI group and 57 (20.0) years in the PCI only group, with a high prevalence of anterior STEMI, in whom both the quality of life, and life expectancy due to the risk of adverse cardiovascular events should be particularly addressed. Reports indicate that in young STEMI patients, severe thrombus formation is more frequent when compared with older patients, and the left anterior descending artery is the predominant IRA that requires more complex management . In a stIn addition, in the present study most patients presented with a high thrombus burden  . The facStudy limitations. This was a relatively small study, however with regard to group characteristics, ours is a representative of a typical STEMI population. Despite the small sample size, to our knowledge, this is the most complete evaluation of the effect of AT on CMR outcomes in PCI-treated STEMI patients. A follow-up CMR assessment was possible in 45 out of the initial 60 patients. Other authors report similar difficulties, with a 75% effective CMR follow-up ,39. TherWe found that in relatively young STEMI patients presenting with a large thrombus burden, AT adjuvant to primary PCI was associated with a reduction in microvascular obstruction and a decrease in MI size. Aspiration thrombectomy added to PCI significantly reduced the LVEDV increase, leading to an overall lower incidence of LV remodelling in comparison with patients treated with basic PCI. Taken together, our current findings suggest that adjunctive AT may benefit STEMI patients who are at high risk of distal embolization due to a large thrombus burden.


Introduction: The study aimed to evaluate the diagnostic value of global and regional myocardial deformation parameters derived from two-dimensional speckle-tracking echocardiography to detect functionally significant coronary artery stenosis.Methods: Dobutamine stress echocardiography and cardiac magnetic resonance myocardial perfusion imaging (CMR-MPI) were performed on 145 patients with a moderate and high probability of coronary artery disease (CAD) and LVEF≥55%. Significant CAD was defined as>50% stenosis of the left main stem,>70% stenosis in a major coronary vessel, or in the presence of intermediate stenosis (50-69%) validated as hemodynamically significant by CMRMPI. Patients were divided in two groups: non-pathological (48.3%) vs pathological (51.7%), according to CAG and CMR-MPI results. Afterwards, off-line speckle-tracking analysis was performed to analyse myocardial deformation parameters. Results: There were no differences in myocardial deformation parameters at rest between groups, except global longitudinal strain (GLS) and global radial strain (GRS) were significantly lower in the CAD (+) group: -21.3±2.2 vs.-16.3±2.3 (P<0.001) and 39.7±23.2 vs. 24.5±15.8 (P<0.001). GLS and regional longitudinal strain rate (SR) had the highest diagnostic value at high dobutamine dose with AUC of 0.902 and 0.878, respectively. At early recovery, GLS was also found to be the best myocardial deformation parameter with a sensitivity of 78%, specificity 67%, AUC 0.824.Conclusion: Global and regional myocardial deformation parameters are highly sensitive and specific in detecting functionally significant CAD. The combination of deformation parameters and WMA provides an incremental diagnostic value for patients with a moderate and high probability of CAD, especially the combination with regional longitudinal SR. Stress echocardiography (SE) is a well-validated and cost-effective imaging modality in the detection of CAD, and it is widely used for selecting patients for invasive CAG. Although exercise echocardiography is preferred in many cases, dobutamine stress echocardiography (DSE) offers an alternative by minimising factors that decrease image quality. However, knowing the potential limitations only moderate reproducibility has been observed with DSE even by experts.6 A clinical study by Uusitalo et al. clearly illustrated the value of 2D global longitudinal strain (GLS) separately or in combination with DSE, where STE can increase the sensitivity of SE and provide information on the location, extent, and severity of myocardial ischemia in combination with visual wall motion during DSE.7 Small recent studies suggest that regional longitudinal deformation parameters could also have potential in detecting CAD, while the diagnostic value of regional circumferential and radial myocardial deformation parameters to predict functionally significant CAD still are not clear.9 In the present study, we sought to describe both: global and regional longitudinal, circumferential, and radial deformation parameters, which were derived from 2D STE and wall motion score as well as to evaluate the diagnostic value of these parameters for the detection of functionally significant CAD. 2D speckle-tracking echocardiography (STE) derived deformation is a newer approach to assess myocardial deformation and may improve the diagnostic value of SE by permitting quantification of global and regional myocardial function.10 Patients were not included in the study with any of the following criteria: acute coronary syndromes, LVEF < 55% at rest on echocardiography, wall motion abnormalities (WMA) at rest or previous myocardial infarction, valvular heart disease, previous cardiac surgery, implanted pacemaker, non-sinus rhythm, known hypersensitivity to contrast agents, mental diseases, pregnancy or breast-feeding, severe renal impairment (estimated glomerular filtration rate ≤30 ml/min/1.73m2), contraindications to CMR-MPI. Any other structural heart disease that could cause perfusion defects (e.g. hypertrophic cardiomyopathy) was excluded from the study by performing standard echocardiography and CMR-MPI for all patients. We prospectively enrolled 170 patients who were referred to the Department of Cardiology of Lithuanian University of Health Sciences from 2013 through 2016 for investigation of stable chest pain and had moderate or high pre-test probability of obstructive CAD on the types of symptoms, age, and sex. The study protocol included DSE, CMR-MPI and invasive CAG. CMR-MPI and invasive CAG were performed on average 4 ± 1 weeks after DSE. Of the 170 patients, 13 were excluded due to a poor acoustic window, 9 - due to inconclusive DSE results. Late gadolinium enhancement was found for 3 patients who were excluded from the research and 145 patients with a moderate or high probability of CAD were included in the study.11 LV end-systolic volume (LVESV) and LV end-diastolic volume (LVEDV) were measured, and LVEF was calculated using Simpson’s biplane technique. Qualitative assessment of regional wall motion was performed for each patient by dividing the LV into 16 segments. Each segment was then scored individually based on its motion and systolic thickening , and wall motion score index (WMSI) was calculated as the sum of the segment scores divided by the number of segments scored. Images were analysed by at least three experienced echocardiographers blinded to the results of other investigations. The worsening of contractility induced by dobutamine in two or more adjacent segments was considered a positive result. All patients were imaged in the left lateral decubitus position using a commercially available system  with a 1.5 – 4.6 MHz transducer. Standard 2D images and Doppler data were acquired from parasternal long and short axis views and apical  views, which were acquired at rest, at a dobutamine dose of 20 mg/kg/min, at peak stress, and at early recovery 1 min after stress. Echocardiographic views were saved in cine-loop format from four consecutive beats. Standard echocardiographic measurements were performed according to current recommendations.12 Beta-blockers were discontinued 48 hours, nitrates - 12 hours before the study. Intravenous dobutamine was infused through a peripheral infusion line with a mechanical pump, starting with 5 μg/kg/min and increasing to 10, 20, 30, and 40 μg/kg/min at 3-minutes intervals. If no endpoint is reached, atropine (in doses 0.25 mg up to a maximum of 2 mg) was added to the 40µg/kg/min dobutamine infusion. Electrocardiogram (ECG) and arterial blood pressure were monitored continuously. The dobutamine infusion was terminated if 85% of the maximal predicted heart rate was achieved, obvious echocardiographic positivity, severe chest pain or obvious electrocardiographic positivity. The stress test was terminated prematurely in the presence of any non-tolerable symptom or side effect.12 DSE was performed using a standard protocol. Off-line speckle-tracking analysis  was performed using images obtained during DSE. Cardiac cycles associated with atrial or ventricular extrasystolic beats were excluded. To achieve optimal imaging quality for subsequent analyses, the frame rate ranged from 60 to 100 frames per second. End-systole was identified as corresponding to the aortic valve closure measured by pulsed-Doppler. For strain and strain rate (SR) measurements, the endocardial borders were traced automatically with aid of manually marked reference points at the end-systolic frame in the three apical views and parasternal short-axis LV view at the level of the papillary muscles. The quality of tissue tracking was verified by the software’s own quality control function, as well as the visual assessment of the reader. In case of poor-tracking quality, the reference points were manually readjusted until satisfactory tracking was achieved. Patients with two or more segments with poor tracking even after manual correction were excluded from further analysis. After satisfactory tracking was obtained, numerical and graphical displays of myocardial