This study aims to investigate the correlation between myocardial area at risk at coronary computed tomography angiography (CCTA) and the ischemic burden derived from myocardial computed tomography perfusion (CTP) by using the 17-segment model.Forty-two patients with chest pain complaints who underwent a combined CCTA and CTP protocol were identified. Patients with reversible ischemia at CTP and at least one stenosis of ≥ 50% at CCTA were selected. Myocardial area at risk was calculated using a Voronoi-based segmentation algorithm at CCTA and was defined as the sum of all territories related to a ≥ 50% stenosis as a percentage of the total left ventricular (LV) mass. The latter was calculated using LV contours which were automatically drawn using a machine learning algorithm. Subsequently, the ischemic burden was defined as the number of segments demonstrating relative hypoperfusion as a percentage of the total amount of segments (=17). Finally, correlations were tested between the myocardial area at risk and the ischemic burden using Pearson’s correlation coefficient.A total of 77 coronary lesions were assessed. Average myocardial area at risk and ischemic burden for all lesions was 59% and 23%, respectively. Correlations for ≥ 50% and ≥ 70% stenosis based myocardial area at risk compared to ischemic burden were moderate  and good , respectively.The relation between myocardial area at risk as calculated by using a Voronoi-based algorithm at CCTA and ischemic burden as assessed by CTP is dependent on stenosis severity. This algorithm can be used to partition the myocardium according to which blood vessel is closest Artificial intelligence (AI) is rapidly evolving in the work field of cardiovascular imaging and can greatly lessen the time needed for image processing, Machine learning which is a subclass of AI allows for the creation of a model based on historical data. As such, machine learning has been widely used for automatic left ventricle (LV) segmentation greatly speeding up the process of LV contour placement The aim of this study was to assess whether the subtended myocardial mass as calculated by using the Voronoi-based segmentation method correlated to myocardial ischemia at CTP. As such, CCTA may not only be used to assess the degree of a coronary stenosis, but also for the quantification of the subtended myocardial mass which may predict the ischemic burden without the need for a stress test.22.1248 patients referred for a combined CCTA and CTP protocol due to chest pain complaints were identified. Patients with normal CTP images or fixed perfusion defects (N═178), absence of at least one ≥ 50% coronary stenosis (N = 11), inferior CTP scan quality (N = 16) and prior coronary revascularization (N = 1) were excluded 2.2Using a 320-row volumetric scanner  CCTA and static adenosine stress CTP were acquired on the same day. Patients were advised not to consume caffeine products 24 h before examination. One hour prior to CCTA blood pressure and heart rate were monitored. Patients with a heart rate exceeding 60 beats per minutes (bpm) were given metoprolol, 25 mg up to 150 mg orally, unless contraindications were present. Additionally, metoprolol could be injected intravenously if the heart rate remained above 60 bpm.Sublingual administration of nitroglycerin (0.4 mg) was done prior to CCTA. Scanner settings for CCTA were as follows: A detector collimation of 320 × 0.5 mm, a 275 ms gantry rotation time and temporal resolution of 137 ms for the Aquilion ONE Genesis Edition and a detector collimation of 320 × 0.5 mm, 350 ms gantry rotation time and temporal resolution of 175 ms for the Aquilion ONE. Tube current was 140–580 mA and a peak tube voltage 100–135 kV. The antecubital vein was used for administration of 50–90 mL of contrast agent  followed by a 1:1 mixture of 20 mL contrast and saline and finally 25 mL of saline. Tube current, peak tube voltage and the amount of administered contrast agent varied due to variations in patient size CTP was only performed if there was suspicion of a significant stenosis (≥ 50%) at CCTA. To achieve adequate myocardial contrast wash-out the minimum scan-interval was 20 min between CCTA and CTP. ECG and blood pressure were continuously monitored following continuous adenosine infusion (0.14 mg/kg/min) after which a contrast agent was administered. CTP images were acquired when a threshold of 300 HU was reached in the descending aorta scanning 80–99% of the RR interval. Tube settings, injection protocol and contrast agent were all similar to the CCTA acquisition.2.3Images were transferred to a workstation and analyzed using dedicated post-processing software . All CCTA and CTP images were analysed by trained cardiologists with at least 10 years of experience. In accordance with SCCT guidelines, stenosis severity per segment was semi quantitatively assessed using visual analysis as: 50–69% (moderate), 70–99% (severe), and 100% (occluded) CTP images were analysed by reconstructing cardiac phases for every 2% of the scanned interval. Subsequently, analysis was performed on the phase with the best scan quality using short-axis reformatted images and a slice thickness of 4 mm using a narrow window width and level setting (W300/L150) and utilizing the standard 17 segment myocardial model for scoring 2.4Before executing the Voronoi-based segmentation algorithm the complete coronary artery tree was automatically extracted from the CCTA A and theTo assess the feasibility of the machine learning model as compared to manual measurements one observer  randomly selected a sample of 10 cases in which manual reformatting of the short axis and manual drawing of the left ventricular epicardial and endocardial contours was performed. Correlations were subsequently tested between manual and automatic measurements concerning the left ventricular mass which is derived from the epicardial and endocardial contours. Statistical analysis of these correlations was done using Pearson’s correlation coefficient using SPSS software .2.5In order to calculate the subtended mass a Voronoi-based segmentation algorithm was used on the CCTA by using in-house developed MASS software . By using this algorithm it is possible to find the nearest location of the extracted coronary artery tree for every voxel within