deformation parameters were generated automatically for all six segments from each view.14 Global and regional strain and SR analysis were performed. Strain and SR were measured in each of the 16 LV segments. Average strain values were calculated for the whole LV  and the myocardial regions subtended by major coronary arteries . Stenosis in the left main coronary artery was considered to affect both the left anterior descending and left circumflex coronary artery regions. LV GLS was calculated from loops acquired from the apical 2-, 3-, and 4-chamber views. LV global radial strain (GRS) and LV global circumferential loops are acquired from the LV short-axis view at the level of papillary muscles. End systolic and peak systolic radial and circumferential strain and SR were measured from mid-short-axis view at rest and peak dobutamine dose. End systolic and peak systolic longitudinal strain and SR were measured from apical 4- and 2-chamber and 3-chamber views according to existing guidelines.15 Rest first-pass perfusion images were acquired > 15 min after stress perfusion imaging. The late gadolinium enhancement (LGE) images were obtained 10 min after gadolinium injection in long- and short-axis planes. Cine and LGE images were acquired at the identical long- and short-axis orientation. CMR images were acquired using a 1.5 T MRI scanner  with a dedicated 18-channel phased-array receiver coil in the supine position. Cine images were obtained with a balanced steady-state free precession (bSSFP) sequence in three long-axis views, followed by a contiguous stack of short-axis views covering the entire LV from base to apex. The following imaging parameters were used: repetition time (TR) = 5.1 ms, echo time (TE) = 1.3 ms, flip angle = 80°, in-plane spatial resolution 0.9 × 0.9 mm with a slice thickness of 8 mm and 25 phases per cardiac cycle. First-pass stress perfusion imaging was performed using a saturation-recovery prepared bSSFP sequence  over 50 consecutive heart beats. The images were acquired after 4 min of 140 µg/kg/min adenosine infusion and high-rate injection of 0.1 mmol/kg gadobutrol . In cases of the inadequate hemodynamic response, the adenosine dose was increased up to 210 µg/kg/min.16 LV volumes (LVEDV and LVESV) were quantified using manual planimetry of the endocardial and epicardial surface from a short-axis stack and LVEF and myocardial mass were calculated. Perfusion defects were defined as subendocardial or transmural visually dark myocardial areas when compared with remote myocardium, persisting for at least 10 frames. The stress and rest perfusion scans were reviewed simultaneously, and areas of hypoperfusion were assigned to the ventricular segments, using the standard American Heart Association (AHA) 16-segment model.17 Myocardial tissue was considered infarcted if the signal intensity on LGE images was > 5 standard deviations above that of the remote myocardium. All images were analysed using dedicated software  following a recent consensus document for quantification of LV function and mass using CMR. After DSE and CMR-MPI all patients underwent invasive CAG. Angiography was performed using a standard protocol with a minimum of two projections obtained per vessel distribution by two experienced cardiologists. Angiographic data were analysed by three experienced investigators blinded to the DSE and CMR-MPI results. Significant CAD was defined by invasive CAG as > 50% stenosis of the left main stem, > 70% stenosis in a major coronary vessel, or in the presence of intermediate stenosis (50-69%) validated as hemodynamically significant by CMR-MPI, when perfusion defect was found. The other patients that had no significant coronary artery stenosis were included in the non-pathological group . Statistical analysis was performed using the IBM SPSS 25.0 software package. Qualitative variables were described with their frequency and relative frequency rate (%). Qualitative variables’ homogeneous distribution was evaluated by chi-square (χ2) test . For comparison of quantitative variables, the Mann Whitney U, Student’s T-test, paired Student’s T-test, and non-parametric Kruskal-Wallis test were used. The quantitative trait, which did not satisfy the conditions of normality, was described by the median (min-max). The strain and SR parameters as CAD indicators were evaluated by using ROC curves. A subject was assessed as positive or negative according to whether the parameter value was greater, less, or equal to a given cut-off value. Associated with any cut-off value was the probability of a true positive (sensitivity) and a true negative (specificity). A commonly used index of accuracy is the area under the ROC curve (AUC), with values close to 1.0 indicating high diagnostic accuracy. A p-value less than 0.05 was considered statistically significant. To describe the intra-observer variability, the same investigator re-evaluated regional longitudinal strain and SR on two separate occasions of 20 randomly selected patients at rest, as well as at high dobutamine dose. To evaluate inter-observer variability, two investigators blinded to previously obtained data, performed the same measurements. Intra-observer and inter-observer variability values were calculated as the absolute difference between the corresponding two measurements as a percent of the mean.P = 0.89). At peak stress, 87 vs. 75% of segments. The study population consisted of 145 individuals (68 [46.9%] men) without a history of CAD. Based on Diamond-Forrester risk score, 57.9% of the study group had moderate (15-85%) and 42.1% had high obstructive CAD risk (> 85%). LVEF was normal in all patients . Detailed clinical characteristics are shown in  Invasive CAG was performed on all 145 patients. CAG detected stenosis ≥70% in 75 patients. There were also 9 cases in which CAG confirmed ≥50% stenosis of the left main stem. Other angiographic findings of patients are shown in  All patients were evaluated by conventional cardiac magnetic resonance (CMR) and adenosine stress magnetic resonance. Conventional CMR measurements are shown in  There were 60 positive and 85 negative DSE results. The sensitivity and specificity of inducible WMA for detecting myocardial ischemia were 78% and 83% (AUC 0.767) at peak dose. Regional deformation parameters were compared according to vessel-based analysis. There were no differences in peak systolic, early, and late diastolic longitudinal, circumferential, radial strain and SR parameters at rest between the groups  except G Regional longitudinal and radial strain at high dobutamine dose were significantly lower for patients in the CAD (+) group . GLS and All projections systolic SR parameters at high dobutamine dose were significantly lower for patients in the CAD (+) group . Regional longitudinal and radial early diastolic SR parameters significantly decreased in CAD (+) group patients and were significantly lower. Circumferential early diastolic SR showed no statistically significant change from rest to high dose in both groups and had no significant difference between the groups. Only longitudinal late diastolic SR showed statistically significant change from rest to high dose and was significantly lower in CAD (+) group patients. Circumferential and radial late diastolic SR had no significant changes and did not differ between the groups . All global and regional longitudinal and radial strain parameters at early recovery phase remained lower for CAD (+) group patients . Circumf Regional systolic SR at early recovery phase was lower for CAD (+) group patients . RegionaP = 0.741). The third best parameter was GRS at high dobutamine doses with an AUC of 0.854 with a sensitivity of 84%, specificity of 78%. Radial systolic SR, also, showed the same tendency to have a good diagnostic value and had AUC of 0.835 . Diagnostic accuracy of global and regional systolic circumferential parameters was significantly lower compared to longitudinal and radial but had significant value for ≥ 70% CA stenosis prediction . According to ROC analysis of diastolic deformation parameters, longitudinal and radial early diastolic SR parameters had sufficient predictive value for detecting CAD with longitudinal early diastolic SR having the greatest AUC of 0.778 . Radial early diastolic SR sensitivity was 72%, specificity 65%, AUC 0.735. Circumferential early diastolic SR had no significant predictive value (AUC 0.667). Radial and circumferential late diastolic SR had the same tendency and had no significant diagnostic accuracy for detecting CAD, but longitudinal late diastolic SR showed to be a significant predictor and had a similar diagnostic value as radial early diastolic SR . The greatest diagnostic accuracy for hemodynamically significant stenosis had GLS at high dobutamine doses  . Moreove GLS as the greatest CAD predictor was found analysing images at early recovery phase, but the diagnostic value was lower compared to high dobutamine dose phase evaluation . The second-best diagnostic parameter evaluating the recovery phase was, also regional longitudinal systolic SR . GRS and radial systolic SR showed the same tendency to be good predictors as in high doses phase . The evaluation of regional and global circumferential parameters at early recovery phase revealed that diagnostic value significantly decreased and became not sufficient  for detecting CAD was comparable to WMSI measured during stress.19 Our study demonstrated a similar tendency and GLS and GRS were significantly decreased in the pathologic group even at rest, but regional deformation parameters had no significant difference. Myocardial deformation imaging utilizing