the left ventricular myocardium Finally, the subtended mass was calculated for both ≥ 50% and ≥ 70% stenosis as a percentage of the total LV mass and defined as the myocardial area at risk using the following formula:2.6Correlations between the ischemic burden and myocardial area at risk as well as correlations between manual and machine learning based LV contours were calculated using Pearson’s correlation coefficient. All analysis were performed using SPSS software .3CCTA and CTP images from forty-two patients  were used for the current analysis. Patient characteristics are listed in Comparison of the LV mass as calculated from manually drawn contours versus contours drawn with the machine learning model demonstrated a very good correlation .4This study assessed the relationship between myocardial area at risk at CCTA and ischemic burden as assessed at CTP. Our results demonstrate that calculating subtended mass using a Voronoi-based segmentation algorithm in combination with a machine learning algorithm for semi-automatically drawing LV epi- and endocardial contours at CCTA is feasible and its correlation to the ischemic burden as measured using a standard 17-segment model at CTP increases with increasing stenosis severity. Consequently, coronary CTA can be used not only to assess the degree of a coronary stenosis, but also for quantification of the subtended myocardial mass which may predict the ischemic burden without the need for a stress test. It should however be noted that the use of integrated diagnostics of CCTA and CTP is still better than CCTA alone as the first allows for both assessment of coronary stenosis as well as the presence of (reversible) ischemia. This is of great importance as not every coronary stenosis is hemodynamically significant Multiple studies have demonstrated that adding CTP to regular CCTA improves the detection of hemodynamically significant coronary lesions Aside from the degree of coronary stenosis there have been several studies assessing the relationship between the anatomical location of a coronary stenosis and the presence of myocardial ischemia. For instance, in a study by Tanabe et al. the combined diagnostic performance of coronary artery stenosis-subtended myocardial volume and myocardial blood flow (MBF) on CTP for detecting obstructive coronary artery disease was assessed. It was found that the AUC of the combined use of the subtended CTP myocardial blood flow and subtended mass was significantly higher than that of myocardial blood flow alone in the detection of hemodynamically significant stenoses  Ide et al. demonstrated the feasibility and validity of Voronoi-based tissue segmentation. It was found that CCTA based subtended myocardial mass calculated using a Voronoi-based segmentation algorithm closely corresponded to actual subtended mass measured on ex-vivo-sine hearts ; r = 0.96, p = 0.009 for the circumflex artery (CX); r = 0.96, p = 0.009 for the right coronary artery (RCA)) Semi-automatic segmentation of the LV using a machine learning model for defining epi- and endocardial contours has been validated extensively. Several studies have reported high comparability to a manual segmentation of the LV versus a machine learning approach Kurata et al. also assessed the relationship between calculated subtended mass at CCTA using a Voronoi-based segmentation algorithm and ischemic burden as assessed by single photon emission computed tomography (SPECT). A moderate correlation was found between the calculated subtended mass and ischemic burden  which is only slightly lower compared to our results  Interestingly, in our study lesions with a diameter stenosis of 70% or more demonstrated a better correlation between the myocardial area at risk and ischemic burden compared to lesions with a diameter stenosis of 50% (r = 0.708 and r = 0.564 respectively). A similar observation was found by Fukuyama et al. 4.1This study has several limitations which are inherent to its retrospective design. Firstly, the amount of analyzed patients is small which may have influenced the strength of the statistical analysis. Hence, future studies with a larger number of patients will be required to clarify the significance of these findings in clinical practice. Selection bias may have been introduced as we only selected patients with reversible ischemia as diagnosed on CTP. Secondly, the subtended mass was calculated using the anatomical location of the relevant coronary lesion. This was independent of whether the lesion was hemodynamically significant or not. In case of multivessel disease the correlation between subtended mass and ischemic burden may have been biased as we solely selected the most proximal lesions for calculating the subtended mass. Of course, the most proximal lesions also encompass the largest subtended mass. Also, there was no validation of the ischemic burden to the corresponding anatomical territory that corresponds to the relevant coronary artery lesion used for calculating the myocardial area at risk 5Quantification of the myocardial area at risk calculated by using a Voronoi-based algorithm in combination with a machine learning based algorithm for LV segmentation at CCTA significantly correlates with the ischemic burden as assessed by the standard 17-segment model at CTP. This correlation improves with increasing stenosis degree. This relationship may be beneficial in risk assessment of patients with CAD and may aid in clinical-decision making.All data were retrospectively analyzed. The local ethics committee of the Leiden University Medical Center approved this retrospective analysis of clinical data and the need for informed consent was waived.This research did not receive any specific grants from funding agencies in the public, commercial, or not-for-profit sectors.Finn van Driest: Conceptualization, Validation, Formal analysis, Writing – original draft, Writing – review & editing, Visualization. Coen Bijns: Writing – original draft. Rob van der Geest: Methodology, Software, Writing – review & editing. Alexander Broersen: Software, Writing – review & editing. Jouke Dijkstra: Software, Writing – review & editing. Wouter Jukema: Writing – review & editing, Supervision. Arthur Scholte: Writing – review & editing, Supervision.All authors have nothing to disclose.


Arrhythmogenic cardiomyopathy is an inherited disease in which the normal myocardium is replaced by fibroadipose infiltrates. It is increasingly being recognized as a separate entity to arrhythmogenic right ventricular cardiomyopathy though is rarely diagnosed. We report a 47-year-old female who presented to her local emergency department with a history of presyncope while driving. Electrocardiograph revealed inferolateral ST changes and right bundle branch block. A high burden of premature ventricular contractions and non-sustained ventricular tachycardia was seen on telemetry. Echocardiography showed reduced left ventricular systolic function and cardiac magnetic resonance imaging demonstrated extensive fibrosis involving the left ventricle and the septum of the right ventricle. An inherited cardiac disease genetic panel, including desmosomal gene mutations, was non-contributary. Extensive workup for other potential causes of cardiac fibrosis and reduced left ventricle function including cardiac positron emission tomography (PET) was negative. Based on the presentation and these findings, a diagnosis of biventricular arrhythmogenic cardiomyopathy was made. The patient’s condition was complicated by third-degree heart block two weeks after initiation of pharmacological treatment that included amiodarone. An implantable cardiac defibrillator was implanted. She was referred to a tertiary centre specializing in inherited cardiac conditions for familial screening. Arrhythmogenic cardiomyopathy (AC) is a rare inherited disease that affects either right, left or both ventricles -4. It isA 47-year-old female presented to the emergency department with multiple episodes of sudden onset dizziness and presyncope. The first episode occurred one week prior to her presentation while she was driving. She was able to stop her car safely and her dizziness resolved after one minute. She had further episodes of presyncope with worsening intensity and increasing duration leading to her presentation to our emergency department. She denied palpitations, shortness of breath, chest pain, or syncope. Physical examination was unremarkable. Her medical history was unremarkable and she was not on any other medications. She was an active smoker with a 10-pack-year history with minimal alcohol intake. A thorough family history did not reveal any episodes of sudden cardiac death or heart disease.The initial electrocardiograph (ECG) revealed multiple ventricular ectopics, right bundle branch block (RBBB), and ST changes inferolaterally with T-wave inversion inferiorly Figure . CompletCardiac magnetic radiography (MRI) cine imaging revealed global LV hypokinesia along with moderately reduced right ventricular function. Disproportionate hypokinesis in the entire septum and LV inferior wall was noted. Post-contrast cardiac MRI demonstrated extensive fibrosis from the base of the left ventricle to the right ventricular septum. It also noted prominent epicardial fibrosis throughout the inferior wall of the LV Figure . These fThe patient was commenced on ramipril, dapagliflozin, eplerenone and amiodarone. After a discussion of the risks and benefits, an implanted cardioverter defibrillator (ICD) was arranged as an outpatient. Two weeks post-discharge, the patient represented with further dizziness and nausea. ECG and telemetry revealed intermittent complete heart block with a QTc of 525 ms. Although she was hemodynamically stable, a decision to insert a dual-chamber intracardiac defibrillator as inpatient was done successfully. She was discharged one-day post-procedure. She is being closely followed in the cardiology clinic and is awaiting an appointment in the national center for inherited cardiac conditions for familial screening.The 2019 Heart Rhythm Society expert consensus statement on arrhythmogenic cardiomyopathy defines ACM as an arrhythmogenic disorder of the myocardium not secondary to ischemic, hypertensive or valvular heart disease . This inIn our patient’s case, the majority of her disease was in her LV, so arrhythmogenic left ventricular cardiomyopathy (ALVC) was initially thought to be the diagnosis. ALVC is increasingly being recognized as a primary disease distinct from arrhythmogenic right ventricular cardiomyopathy (ARVC) ,3,4. An While endomyocardial biopsy remains the gold standard for the definitive diagnosis it has a high false-negative rate and advances in cardiac imaging have allowed for non-invasive diagnosis ,5.While ALVC and ARVC share a similar disease pathology, mode of inheritance and treatment options, ALVC has some unique characteristic features . These fAlthough arrhythmogenic cardiomyopathy is considered an inherited condition, pathogenic mutations are not found in around 50% of patients . FurtherSen-Chowdhry et al. clinical diagnostic criteria encompass the following: inferolateral T-wave changes in ECG, arrhythmia sustained or non-sustained VT, imaging findings of LV systolic dysfunction or aneurysm, and late gadolinium enhancement of the LV on cardiac MRI or fibro-adipose infiltrates on endomyocardial biopsy . While oThe management of arrhythmogenic cardiomyopathy involves managing patient's potential heart failure and life-threatening arrhythmia. Therapeutic strategies include restriction from high endurance activity, ß-blockers, antiarrhythmic and heart failure management, ICD, catheter ablation and, rarely, heart transplant . In our Though reported, the development of bradyarrhythmia is rare in the context of ACM . In thisWe report a case of a 47-year-old lady who presented with multiple episodes of presyncope. Between the ECG, telemetry and imaging findings along with consultation with various diagnostic guidelines, she was diagnosed with biventricular arrhythmogenic cardiomyopathy. Genetic ACM remains a challenging diagnosis as it lacks standardized diagnostic criteria and in the absence of a pathogenic gene requires extensive investigation into other possible causes of ACM. This differentiation between the various forms of ACM is clinically relevant for risk stratification and familial evaluation.