STE enables quantification of global and regional myocardial function and evaluation of LV longitudinal, circumferential, and radial motion.20 Compared with our study results, a higher accuracy of GLS was found and this fact further increased the clinical value of this parameter. The other study of G. Dattilo et al. modified the GLS parameter and calculated deltaGLS ([(stress strain – rest strain)/rest strain] x100).21 ROC analysis showed that deltaGLS had high accuracy with AUC 0.916 in distinguishing positive and negative coronary CT angiography groups and predicting CAD, but our study CAD improves the probability of CAD with more sensitive test - CMR-MPI. A systematic review of diagnostic value of longitudinal deformation parameters to predict coronary artery stenosis demonstrated that GLS measurements during dobutamine stress resulted in a far better diagnostic accuracy for CAD than the resting values, and the best results showed evaluation in high dobutamine dose with sensitivity 84% and specificity 88%.7 Our results are in line with several previous studies showing that strain and SR imaging during DSE are useful for the detection of acute and stable CAD.26 Regional longitudinal parameters showed a good potential in detecting CAD, however, the heterogeneity for obtaining regional data remains a challenge.20 Shimoni S et al. study demonstrated the comparison of global and regional longitudinal strain and showed that GLS has a higher accuracy for detecting significant stenosis .27 Since GLS value has been demonstrated in many studies, recent clinical trials have been focused on regional deformation parameters, where functional confirmation of the hemodynamic significance of coronary stenosis is by FFR and/or PET imaging.28 They found the tendency that these strain measurements can predict > 50% and > 75% stenosis, but with a different accuracy. The highest diagnostic value for severe stenosis had the same parameters as in our study – GLS and GRS with AUC of 0.896 and 0.866, respectively. Circumferential parameters had significantly lower diagnostic accuracy compared with longitudinal and radial, especially, predicting > 50% stenosis (GCS 0.723 vs. GLS 0.899 vs. GRS 0.873). The other study showed greater longitudinal and radial value than circumferential – MY. Xie et al. analysis of patients with multivessel CAD.29 This study found a significant decrease only of longitudinal and radial deformation parameters in patients with multivessel CAD, but circumferential parameters had no significant difference. The research of Li L. investigated the relationship between three main projections of LV myocardial mechanics  evaluated by speckle-tracking echocardiography and degree of coronary artery stenosis.7 Isolated WMA diagnostic accuracy was 0.68, in combination with STE parameters in high dose – WMA + strain 0.70, WMA + SR 0.71, WMA + PSI 0.69, at recovery phase – WMA + strain 0.75, WMA + SR 0.78, WMA + PSI 0.79. These findings agree with our study that SR can provide the highest additional diagnostic value in combination with WMA. One of the main multicentre study which analysed the incremental value of 2D speckle-tracking strain imaging to wall motion analysis for detection of CAD, found that the combination longitudinal strain and WMA had the highest sensitivity, specificity, and accuracy .24 The results of combinations with circumferential and radial strain parameters were: sensitivities - 73.9%, 78.3%, specificities - 78.6%, 57.1%, accuracies – 0.757, 0.703, respectively. As the study showed, the longitudinal strain analysis had a higher diagnostic accuracy than circumferential and radial strains. The differences between this and our study looking at radial projection can be determined by a smaller number of patients and using no test of validation of functionally significant coronary artery stenoses in this study. Visual WMA analysis is subjective and considerable expertise is required to achieve high diagnostic accuracy. The quantitative analysis of myocardial deformation by strain and SR imaging in combination with WMA may help to provide an incremental value for CAD detection. The same Finland scientist study demonstrated that STE parameters evaluated in different phases of dobutamine stress  in combination with WMA provided additional value over visual analysis alone.31 Dagdelen et al. demonstrated that both strain and SR correlated with FFR within the left coronary system.32 In another study, haemodynamic significance of intermediate coronary lesions was assessed by Weidemann et al., where SR was the best predictor with a sensitivity and specificity of 89% and 86% respectively.26 The strength of our study is that all patients had functional coronary artery stenosis confirmation using CMR-MPI, while most of the previous studies did not analyse haemodynamic significance of coronary stenosis. The most accurate method for the measurement of haemodynamically significant CAD is FFR during diagnostic CAG, however, it is an expensive and invasive method.33 Indeed, recently published meta-analysis of 3788 patients from 23 studies, the sensitivity of CMR at the patient-level were 90% , specificity 94%  and pre-vessel diagnostic performance sensitivity was 91% .34 Moreover, few studies compared CMR with FFR. The first study enrolled 103 patients with intermediate or high pre-test probability of CAD showed very good accuracy of functionally significant CAD as assessed by FFR.35 Another study by Watkins S. et al. also proved that CMR can show excellent sensitivity, specificity, and positive and negative predictive values compared with FFR.36 Optimization of standardized CMR protocols now places this method as a potential first-line modality of suspected CAD, however, the adoption of this technique has been largely limited to major centres.37 In recent studies, it was revealed that CMR has excellent diagnostic performance in the detection of functionally significant CAD defined according to gold standard FFR. Kamiya K. et al. reported the highest overall sensitivity of CMR compared with PET and WMA diagnosed on DSE. Our study results show that STE-derived GLS helps to assess myocardial ischaemia with very high sensitivity and specificity. Even slight changes and myocardial dysfunction caused by a single diseased vessel could be detected with STE, so it could be also a beneficial tool when there are contraindications to cardiac CMR.34 Thus, we relied on a CMR-MPI for evaluation of the functional severity of coronary stenoses. Secondly, single-centre character and the assessment of strain and SR confined to a single vendor of echocardiographic equipment may also be considered as a limitation of our study. Moreover, contrast imaging during DSE, which could improve the diagnostic value of DSE, was not used in our study. As it was demonstrated by Nagy et al., both tissue velocity and speckle-tracking-based myocardial deformation analysis are feasible during contrast-enhanced DSE, but they failed to demonstrate a clear diagnostic benefit of additional strain analysis over expert wall motion scoring alone.38 Another limitation is that strain and SR can be related to some other cardiac disease than CAD, e.g. arterial hypertension. However, the prevalence of this CAD risk factor did not differ significantly between groups (p = 0.18). Moreover, all patients in our study had normal LVEF and no evidence of other structural heart diseases. Therefore, our results may not apply to patients with cardiac conditions other than CAD. However, our study had some limitations regarding the methodology. Firstly, one of the main limitations of our study is that our protocol did not include FFR as a reference standard for the functional assessment of coronary artery stenosis. According to a recent meta-analysis, CMR-MPI had the highest performance for diagnosis of ischaemia-causing CAD when directly compared with FFR.40 Generally, SR measurement is more sensitive to noise, curves are more complex, and it is quite often difficult to interpret them compared to strain curves. Therefore, a skilled professional is needed to identify SR parameters, and those professionals are not available in every echo lab. Thus, this is a significant limitation in daily clinical practice. Lastly, we excluded 13 patients with the suboptimal echocardiographic visualization assessment of the endocardial border. However, this is in line with recently published data focusing on the reproducibility of this technique in a general DSE population and should also be considered in light of the 8% of DSE studies that are uninterpretable for conventional visual analysis. This is one of the first studies showing that global and regional myocardial deformation parameters are highly sensitive and specific in detecting hemodynamically significant, validated by perfusion defects, coronary artery stenosis in patients with moderate and high probability of CAD. However, global deformation parameters should be selected as a higher diagnostic accuracy having indicators. Despite high myocardial strain and SR accuracy, the combination of deformation parameters and WMA can provide an incremental value for CAD detection, especially the combination with systolic SR. All authors played a key role in the study. This research was funded by a grant (No. MIP-037/2013) from the Research Council of Lithuania. This study was approved by the Kaunas Regional Biomedical Research Ethics Committee (No. BE-2-21). Written informed consent was obtained from all patients. The authors declared no potential conflicts of interest with respect to the research, authorship, and publication of this article.