Recent echocardiography studies in inherited long QT syndrome (LQTS) have shown left ventricular (LV) myocardial relaxation disturbances to follow markedly prolonged and dispersed mechanical contraction.We used speckle-tracking echocardiography to assess disturbances in LV myocardial relaxation sequence during exercise and their relationship to symptoms.Forty seven LQTS patients  and 35 controls underwent exercise echocardiogram using Bruce protocol. ECG and echo parameters were recorded at rest, peak exercise (p.e.) and recovery.SR (tESR) at all three LV segments; basal (p < 0.0001), mid- cavity (p = 0.03) and apical (p = 0.03) whereas at rest such difference was noted only at base (p = 0.0007). Patients showed reversed apico-basal relaxation sequence (ΔtESRbase–apex) with early relaxation onset occurring later at base than at apex, both at rest  and at p.e. , particularly in symptomatic patients . ΔtESRbase–apex correlated with longer QTc interval, lower ESR and attenuated LV stroke volume.Between patients and controls there were no differences in age, gender, HR or LVEF. At p.e, patients had longer time to LV longitudinal ELQTS patients show reversed longitudinal relaxation sequence, which worsens with exercise, particularly in those with previous cardiac events. Novel cardiovascular imaging techniques have recently offered new insights into the behavior of the left ventricular (LV) myocardium in inherited long QT syndrome (LQTS). This is no longer regarded as a single electrical phenomenon caused by mutations in genes encoding for cardiac ion channels . MyocardThe resting mechanical contraction disturbances, in LQTS patients, have been shown, in a recent speckle-tracking echocardiography study, to deteriorate further with exercise and to result in myocardial relaxation disturbances in the form of delayed onset of relaxation, shortened LV filling time with its implication on inadequate LV stroke volume (SV) response . Brado eThe aim of this study was to assess disturbances in LV apico-basal myocardial relaxation sequence during exercise and their relationship to symptoms in LQTS mutation carriers.p = 0.2) and gender . None of the participants had electrocardiographic (ECG) or echocardiographic changes suggestive of underlying ischemic heart disease. There was also no evidence for bundle branch block (BBB) on the recorded 12 lead ECGs of the participants. No patient had evidence for other cardiac or valve disease. All patients underwent exercise echocardiographic examination with the following set target: exhaustion, symptoms, arrhythmia or significant drop in systolic blood pressure (> 20 mmHg).We enrolled 47 patients with genetically confirmed LQTS (36 LQTS1 and 11 LQTS2), who were under regular follow-up at Umea University Hospital . They weThe LQTS patients were classified into symptomatic or asymptomatic based on previously documented cardiac events such as cardiac arrest, syncope or ventricular arrhythmias.The exercise test was performed using a supine bicycle, General Electric- GE ergometer . Patients and controls exercised in a semi-supine position  and in stages of incremental 10 Watt increase of workload, every 2 min. Echocardiographic recordings, ECG and blood pressure (BP) were made at three stages: (i) at rest (just before exercise), (ii) at peak exercise (p.e.), achieving 85% of the maximum predicted heart rate (HR) for age, and (iii) at 4 min into recovery.c = QT/√RR). We calculated QTc percentage changes  from baseline to p.e. and recovery.Throughout the exercise test, a 12-lead ECG was continuously recorded, at 25 mm/s with a conventional electrocardiograph, with built-in measurements software. Manual measurements of RR, QT and QRS were performed at the end of each phase. Only resting measurements were available digitally from the electrocardiograph, exercise measurements were made manually throughout all stages. The QT interval was measured from the onset of the QRS complex to the end of the T-wave at the point of the T wave descending limb intersection with the isoelectric line. QT values were corrected for HR, using the Bazett formula  equipped with an adult 1.5–4.3 MHz phased-array transducer. Digital loops of three cardiac cycles were acquired at the end of each exercise phase from the standard apical four-, two-chamber views and parasternal long-axis views. All recordings were made with a superimposed ECG (Lead II).The echocardiogram analysis was performed blindly and off-line on a dedicated work station . LV ejection fraction was estimated using the Simpson’s biplane method and stroke volume (SV) as the product of the LV outflow tract velocity time integral (VTI) and the cross-sectional area. LV Doppler filling velocities (E and A waves) were recorded from the apical four chamber view with the sample volume placed at the orifice of the mitral valve. The recommendations of the European and American society of Echocardiography were used to assess LV diastolic function and LV filling pressures .SR) was determined by the average value of the 16 LV segments’ longitudinal peak positive early diastolic SR.LV longitudinal early diastolic strain (S) and strain rate (SR) assessment by speckle-tracking echocardiography (STE) were performed at basal, mid, and apical levels (16 LV segments) from the parasternal long axis, apical four- and two-chamber views, at a frame rate of 55–80 frame/s. After selection of the optimal left heart image, the end-diastolic LV endocardial border was manually traced while the epicardial contour was automatically drawn by the software . The regSR), a measure of contraction duration and delay in relaxation, defined as the time interval from the QRS onset to the peak positive early diastolic SR . (2) The longitudinal apico-basal myocardial relaxation sequence (ΔtESR base–apex) was defined as the time difference between basal tESR and apical tESR  delayed LV longitudinal early diastolic SR  Theo-apical .SR, ΔtESR base–apex and SV parameters, there was good inter-observer  and intra-observer agreement  at all three exercise phases.In order to assess the inter-observer variability of the speckle-tracking parameters’ measurements, two independent reviewers analyzed the raw images for 20 randomly selected participants. Similarly, the intra-observer variability was assessed based on the analysis of raw data in two different loops. For the QTc, tEP-value < 0.05 was accepted as a significant difference. Continuous variables are expressed as mean ± standard deviation (SD) and categorical variables as absolute number and percentage (%). We used the Chi-square