ROC analysis demonstrated an excellent discriminatory power for nT1 in detecting the iPPM . nT1 and PPM-ls are valid tools in assessing iPPM with the advantage of avoiding contrast media administration.Papillary muscle (PPM) involvement in myocardial infarction (MI) increases the risk of secondary mitral valve regurgitation or PPM rupture and may be diagnosed using late gadolinium enhancement (LGE) imaging. The native T1-mapping (nT1) technique and PPM longitudinal strain (PPM-ls) have been used to identify PPM infarction (iPPM) without the use of the contrast agent. This study aimed to assess the diagnostic performance of nT1 and PPM-ls in the identification of iPPM. Forty-six patients, who performed CMR within 14–30 days after MI, were retrospectively enrolled: sixteen showed signs of iPPM on LGE images. nT1 values were measured within the infarcted area (IA), remote myocardium (RM), blood pool (BP), and anterolateral and posteromedial PPMs and compared using ANOVA. PPM-ls values have been assessed on cineMR images as the percentage of shortening between end-diastolic and end-systolic phases. Higher nT1 values and lower PPM-ls were found in infarcted compared to non-infarcted PPMs (nT1: 1219.3 ± 102.5 ms vs. 1052.2 ± 80.5 ms and 17.6 ± 6.3% vs. 21.6 ± 4.3%;  The left ventricular papillary muscles (PPMs) are intracavitary muscular structures arising from the ventricular wall, modulating the function of the mitral valve (MV) .The PPM involvement during myocardial infarction (MI) represents one of the most frequent causes of ischemic secondary MV regurgitation  and independently increases the mortality rate .PPMs have peculiar vascular anatomy: posteromedial (PM) PPM has a single arterial supply (63% of the population), commonly by the right coronary artery (RCA) posterior descending branch in the case of a right-dominant system, or by the left circumflex artery (LCX) or obtuse marginal branch (OM) in a left-dominant system. Conversely, the blood supply of the anterolateral (AL) PPMs group is generally dual (71% of the population), both from LCX/OM and the left anterior descending artery (LAD) through the first diagonal branch , with hiThe ischemic injury of PPMs causes impairment of its contractile function and a reduction in systolic shortening (PPMs dysfunction) and may be related to MVR, especially when the ventricular function is compromised, resulting in poorer prognosis ,7.Eitel I. et al. demonstrated that the presence of iPPM was associated with larger infarcts, less myocardial salvage, impaired left ventricular function, and more pronounced reperfusion injury, with consequent greater risk of major adverse cardiac events . MoreoveThe detection of iPPM may improve risk stratification and therapeutic decision-making in MI patients.Transthoracic echocardiography (TTE) may evaluate the kinetics and morphology, of PPMs, which is particularly useful in ruling out PPM rupture. However, the angle dependency of the TTE technique and its intrinsic limitation in tissue characterization hamper the accuracy of detecting iPPM .Cardiac magnetic resonance (CMR) has been established as the best non-invasive modality for iPPM assessment because of the high spatial resolution and intrinsic contrast of soft tissues, enhanced by the use of a gadolinium-based contrast agent (GBCA). The identification of myocardial edema in T2 weighted sequences and necrosis in the late gadolinium-enhanced (LGE) images enables characterization and quantification of the myocardial damage.Native T1 mapping (nT1) imaging, based on the relaxometric properties of a normal and pathological myocardium, represents a novel quantitative biomarker that allows for the assessment of the severity and extent of injured myocardium, even without GBCA administration ,11.It is known that the PPM signal follows the modification of the adjacent myocardium in CMR sequences and nT1 mapping images, however, it has not been established yet if the PPM nT1 mapping values change in accordance with the ventricular wall myocardium during MI and may detect iPPM .As a further advantage of CMR imaging, the assessment of PPM dysfunction by cine-MR images may be implemented by the recent introduction of “tissue tracking” based strain analysis.The analysis of papillary longitudinal strain (PPM-ls) improves the evaluation of PPM dysfunction, as already demonstrated in many echocardiographic studies, and it could be helpful when iPPM is suspected ,13,14.To the best of our knowledge, no study has investigated the diagnostic performance of nT1 mapping and strain analysis in the assessment of PPM involvement in acute MI.The purpose of our study was therefore to test the diagnostic capability of nT1 mapping sequences and strain evaluation to detect iPPM in a cohort of ST-elevation myocardial infarction (STEMI) patients.We retrospectively selected 46 patients who underwent CMR examination between 14 to 30 days after STEMI from 2018 to 2021 and had signs of recent MI at both coronary angiography and CMR . The MI-to-CMR time range was set between 14 and 30 days in order to reduce the edema interference in the myocardial nT1 relaxation time, as it is well-known that edema has a bimodal increase pattern up to 7–10 days after MI, with a progressive decrease in the following days/months ,16.Poor CMR image quality (non-diagnostic images for the presence of artifacts or excessive noise) or papillary muscle thickness < 4 mm;Known or evidence of prior myocardial infarction or non-ischemic cardiomyopathies at CMR;Rapid ventricular response-atrial fibrillation (RVR-AF) or tachyarrhythmias;Implantable cardioverter-defibrillator/pacemaker bearers;The exclusion criteria were:Ethical Committee approval and written informed consent from all participants were obtained.T2-weighted Short Tau Inversion Recovery (T2-STIR) sequence acquired on the short axis , on 2-chamber and 4-chamber views ;Modified Look-Locker Inversion Recovery sequence for nT1 mapping, acquired on three short-axis slices at basal, mid-ventricular, and apical views and one four-chamber view before the administration of a single dose of 0.15 mMol/Kg gadoterate dimeglumine ;Cine-Steady State Free Precession sequences for cineMR imaging, acquired on the short axis  and 2-, 3- and 4-chamber views ;Contrast-enhanced Inversion Recovery T1-weighted images acquired from 15 to 20 min after GBCA injection, during breath-hold at end-diastole in the short axis  and then on the 2-, 3- and 4-chamber views  for LGE imaging.All CMRs were performed on a 1.5T scanner  using body and phased array coils. The CMR protocol included:Field inhomogeneity correction, noise reduction, and motion correction were performed by using the algorithms incorporated in the package with standard settings.CMR images were analyzed by two experienced radiologists with six and fifteen years of experience using dedicated software  in consensus.First, the overall diagnostic quality of the CMR exam was evaluated to assess the eligibility of each patient. Second, the image quality of the nT1 maps was assessed using a 5-point Likert scale  with the focus on image noise, edge conspicuity, motion, and co-registration artifacts, field inhomogeneities, and tuning frequency-offsets.Ventricular volumes have been measured using cineMR images. In particular, epi- and endocardial LV borders were traced on the short-axis images in a semiautomatic fashion, and body surface area (BSA) was used to index the parameters.Short- and long-axis T2-STIR and LGE images were used to individuate the infarcted area (IA), area at risk (AAR), non-ischemic remote myocardium (RM), and intraventricular blood pool (BP) as previously described  Figure . Using TThe presence of MVR was detected in echocardiographic exams and during the CMR exam and classified as no-regurgitation, mild, moderate, and severe.All patients were classified into two groups (iPPM and niPPM) based on the presence or absence of iPPM, respectively.Hyperintense area within AM- or PM- PPM on T2-STIR images (short and/or long axis views);Hyperintense area within AM- or PM- PPM on LGE images (short and/or long axis views);Obstructive coronary artery disease at coronary angiography in the culprit vessel .iPPM was defined by the presence of all of the following three criteria:The systolic and diastolic length of the PPMs were assessed on cineMR images acquired on the horizontal and vertical long-axis views, and then the PPM longitudinal strain (PPM-ls) was calculated using the Lagrange strain formula, as follows :PPM-ls= vs. CNR(iPPM/BP) and CNR(IA/RM) vs. CNR(iPPM/RM).The contrast-to-noise ratio (CNR) of the nT1 values between IA and BP/RM and between iPPM and BP/RM was also quantified according to the following formulas:To evaluate the inter-observer variability, the two observers independently measured the nT1 values of the PPMs from 10 STEMI patients with iPPM and 10 STEMI patients without iPPM. One of the two observers measured the nT1 value of the PPMs twice to assess the intra-observer variability. The time delay between two reads for the intra-observer variability was at least 2 weeks.All of the data were analyzed using SPSS . Continuous parameters are presented as mean  ±  standard deviation (SD) and categorical ones are expressed as numbers (%).p values < 0.05.To assess the difference between the groups (iPPM vs. niPPM), one-way analysis of variance (ANOVA) and the Student’s T-test were used for continuous variables. The Chi-square test was used to assess the difference for categorical variables. A