test to assess if distributions of categorical variables were different from one another. For group comparisons, the Student’s t-test was used for variables with normal distribution and the Mann-Whitney U-test for non-normally distributed variables. Pearson’s test was used to assess correlations. Multiple regression was performed to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the outcome “previous cardiac events.” The sensitivity and specificity of ΔtESRbase–apex for identifying previous cardiac events in LQTS patients were investigated using the Receiver Operating Characteristic (ROC) analysis.We used Statistical Package for the Social Sciences (SPSS) for Windows . A two-tailed The study protocol followed the ethical guidelines of the 1975 Declaration of Helsinki and has been approved by the Regional Ethical Review Board ; Dnr 2011-339-31M. All participants gave informed consent.Based on the documented history of previous cardiac events , 20 (43%) LQTS patients were classified as symptomatic; three had implantable cardioverter-defibrillator (ICD) inserted. Fourteen (70%) of the symptomatic (previous cardiac events) and 11 (41%) of the asymptomatic LQTS patients were on regular B-blocker therapy. The fourteen treated symptomatic patients experienced cardiac events prior to the initiation of B-blocker therapy whereas none of them were symptomatic while on B-blocker therapy.p = 0.3), in HR  or in the systolic BP . Two symptomatic patients developed ventricular bigeminy, close to reaching 85% of maximum predicted HR, with exercise. The rest of the participants remained asymptomatic and did not develop any rhythm disturbances.LQTS patients and controls had no significant differences, at rest, p.e. and recovery, in the maximum achieved workload .LQTS patients had longer QTc than controls at all the three exercise phases . The QTcp = 0.3). At rest and at recovery, SV was similar between the two groups (p < 0.0001).Between LQTS patients and controls, there were no significant difference in resting LV EF . Also, E/e’ and E wave deceleration time (EDT) parameters, indirect reflectors of LV filling pressure, were higher in the LQTS patients at all three exercise phases . This was further examined at the LV basal, mid-cavity and apical segments, separately. At rest, patients had more prolonged tESR at the basal and mid LV cavity regions  but not at the apex (p = 0.6) in patients  in relation to the apex (longer tESR), at rest and during exercise, resulting in positive values for Δt ESRbase–apex , lower ESR  and attenuated LV stroke volume .The magnitude of the apico-basal relaxation dispersion  correlatSR than asymptomatic patients, at all three exercise phases  and ΔtESR base–apex at recovery  proved to be independent predictors of previous cardiac events. ROC analysis showed ΔtESR base–apex at peak exercise to be the best identifier  of patients with previous cardiac events followed by ΔtESR base–apex at recovery .On multiple regression analysis which included the parameters of ΔtEp = 0.8), peak exercise  or recovery . However, at peak exercise, untreated patients had more pronounced apico-basal relaxation dispersion and reversed sequence (Δt ESRbase–apex) than treated patients  despite no noted differences at rest . In a similar way estimated LV SV was lower at peak exercise in untreated than in treated patients  whereas no differences were noted at rest .Between treated with B-blockers and untreated patients, there were no significant differences in QTc at rest  or Δt ESRbase–apex . However, at peak exercise, LQT1 patients had longer QTc , greater Δt ESRbase–apex  and more attenuated SV response  than LQT2 patients. At recovery, although there were no significant differences in QTc , LQT2 patients presented greater Δt ESRbase–apex  and more attenuated SV response .At rest, there were no differences between the LQT1 and the LQT2 patients in QTc . This finding provides additional evidence for the presence of electromechanical (EM) coupling disturbances in LQTS (SRbase–apex) correlated with decreased early diastolic longitudinal function (ESR) and with attenuated LV stroke volume response to exercise.Our LQTS patients showed clear evidence for delayed longitudinal myocardial relaxation as a result of prolonged myocardial contraction. This delay appears more pronounced at the LV basal segments compared to the apex. As a result, there was not only an increased apico-basal dispersion in the onset of LV longitudinal relaxation but also a reversed longitudinal relaxation sequence; the onset of basal segment relaxation occurred later than the apex in LQTS patients as opposed to the controls. The magnitude of this apico-basal relaxation dispersion, as reflected by the Δt E in LQTS , irrespe in LQTS . However2 + overload as a result of prolonged action potential in these patients induces early and late potentials which trigger mechanical post-systolic contractions and thus tachyarrhythmias . Finally, cardiac events were identified based on the previously documented history, as the LQTS patients were asymptomatic during exercise, except the two patients in whom the exercise test was terminated prematurely due to arrhythmia.Although LQTS was initially considered to be the result of sole electrical abnormalities, the use of speckle-tracking echocardiography has shown evidence for associated mechanical contraction and relaxation disturbances. Additionally, our results showed reversed longitudinal relaxation sequence with early relaxation phase starting later at LV base compared to the apex. These disturbances worsened at peak exercise, especially in patients with previous adverse cardiac events, and were related to longer QTc, impaired LV diastolic function and attenuated SV response to exercise.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the study protocol followed the ethical guidelines of the 1975 Declaration of Helsinki and has been approved by the Regional Ethical Review Board ; Dnr 2011-339-31M. All participants gave informed consent. The patients/participants provided their written informed consent to participate in this study.DC designed the protocol of the study, submitted to the ethical committee for approval, collected, analyzed, and interpreted the data, drafted the manuscript, and approved the submitted manuscript. GK contributed to the collection, analysis, and interpretation of the data and approved the submitted manuscript. AR and MH contributed in the conception and design of the study, involved in the interpretation of the data, revised critically the manuscript and approved the submitted manuscript. All authors have seen and agreed with the contents of the manuscript and there is no financial interest to report.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