univariate analysis was performed for the parameters that showed statically significant values. Variables were considered significant at The Bland–Altman analysis was used to assess the interobserver reproducibility of the method, and then the intraclass correlation coefficient (ICC) was used to evaluate the intra- and inter-observer variability for measuring the nT1 of the papillary muscle.Pearson’s correlation coefficient was calculated to evaluate the relationship between the PPMs’ nT1 and the PPMs’ morpho-dynamic measurements .p-value < 0.05 in the univariable analysis were included in the multivariable linear regression analysis (stepwise method). A p-value < 0.05 was considered statistically significant.Variables with a A receiver operating characteristic (ROC) curve was performed to assess the sensitivity and specificity of the nT1 and PPM-ls values in detecting iPPM.The final population consisted of 46 patients (38 men) with a mean age of 59.5 ± 12.6, which were classified into the iPPM group (n = 16) and niPPM group (n = 30).The patient selection scheme is reported in There was no significant difference in the gender, age, MI-to-CMR interval, body mass index (BMI), presence of systemic arterial hypertension (HTN), diabetes mellitus (DM), smoking, and family history of MI between the two groups.p > 0.693 for all the variables).Most of the patients were male (82.6%), with comparable sex prevalence (88% vs. 80%), age (60 ± 9 vs. 59 ± 14), and onset (17 ± 8 vs. 18 ± 6) between the two groups (The iPPM and niPPM groups did not show significant differences in terms of LV- and right ventricular (RV) ejection fraction (EF), indexed end-diastolic volume (EDV), end-systolic volume (ESV), and stroke volume (SV), as reported in p: 0.093–0.517 for all the parameters).The nT1 values of RM, IA, and BP did not show significant differences between the two groups (p: 0.879). Only eight patients showed mild MVR and one patient from the niPPM group suffered from moderate MVR.Most of the patients (80%) were not affected by MVR, with no significant difference between the iPPM and niPPM groups , good in 18 (39%), and excellent in 25 (54%) patients.p < 0.001), and also when the AL-PPMs and PM-PPMs were separately analyzed (p < 0.001 for both).Infarcted PPMs showed increased nT1 values when compared to the non-infarcted ones (p < 0.001), whereas no significant differences were found between the infarcted PPMs and IA (p = 0.657) and non-infarcted PPM and RM (p: 0.240), as shown in The nT1 values of the infarcted PPMs were also higher than those of RM (p: 0.457–0.622) as summarized in The PPMs’ systolic and diastolic length values were comparable between the iPPM and niPPM groups (p = 0.002), which was also confirmed in the AL-/PM-PPM subgroup analysis (p = 0.009–0.011), as shown in However, infarcted PPMs showed a reduction in PPM-ls when compared to the non-infarcted-PPMs , as shown in All of the CNR values calculated in the T1 maps are reported in Two cases of iPPM involving the AL- and PM-PPMs are reported in p < 0.001), and an accuracy rate of 74%. The PPM-ls had an inferior diagnostic performance with an AUC = 0.701 . The Youden test was performed to individuate the best nT1 and PPM-ls cut-off values, in order to diagnose the iPPM, which resulted in being 1191.5  and 17.8% , respectively.ROC analysis  showed tIn our study, we investigated the performance of the nT1 mapping sequences and strain evaluation to detect iPPM in the STEMI patients.The main findings of our study include (1) the good-to-excellent image quality of nT1 maps, with high CNR between iPPMs and RM or intracavitary BP; and (2) the good performance of nT1 and PPM-ls, assessed as longitudinal percent shortening of PPM, in iPPM identification.Previous reports have demonstrated a high accuracy of nT1 mapping in the diagnosis of MI by using LGE as the reference standard, but there is no evidence of its performance in detecting iPPM as yet .The identification of PPM abnormalities by CMR may be hindered by the inherent limitations of the T2-STIR and LGE sequences, which are prone to motion artifacts and partial volume effects in uncooperative patients and subjects with high or irregular heart rate. Furthermore, the contrast resolution between PPMs and adjacent LV cavity is variably influenced by slow flow phenomena in T2-STIR or high blood signal from persistent gadolinium enhancement in the LGE images .The nT1 mapping technique has been emerging as a valid alternative in the assessment of MI, thanks to its ability to distinguish the intrinsic relaxometric characteristics of the ischemic tissues in comparison with the healthy myocardium, even without the need for GBCA administration. In addition, in the nT1 maps, the motion artifacts were reduced by the application of the motion correction algorithm before curve-fitting and map generation ,20,21.In our study, the image quality of nT1 maps was generally good-to-excellent, and the depiction of PPM from the cavity was clear in almost all patients, rarely hampered by artifacts .Moreover, when the diagnostic quality of the nT1 maps was not optimal, the nT1 relaxometric values of the PPMs were calculated by measuring the signal values of PPM for each inversion time, then generating the T1 signal decay curve.Quantitative analysis, obtained by calculating the CNR values, revealed similar contrast resolution in differentiating IA and infarcted PPMs from RM or intracavitary BP.This could be an advantage over the LGE images, where the increasing use of faster protocol or lower GBCA dose may lead to insufficient wash-out of circulating gadolinium or enhancement of infarcted tissue, resulting in suboptimal contrast between the BP and PPMs and the IA size underestimation ,22,23,24Furthermore, we demonstrated an excellent discriminatory power and accuracy rate of nT1 in detecting iPPM, with good sensitivity and high specificity  for 1191.5 ms as the threshold. On this ground, the measurement of PPM nT1 can be useful when the T2-STIR and LGE images are not clear or affected by artifacts.Another innovative result provided by our study is the efficiency of PPM-ls analysis in the evaluation of post-ischemic PPMs contractile dysfunction.Although no differences in PPM length were found in the comparison between infarcted and non-infarcted PPMs, in both the end-systolic and end-diastolic phases, longitudinal percent shortening measured by PPM-ls was significantly different.This finding suggests that ischemic injury predominantly affects the dynamic properties of PPMs, rather than anatomical ones, as previously demonstrated in echocardiographic studies . PapillaThe use of T1 mapping sequences and strain analysis has improved the quantitative evaluation of tissue and functional features in the assessment of MI patients, introducing new biomarkers, whose clinical values are yet to be established.Native T1 mapping could enable the implementation of faster protocols by replacing conventional T2-STIR and LGE sequences without the use of GBCA administration, which could be particularly useful in uncompliant patients or with contraindications to GBCA.As previously discussed, iPPM may worsen the prognosis for patients with MI because of the risk of acute mechanical consequences such as papillary muscle rupture or chronic PPM dysfunction with the development of post-ischemic MVR .Notably, no significant differences were observed in MVR prevalence between patients with or without iPPM. Although the small sample size of our population limits the generalization of the results, this finding supports the evidence that the pathophysiological link between iPPM and post-ischemic MVR occurrence still needs to be clarified, as various anatomical and functional conditions may be involved . Moreover, it should be noted that our patients were examined during the subacute post-infarction phase, and, therefore, a later onset in the chronic phase of MV regurgitation cannot be excluded.Conversely, in chronic ischemic cardiopathy, the scarring of PPMs and the outward displacement of the PPMs associated with LV wall remodeling may cause the “tethering” of mitral leaflets and result in mitral valve complex deformity and secondary MVR ,30,31.The detection of the ischemic involvement of PPMs and subpapillary regions of the LV wall could help to identify patients who are at risk of developing MVR ,30.Furthermore, the implication of iPPM in the post-ischemic LV remodeling process is still controversial ,32,33. MThe main limitation of our research was the small sample size of the cohort, especially of the iPPM group, who were analyzed in a single-center retrospective study.Additionally, we did not perform a quantitative assessment of the ischemic burden in order to explore the relationship between IA extent and iPPM occurrence. In our cohort, all iPPM patients presented an increased signal of infarcted PPM in both T2-STIR and LGE, therefore, the nT1 signal in the isolated edema of PPMs without necrosis (no enhancement in LGE images) was not investigated. Finally, the lack of clinical or CMR follow-up data did not allow us to assess the clinical relevance of this diagnosis, which would require targeted investigations of a larger population with longer follow-up.iPPM diagnosis is an ancillary CMR feature, which improves the prognostic stratification in subacute MI patients. nT1 mapping and PPM-ls may be considered as valid tools in detecting iPPM with the advantage of avoiding GBCA administration and is a quantitative approach.