A 9-year-old intact female Maltese dog was admitted for further evaluation of previously diagnosed patent ductus arteriosus (PDA). The dog showed severe coughing and exercise intolerance. On physical examination, a grade VI/VI continuous heart murmur was auscultated. Thoracic radiography demonstrated cardiomegaly, pulmonary overcirculation, and moderate bronchointerstitial pattern. Echocardiography revealed severe dilation of the left ventricle and atrium, decreased left ventricular contractility, and left-to-right PDA. On electrocardiography (ECG), R amplitude was increased. Computed tomographic angiography revealed type IIA PDA. The serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration was >10,000 pmol/L. Transarterial occlusion was performed and the Amplatz® Canine Duct Occluder was successfully deployed. On echocardiography 48 h after the procedure, aortic regurgitation (AR) and residual ductal flow were noted. Long-term follow-up on clinical signs, physical examination, radiography, echocardiography, ECG, and serum NT-proBNP were evaluated until 30 months after correction of PDA. The clinical indices of physical examination, thoracic radiography, echocardiography, ECG, and serum NT-proBNP concentration were improved, although the postocclusion AR and residual ductal flow persisted. The dog followed up without clinical signs for 41 months following the correction. To our knowledge, this is the first case report to demonstrate quite a long time of follow-up (41 months) in an older dog with transarterial occlusion of PDA with postocclusion AR and residual flow. Curr in dogs , 4. The  in dogs . However in dogs –8.® Duct Occluder has been reported in some patients  after percutaneous PDA occlusion using coil or Amplatzpatients , 10. Idepatients .However, postocclusion AR has been rarely reported in dogs after percutaneous closure of PDA, without detailed description and long-term follow-up results , 12. TheA 9-year-old intact female 2.41-kg Maltese dog was admitted for evaluation of previously diagnosed PDA. The dog showed severe coughing and exercise intolerance despite prior treatment with pimobendan , ramipril , furosemide , sildenafil , and codeine .On physical examination, continuous heart murmur (grade VI/VI) was auscultated at the left heart base area. The dog showed intermittent panting after coughing, and resting respiratory rate was 24 breaths/min in the absence of coughing. Body condition score was 2/5, heart rate was 166 beats/min, and blood pressure was within normal range . Complete blood count and serum chemistry revealed mild normocytic normochromic anemia, mild hypoalbuminemia, mildly increased blood urea nitrogen, and aspartate aminotransferase (AST), mild hypocalcemia, hypertriglyceridemia, increased lactate dehydrogenase (LDH), and mild hyperkalemia .Thoracic radiography demonstrated severe enlargement of all four cardiac chambers, a vertebral heart score (VHS) of 13.4, leftward bulge of descending aorta , increased pulmonary circulation, tracheal deviation to the dorsal and right side, and moderate bronchointerstitial pattern on perihilar and caudal lung lobes .Transthoracic echocardiography (TTE)  revealed severe dilation of left ventricle (LV) and left atrium (LA) [ratio of left atrial to aortic root diameter (LA/Ao) = 2.21] and decreased LV contractility [fractional shortening (FS) = 15.7%]. Mild mitral valve thickening and mitral regurgitation (MR) (peak velocity = 3.93 m/s) were observed in color and continuous wave Doppler. PA diameter was significantly enlarged (1.40 cm) compared with the aortic root (Ao) diameter of 1.04 cm. A turbulent flow coming from PDA toward main PA (left-to-right shunt) was observed (peak velocity = 5.49 m/s), with minimal ductal diameter (MDD) of 5.15 mm . Peak aovia surgical cut-down, and 4F vascular long introducer  and 4-mm ACDO  were used because of small size of the dog's femoral artery. The device was successfully deployed, and the continuous murmur disappeared, although grade III systolic murmur remained. The dog recovered from anesthesia without any event and was discharged the following day.The interventional procedure was performed as previously reported . AngiogrThe dog was reexamined 48 h after the procedure. The dog owner reported that the clinical signs including coughing and exercise intolerance were improved. On thoracic radiography, decreased cardiomegaly (VHS = 12.3) and improved pulmonary overcirculation were observed . The TTEAfter 30 months from the ACDO deployment, the dog was presented for recheck. The dog had no clinical signs and returned to normal. On physical examination, a grade II to-and-fro murmur was auscultated at the point of maximum intensity of left heart base. The body weight was increased to 2.7 kg (BCS 3/5), heart rate was 114 beats/min, resting respiratory rate was 24 breaths/min, and blood pressure was within normal range . Complete blood count and serum chemistry revealed mild normocytic hypochromic anemia, mild hyperproteinemia, hypoalbuminemia, hyperglobulinemia, mildly increased AST, moderately increased creatine kinase and LDH, and mild hyperkalemia .Thoracic radiography revealed significant decrease in cardiac size (VHS = 11), pulmonary overcirculation, and interstitial lung pattern compared with the preprocedural radiographs and similarly maintained aneurysmal bulge .On the TTE, LV internal dimensions, LV volume indices, LA dimension, and PA diameter were further decreased, and LV contractility was markedly increased compared with the preprocedural and post−48-h TTE results . The Ao Generally, in dogs, PDA has poor prognosis with a high mortality rate within 1 year if untreated, but long-term survival is possible if corrected at an early age . In caseIn humans, AR is reported to be one of the possible complications following PDA occlusion , 19, 20.