We aimed to test the diagnostic performance of a novel, Doppler-based method to evaluate PVR based on Ohm’s law  obtained from peak tricuspid gradient employing a fixed right atrial pressure estimate, PCWPecho was estimated as 10 or 20 mmHg using age-related mitral E/A cut-offs and cardiac output from left ventricular outflow. In the derivation cohort, both PAMPecho and PCWPecho estimates demonstrated excellent agreement with catheterization measurements. PVRecho was highly feasible, demonstrated negligible bias and excellent agreement with PVRRHC  and outperformed the Abbas method to identify PVRRHC > 3WU . In the validation cohort, PVRecho preserved good invasive agreement with negligible bias, displayed strong diagnostic performance (AUC = 0.84) and significant ability to distinguish isolated post-capillary from combined post- and pre-capillary pulmonary hypertension (PH) subgroups (AUC = 0.77).Simultaneous right heart catheterization (RHC) and echocardiography was performed in a derivation cohort of 111 patients in sinus rhythm referred for PH evaluation and PVRecho based on Ohm’s law employing pragmatic estimates of PCWPecho demonstrates excellent agreement with invasive reference standard measurements and strong diagnostic ability to identify elevated PVRRHC. This novel approach may be useful during therapy selection to distinguish PH hemodynamic subgroups.PVR Hemodynamic classification of patients with PH necessitates estimation of pulmonary vascular resistance (PVR), a static index of impedance that reflects pathological remodeling of the distal arterioles and alterations to the pulmonary vascular bed. Accurate quantification of PVR is important for a number of reasons. As a hemodynamic diagnostic indicator, PVR is integral to classifying PH subjects as having isolated post-capillary or combined post- and pre-capillary PH. [4]Reference-standard PVR is assessed using invasive right heart catheterization (RHC). Doppler-based approaches have been proposed 22.1Consecutive patients with unexplained breathlessness referred for clinically-indicated RHC to Norrlands University Hospital between 2010 and 2015 were retrospectively analyzed. Patients with intracardiac or extracardiac shunts and severe valvular disorders were excluded prior to enrollment. Patients with atrial fibrillation or significant arrhythmia and no tricuspid regurgitation (TR) signals on echocardiography were excluded from the final cohort. Ethics committee approval was obtained prior to study enrollment (DNR 07–092M) and all patients provided written informed consent.2.2RHC, PAMPRHC and PADPRHC respectively), and mean pulmonary capillary wedge pressure (PCWPRHC) were measured. Blood samples for estimation of oxygen saturation were drawn from the superior and inferior vena cava, as well as right atrium, and samples from the pulmonary and femoral arteries were used for screening for intra-cardiac shunts. Cardiac output (CORHC) was determined by thermodilution. Pulmonary vascular resistance was calculated using the equation PAMPRHC − PCWPRHC (trans-pulmonary gradient) divided by CORHC.RHC was performed by experienced operators blinded to echocardiographic data. Venous access was obtained by inserting an introducer in a medial cubital vein or in the femoral vein. A retrograde, right-heart catheterization was then performed using a Swan-Ganz pulmonary artery catheter (Edwards Lifesciences). Mean right atrial pressure (RAP), systolic and right ventricular end-diastolic pressures, pulmonary artery systolic, mean and diastolic pressures (PASP2.3echo) was estimated using Continuous-Wave (CW) Doppler from the tricuspid regurgitation (TR) jet considering the most optimal of signals across multiple acoustic windows. Stroke volume (SV) was measured using Pulse-Wave (PW) Doppler at the level of the LV outflow tract, and COecho calculated by multiplying SV with heart rate. Mitral flow interrogation was performed in the 4-chamber view with the PW sample-volume placed between the mitral leaflets tips and measurements taken at end expiration. Early transmitral (E) and late diastolic (A) velocities were obtained after optimal sample alignment and E/A ratio was subsequently computed. Off-line analysis was performed using a commercially available software system . Mean of three consecutive tracings were used to estimate a representative measurement.Doppler Echocardiographic examination was performed by an experienced echocardiographer (PL) with > 15 years’ experience on-table, during RHC using a Vivid 7 system  equipped with an adult 1.5–4.3 MHz phased array transducer. Standard views from the parasternal long and short axis and apical views were used in keeping with current recommendations.echo) was estimated using the hydraulic analogy to the Ohm’s relationship, i.e., PVR = (PAMP − PCWP)/CO employing echocardiographic surrogates for each of the variables employed in conventional equation, i.e transpulmonary gradient and ventricular output. PAMPecho was calculated using the formula PASPecho × 0.61 + 2 mmHg according to Chemla et al. echo was estimated employing the peak trans-tricuspid retrograde pressure drop adding a fixed right atrial pressure (RAP) of 7 mmHg. echo employing current recommendations considering inferior vena cava size and respiratory dynamics.echo was estimated based on combination of interpretation of Mitral E/A ratio and age. PCWPecho was assigned a simplified estimate of 20 mmHg in younger patients (<50 years) if E/A ratio was > 2, and older patients (≥50 years) if E/A was > 1.4. In all other cases PCWPecho was estimated as 10 mmHg. An illustration of PVRecho assessment employing this novel approach has been provided in Fig. 1.Assessment of PVR using echocardiography  analysis was performed to evaluate the diagnostic performance of PVRecho to identify PVRRHC > 3WU. Delong’s method was used to compare area under the curve using the novel PVRecho algorithm and conventional echocardiographic assessment. Sensitivity and specificity were calculated. IBM SPSS statistics version 23.0 was employed for analysis. A p-value < 0.05 was considered statistically significant.Continuous variables were expressed as mean ± SD for parametric variables or median (interquartile range) for non-parametric variables. Categorical variables were expressed as numbers and percentage. PAMP3RHC > 20 mmHg at rest. RHC (>3 WU). When PH patients were classified by etiology, 36 (32%) demonstrated pulmonary arterial hypertension, 40 (36%) had PH secondary to left heart disease, 9 (8%) had PH due to lung disease, 11(10%) demonstrated chronic thromboembolic PH, and 15 (14%) demonstrated PH due to multifactorial mechanisms. When classified by hemodynamic status, 46 PH patients (61%) demonstrated pre-capillary PH (PCWP ≤ 15 mmHg) and 30 (39%) demonstrated post-capillary PH (PCWP > 15 mmHg). Among post-capillary PH patients, 18 (60%) demonstrated isolated post-capillary PH (PCWP > 15 mmHg and PVR ≤ 3WU) and 12 (40%) demonstrated combined post- and pre-capillary PH (PCWP > 15 mmHg and PVR > 3WU).Of 145 patients referred for RHC in the derivation cohort, 32 patients with AF or significant arrythmia and 2 with no TR signals were excluded. In effect, 111  with sinus rhythm were included in the analysis. In the analyzed patient cohort, trivial or mild TR was seen in 88 patients (79%), moderate in 20 (18%) and moderate to severe in 3 (3%). No patients demonstrated free-flowing severe/torrential TR. On catheterization, 35 (32%) did not demonstrate PH and 76 (68%) had PH in keeping with the revised hemodynamic definition