® Duct Occluder deployment was more likely to develop in human patients with hemodynamically significant left-to-right PDA shunts, and the MDD indexed to body weight was significantly larger in patients with newly developed AR compared with patients with no AR  was used because of the small size of the dog's femoral artery, which is thought to have contributed to the occurrence of persistent residual ductal flow. In addition, the older age of the dog in this report also may have affected the development of residual flow. In human patients with PDA , age-relIn this case, reduction of FS was observed 48 h after the procedure, whereas significant improvement of FS was confirmed after 30 months. This reduction of systolic function after PDA occlusion was previously reported in dogs and is known to be a result of increased afterload and decreased LV preload . This alAs the PDA correction was not made until late age, the dog in this case showed severe deterioration of cardiac function and remodeling. In addition, because of the concurrence of AR, residual ductal flow, and MR, volume overload may have persisted even after the PDA occlusion. This persistence of volume overload and consequent cardiac damage could be confirmed by increased serum NT-proBNP concentration 30 months after the procedure, despite marked improvement compared with preprocedure. Nevertheless, the dog in this case did not show any clinical signs, and most of the clinical indices including physical examination, radiography, echocardiography, and ECG could be fairly maintained with only pimobendan administration for a long period of 30 months. This outcome represents relatively benign nature of postocclusion AR, which should be distinguished from AR caused by infective endocarditis that may also occur as a postocclusion complication .To the authors' knowledge, this is the first case report describing the long-term follow-up outcome of an older dog with persistent AR and residual ductal flow after ACDO procedure. In older PDA dogs with large and hemodynamically relevant shunts, it should be considered that postocclusion AR may occur after ACDO procedure. Identifying postocclusion AR in PDA dogs would be helpful in prognosis evaluation and patient monitoring, especially when combined with other conditions such as residual ductal flow or MR. Despite several postocclusion complications, ACDO procedure could improve the quality of life and extend the survival time in an elderly PDA dog.The original contributions presented in the study are included in the article/Ethical review and approval was not required for the animal study because this case describes clinical management of an individual animal. Written informed consent was obtained from the owners for the participation of their animals in this study.W-BR, J-HK, and C-HJ contributed to case management. W-BR, H-MP, D-WS, and M-HK contributed to case analysis. W-BR, H-SK, and G-WL contributed to data curation. W-BR contributed to manuscript preparation. W-BR, H-MP, and M-HK contributed to manuscript editing. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Background: Dobutamine stress echocardiography (DSE) has limited application in systemic sclerosis (SSc). We examined DSE usefulness in revealing pulmonary arterial hypertension (PAH) in selected SSc patients whose resting echocardiography for pulmonary hypertension (PH) was non-diagnostic. Methods: Forty SSc patients underwent right heart catheterization (RHC) and, simultaneously, low-dose DSE . Inclusion criteria were: preserved left and right ventricular (RV) function (tricuspid annulus plane systolic excursion [TAPSE] ≥ 16 mm and tissue Doppler imaging-derived systolic velocity of tricuspid annulus [RVS’] > 10 cm/s), normal pulmonary function tests, and baseline maximal tricuspid regurgitation (TR) velocity of 2.7–3.2 m/s. Results: Of 36 patients who completed DSE, resting RHC diagnosed PAH in 12 patients (33.3%). At 20 μg/kg/min, patients with PAH had higher TR velocity, higher pulmonary arterial pressure measured by RHC, and lower RV inotropic response compared with patients without PAH. A cut-off value of maximal TR velocity >3.1 m/s had a sensitivity of 80%, a specificity of 84.2%, and an accuracy of 82.4% for the detection of PAH. Conclusions: Low-dose DSE has a satisfactory diagnostic accuracy for the early detection of PAH in highly selected SSc patients whose baseline echocardiographic measurements for PH lie in the gray zone. Pulmonary arterial hypertension (PAH) is a common complication of systemic sclerosis (SSc) ,2 associExercise stress echocardiography has been applied in the past for the identification of PH in SSc patients , but theRecently, a lower cut-off value, i.e., mean PAP > 20 mmHg measured by RHC along with pulmonary vascular resistance (PVR) ≥ 3 Wood Units and pulmonary arterial wedge pressure (PAWP) ≤ 15 mmHg, for the definition of PAH was proposed  and has We prospectively studied 40 patients with SSc referred to the PH Clinic of Attikon University Hospital for PAH screening. All patients underwent a detailed clinical and laboratory work-up, as described below.1) ≥ 55% of predicted normal and total lung capacity (TLC) ≥ 60% of predicted normal  and RV function (tricuspid annulus plane systolic excursion [TAPSE] ≥ 16 mm and tissue Doppler imaging (TDI)-derived systolic velocity of tricuspid annulus [RVS’] > 10 cm/s), (3) no previous ischemic or valvular heart disease or echocardiographic findings of diastolic dysfunction suggestive of elevated LV filling pressures, (4) sinus rhythm, and (5) forced expiratory volume in 1 s  in line with the latest guidelines of the American Society of Echocardiography and the European Association of Cardiovascular Imaging . AssessmAll patients underwent RHC the day of DSE. RHC was performed 20–30 min prior to DSE in the catheterization laboratory by a single operator (AA) using an echo-guided right internal jugular vein access. Local anesthesia was performed by s.c. lidocaine, and a triple lumen Edwards Swan–Ganz catheter of 7 F was inserted. The following measurements were performed: RAP, PAP , PAWP, and cardiac output (CO) by thermodilution. PVR and cardiac index (CI) were subsequently calculated. For diagnosing PAH, we applied the 2019 proposed criteria , i.e., mBefore the initiation of dobutamine infusion, a resting echocardiographic study was performed in the catheterization laboratory with the patient lying supine. Afterwards, the infusion of dobutamine was started with parallel echocardiographic imaging and continuous hemodynamic recording. Echocardiographic imaging was focused on the 4-chamber view to visualize the tricuspid and mitral valves. Dobutamine was given as a continuous infusion at incremental doses of 5, 10, 15, and a maximum of 20 μg/kg/min. Each infusion stage lasted for 3 min, and during the last 30 s of each stage, both echocardiographic and hemodynamic measurements were performed. Echocardiographic assessment included measurements of maximal TR velocity, transmitral E and A velocities, RVS’, and TAPSE. Hemodynamic assessment comprised measurements of systolic, diastolic, and mean PAP as well