of PAMPRHC subgroups. Patients with elevated PVRRHC demonstrated significantly smaller LV volumes and higher EF, larger right atrial (RA) and RV size, and lower RV longitudinal function seen both in lower TAPSE and RV free wall strain .Baseline characteristics of the derivation cohort are presented in 3.1echo using the Chemla’s equation demonstrated strong correlation  and minimal bias  with PAMPRHC. Employing a simplified approach using a fixed, mean RAPecho (7 mmHg), strong correlation  (a) and excellent agreement with PAMPRHC was preserved with a relatively higher spread of data points  (b).TR velocity could be adequately assessed in 96 (86%), and echocardiographic estimates of RAP from inferior vena cava size and collapse in 92 (83%) of patients in the derivation cohort. Applying ASE/EACVI recommended estimates of RAP (12), PAMPor both) a and exc56 mmHg) b.Fig. 2 and outperformed other echocardiographic surrogates i.e., Mitral E , E/e’ , TR velocity  and LA volume index . Further, mitral E/A demonstrated excellent ability to identify elevated PCWPRHC  and E/A cut-off > 2 demonstrated 50% sensitivity and 100% specificity to identify elevated PCWPRHC in the total cohort.Mitral E/A ratio was highly feasible (95%), demonstrated a strong positive correlation with PCWPRHC  (a). Lower sensitivity (46%) and accuracy (82%) but excellent specificity (100%) was observed when E/A > 2 was considered as cut-off in this subgroup. In the younger group (<50 years) mitral E/A cut-off > 2 demonstrated 67% sensitivity, 100% specificity, 100% PPV, 91% NPV and 92% accuracy  (b).Eighty-four patients (76%) were ≥ 50 years and 27 (24%) were < 50 years old in the derivation cohort. In the older (≥50 years) sub-group, mitral E/A > 1.4 demonstrated 69% sensitivity, 96% specificity, 90% PPV, 87% NPV and 88% accuracy to identify elevated PCWP< 0.001) a. Lower  to 1.0) b.Fig. 3(echo as being non-elevated (10 mmHg) or elevated (20 mmHg) considering age in addition to mitral E/A as described in our methods demonstrated excellent diagnostic ability to identify PCWPRHC  in addition to good agreement with PCWPRHC (Kappa coefficient = 0.69). When compared with the current 2016 ASE/EACVI algorithm to determine elevated LV filling pressure, age-dependent mitral E/A demonstrated higher feasibility (95 vs 87%), specificity (97 vs 93%) PPV (91 vs. 32%) and modestly higher accuracy (89 vs 87%) . An illustration displaying age-dependent mitral E/A ratio and corresponding PCWPRHC in addition to PVRecho and corresponding PVRRHC is provided in Simplified estimation of PCWP vs 87%) . An illu3.3echo could be estimated in 88 of 111 patients (79%) employing PAMPecho and PCWPecho in the Ohm’s relationship. When compared with those in whom PVRecho could not be assessed , patients with quantifiable PVRecho demonstrated higher PA pressures and PVR on RHC, and lower TAPSE on echocardiography .PVRecho demonstrated strong association , negligible bias and excellent agreement with PVRRHC on Bland-Altman analysis . (a & 5b) Further, this novel assessment of PVR outperformed conventional echocardiographic assessment using Abbas method (5) to identify elevated invasive PVR > 3WU  (c)PVR2 mmHg). a & 5b Fu curves) cFig. 5  . A relatively higher agreement with RHC was obtained when PVRecho > 4.6WU was employed as cut-off . Further, PVR echo was significantly higher among combined post- and pre-capillary PH patients when compared with isolated post-capillary PH  and demonstrated good diagnostic performance to discriminate these two groups .In the validation cohort, PVR64 mmHg) a and str< 0.001) b. PVRech4echo obtained using this approach was highly feasible, demonstrated strong diagnostic performance and outperformed traditional echocardiographic algorithms to assess PVRRHC. When validated in an independent hemodynamic database of patients referred for PH evaluation, PVRecho preserved strong agreement with RHC measurements, showed excellent ability to identify elevated PVRRHC and strong diagnostic capability to differentiate isolated post-capillary from combined post- and pre-capillary PH. Our findings showcase PVRecho as a promising, non-invasive surrogate of reference-standard PVR that may be useful in diagnosis and regulating PH therapy.We propose a novel echocardiographic approach to assess PVR employing variables routinely obtained in daily clinical practice using the hydraulic analogy to Ohm’s law. Simplified Doppler-based estimates of PCWP and PAMP employed in this equation demonstrated negligible bias and excellent agreement with corresponding invasive measurements. PVR4.1RHC can demonstrate E/A ratio between 1 and 2. However, for values over 2, a sensitivity of 43% and specificity of 99% for identifying elevated PCWPRHC has been reported. RHC. Recently, a model combining TR velocity. E/e’, LV EF, RV fractional area change, IVC diameter and LA volume demonstrated a sensitivity of 92%, specificity of 93% and area under the curve of 0.97 to estimate elevated PCWPRHC. RHC) offers a simple, pragmatic measure with strong diagnostic performance.While the mitral E/A ratio is highly feasible and integral to the assessment of diastolic dysfunction, it demonstrates well-recognized limitations that prevent its use as an independent surrogate of elevated LV filling pressures as per current recommendations 4.2echo was assessed using the validated relationship proposed by Aduen et al. trans-tricuspid gradient.RHC were compared. In this context, a fixed RAP estimate simplifies assessment of PAMPecho using the Chemla approach [20]In this study, PAMPecho as employed in this study requires assessment of PAMPecho, PCWPecho and COecho, and each variable introduces a margin of error. However, we have chosen a pragmatic, simplified approach to assess highly reproducible variables routinely assessed in echocardiography labs worldwide. The variables chosen demonstrate higher feasibility and our approach demonstrates lower complexity when compared with more recently proposed models. One can argue that the assessment of PVR4.3echo outperformed the conventional Doppler-based algorithm postulated by Abbas and colleagues. Our novel approach to assess PVRBeyond PVR, the Ohm’s law relationship considering surrogates of pressure and flow has also been utilized to evaluate systemic vascular resistance in the setting of heart failure 4.4Accurate, non-invasive estimation of PVR employing commonly available echocardiographic variables taking age into consideration may improve patient screening and triaging for invasive catheterization in addition to regulating therapy during follow-up. In addition, this approach may be useful to distinguish PH hemodynamic subgroups where PVR evaluation determines therapeutic management.4.5Although micromanometer-tipped catheters offer high-fidelity pressure recordings and are considered the invasive standard, we employed standard fluid-filled catheters that are routinely utilized in clinical practice. Analysis of echocardiographic images in the validation and derivation sites were performed by two experienced operators employing standard international recommendations, thereby minimizing inter-evaluator variability.4.6echo estimated employing the hydraulic analogy to Ohm’s Law is highly feasible, demonstrates excellent agreement with invasive measurements and identifies elevated PVRecho with high accuracy. This novel, pragmatic approach to non-invasive PVR assessment may be of value in patient screening, diagnosis and PH therapy regulation.PVRThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.


Heart transplant (HTx) still represents the most effective therapy for end-stage heart failure, with a median survival time of 10 years. The transplanted heart shows peculiar physiology due to the profound alterations induced by the operation, which inevitably influences several echocardiographic parameters assessed during these patients’ follow-ups. With these premises, the diastolic function is one of the main aspects to take into consideration. The left atrium (LA) plays a key role in this matter, and that same chamber is significantly impaired with the transplant, with different degrees of altered function based on the surgical technique. Therefore, the traditional echocardiographic evaluation of diastolic function applied to the general population might not properly reflect the physiology of the graft. This review attempts to provide current evidence on diastolic function in HTx starting from defining its different physiology and how the standard echocardiographic parameters might be affected to its prognostic role. Furthermore, based on the experience of our center and the available evidence, we proposed an algorithm that might help clinicians distinguish from actual diastolic dysfunction from a normal diastolic pattern in HTx population. The prevalence of people being affected by heart failure worldwide is incessantly increasing and is now over 60 million . ConsensHowever, survival is still impaired by two groups of transplant-related complications: those dependent on immunosuppressive therapy  and those graft-specific, which include cardiac allograft vasculopathy (CAV) and acute and chronic graft rejection. In a growing donor organ shortage era, avoidance of graft failure as long as possible is of paramount importance.In addition to invasive methods, such as coronary angiography, endomyocardial biopsy, and right heart catheterization, non-invasive methods have been widely used to track changes in post-transplant cardiac function, such as echocardiography, cardiac computed tomography particularly for CAV detection, and recently, cardiac magnetic resonance , 4. It iThe aim of this review is to attempt to provide current evidence on diastolic function in HTx starting from defining its different physiology and how the standard echocardiographic parameters might be affected to its prognostic role.From a histological standpoint, diastolic dysfunction is related to a substantial subversion of the extracellular matrix due to the presence of edema or fibrosis. Such tissue alterations determine the stiffening of myocardial walls and therefore alter lusitropic properties. In various pathological conditions, they occur before the overt manifestations of the disease, leaving space for pre-clinical detection. This could be true also for early identification of graft-specific complications since edema could be the result of acute graft rejection, while fibrosis may be the manifestation of both chronic graft rejection or CAV. However, recent evidence suggests that diastolic function might also be linked to microvascular density . ConsideGraft physiology is considerably different from normal, as a consequence of various factors such as denervation, altered anatomy, and hemodynamic status of the recipient. First, the electrical impulse originates from the donor atrium and, at least in the first 6–12 months after transplant, it is not under any control of the recipient’s nervous system. Because of the reduced variability of heart rate, cardiac output is critically pre-load dependent in HTx. Second, because of the mismatch between the recipient and donor heart dimensions, the cardiac allograft is usually subject to enhanced mobility into the recipient cavity, enlarged by the dilated explanted heart, and clockwise rotated. Finally, atrial contribution to ventricular filling is reduced because of altered anatomy and function consequent to surgical anastomosis. Usually, HTx patients are characterized by restrictive physiology during the first period, probably because of inflammatory edema related to ischemic reperfusion injury, allograft ischemic time, surgery, and/or immune-mediated acute response. During follow-up, the diastolic pattern tends to improve after the first few weeks progressing to a non-restrictive filling pattern during the first year , 9. NoneThe atrial function is variably altered in HTx patients according to the employed surgical technique. With the “biatrial technique,” in which the posterior cuffs of the recipient atria are left in place and attached to the donor atria, the atria result enlarged with an altered geometry, known as “snowman” configuration. In addition, impaired electrical impulse initiation (due to sinus node injury) or conduction could result in brady- or tachyarrhythmias, including atrial fibrillation . To overEchocardiography represents the first-line imaging modality to assess diastolic function and it is the cornerstone exam in the follow-up of HTx patients. However, the evaluation of diastolic function in HTx is challenging since the most widely employed diastolic parameters are sensible to heart motion as well as acoustic angle. Therefore, it is unlikely that the usual cut-off values can be appropriately applied to HTx patients . For theAccording to the latest recommendations , at leasSoon after cardiac transplantation, Doppler echocardiographic indexes of LV diastolic function are suggestive of elevated filling pressures. Particularly, iso-volumetric relaxation time (IVRT) is shortened and the transmitral inflow pattern shows an increase in E wave velocity and a shortening of deceleration time (DT) . The opeAs the diastolic function improves with time, a progression to a non-restrictive pattern is seen. IVRT and DT prolong and transmitral early filling velocities decrease . HoweverIn particular, the proposed algorithm, shown in In HTx, the anastomoses at the level of the pulmonary vein ostia interfere with pulmonary vein flow, except from the biatrial technique . In addip < 0.001), and left atrial volume/BSA (mL/m2), 53 ± 23 vs. 39 ± 13 (p < 0.001). In patients operated on with the bicaval technique, atrial volume correlates only with allograft age instead   . In addi< 0.001) . Also, P< 0.001) . An asso< 0.001) . Further< 0.001) . Rodrigu< 0.001) . A possip < 0.001 and mean LV-GCS −22.9 ± 6.3%; P = NS) possibly due to surgical procedure and progressive remodeling including myocardial fibrosis and/or previous rejections (Due to the aforementioned limitations of the traditional indices of diastolic function for the estimation of LV filling pressures in HTx, the performance of myocardial deformation analysis using STE to predict elevated pulmonary capillary wedge pressure in HTx has been studied. Strain and strain rate parameters such as GLS and GCS have stronger diagnostic performance than traditional parameters of diastolic dysfunction, such as E/e’ . Ingvarsjections , 31. LV-jections . Regardijections , there ijections .Graft failure due to acute cellular rejection is a common complication of HTx and the main cause of mortality in the first years after surgery , whereasDiastolic dysfunction carries a significant prognostic value also in chronic graft rejection, which is mainly determined by CAV and, in some patients, triggered by recurring immune responses against the graft resulting in replacement fibrosis and progressive deterioration of myocardial function, especially in patients with alloreactive antibodies. Histologically, CAV is a diffuse vasculopathy secondary to a fibroproliferative process initially resulting in concentric narrowing of both the large epicardial coronary arteries, the coronary veins, and the microcirculation, and later on, in focal luminal stenoses detectable with coronary angiography . DiastolIn conclusion, no single diastolic parameter reliably predicts graft-specific complications , and a cThe assessment of LV diastolic function is considered an integral part of the clinical evaluation of HTx patients. It carries a relevant prognostic value in the follow-up, helping in the early detection of possible complications such as rejections. However, its assessment requires several considerations due to the profound alterations that the transplanted heart undergoes, especially LA which plays a key role in defining diastolic function.CS, CF, FL, and MB participated in the writing the manuscript. GM and ML provided images and tables as well as a revision of the manuscript, whereas SV, FD’A, MF, and MC critically revised the manuscript. All authors contributed to the article and approved the submitted version.