of PAWP and CO. All echocardiographic measurements were obtained by a single operator (LSR) blinded to the RHC results. For comparisons of baseline echocardiographic values with RHC measurements, echocardiographic values obtained by resting echocardiography prior to the RHC were used.A 6-min walk test (6MWT) was conducted on a straight pre-marked corridor under the supervision of an expert nurse. Total walking distance and percutaneous oxygen saturation were measured at the end of the test. The appearance of relevant symptoms  was also noted.1 and TLC.All patients had chest X-ray, high-resolution computed tomography (HRCT) of lungs, and pulmonary function tests (PFTs), i.e., FEVFasting blood was drawn the day of catheterization for N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hsCRP), and routine hematological and biochemical measurements.Continuous variables are displayed as means ± standard deviation (SD), while non-normally distributed variables are presented as medians and interquartile ranges. The Student’s t test was applied for independent samples to compare means for normally distributed variables, and the Mann–Whitney test was used for non-normally distributed variables. Categorical data are presented as proportions, and associations between them were tested by the chi-square test.Receiver Operating Characteristic (ROC) analysis was used to identify the optimal cut-off value (best combination of sensitivity and specificity) that distinguished patients with PAH. Sensitivity, specificity, disease prevalence, positive and negative predictive value, and accuracy were calculated and expressed as percentages. Confidence intervals (CIs) for sensitivity, specificity, and accuracy were calculated as “exact” Clopper–Pearson CIs, and the CIs for the likelihood ratios were calculated with the “Log method” . CIs forp value < 0.05 was used to indicate statistical significance. The Statistical Package for the Social Sciences (SPSS) release 26.0  was used.A During the period 2018–2020, 40 of 150 patients with SSc referred to the PH clinic fulfilled the inclusion criteria and agreed to participate. Of those, two had a poor-quality TR Doppler signal during dobutamine infusion, and two developed a hypotensive response (symptomatic drop of systolic blood pressure ≥ 20 mmHg from baseline or previous level of infusion) leading to premature termination of DSE . This lep < 0.001) (< 0.001) .p = 0.001). A cut-off value of maximal TR velocity at 20 μg/kg/min > 3.1 m/s had a sensitivity of 80%, a specificity of 84.2%, and an accuracy of 82.4% for the detection of PAH established by RHC (A ROC curve analysis of maximal TR velocity discriminated the patients as those with RHC-validated PAH and those without it (AUC = 0.852 with 95%CI: 0.705–1.000, d by RHC .Ιn the present study, we demonstrated that DSE has a satisfactory diagnostic accuracy for the early detection of PAH in selected patients with SSc, i.e., asymptomatic or mildly symptomatic patients with equivocal resting echocardiographic study for PH and low probability of having PH due to left heart or lung disease. In particular, we found that maximal TR velocity during low-dose DSE > 3.1 m/s had a diagnostic accuracy of 82.4%, with a specificity of ~84% and a moderate sensitivity of 80% for the identification of PAH confirmed by RHC.To our knowledge, this is the first study exploring the usefulness of DSE in SSc for the detection of PAH. Another novel element of our study is the use of the recently proposed cut-off value of mean PAP > 20 mmHg for the diagnosis of PAH .There are few data on the role of DSE in PAH or SSc patients, mainly focused on the assessment of RV inotropic reserve. Ghio et al.  showed iThere are several previous attempts using various strategies or algorithms for early PAH diagnosis in SSc ,8,23. InThe idea to assess pulmonary circulation under dynamic stress has been around for many years. In particular, exercise echocardiography has been used for more than 15 years in SSc ,26,27,28Dobutamine compared to exercise echocardiography has the advantage that it can be administered to patients unable to perform exercise due to orthopedic problems and it is technically less demanding. Dobutamine as a stressor increases CO by its inochronotropic action, and it has been suggested that it induces pulmonary vasodilatation. Lau et al.  applied Our study was based on the hypothesis that in the early stages of PAH, resting pulmonary pressure measurements may be normal or near normal due to the pulmonary vasculature reserve. However, dobutamine-induced increase in pulmonary blood flow may overcome the vasculature reserve, reveal a latent circulatory dysfunction, increase PAP, and unmask PH in SSc patients.The development of PH in SSc patients is multifactorial. Several factors may be implicated in resting or dobutamine-induced PH in SSc. Besides pulmonary vascular remodeling, diastolic dysfunction and interstitial lung fibrosis may be involved . In our The main limitation of our study is the relatively small sample size. Therefore, larger studies are needed to replicate our results and define the exact role of DSE in SSc patients. Another limitation is that DSE was used in a highly selected subgroup of SSc patients, and therefore its value for revealing PAH cannot be generalized for all SSc patients with equivocal resting echocardiography for PH.Low-dose DSE has a satisfactory diagnostic accuracy in revealing PAH in selected asymptomatic or oligosymptomatic patients with SSc whose resting echocardiography for PH is non-diagnostic. Therefore, it may be a useful “noninvasive” technique in SSc patients with low or low to intermediate probability of PAH and equivocal echocardiography for PH, particularly in hospitals without facilities for RHC. If DSE is suggestive of PAH, then RHC should be performed. However, it should be emphasized that DSE has no place as a diagnostic tool in SSc patients with intermediate-to-high or high probability of PAH who require referral to a PH clinic for RHC and initiation of appropriate treatment if PAH is confirmed.


Echocardiography and Doppler studies were performed before and after HD. The LV global longitudinal, circumferential and radial strains were measured with two and three-dimensional STI.after HD, LV dimensions, left atrium (LA) area, systolic pulmonary arterial pressure and inferior vena cava diameter decreased significantly. The peak mitral E velocity, the E/A ratio of the mitral inflow and the lateral E/E´ ratio decreased also significantly. The LV and LA volumes index and LV mass index (LVMi) decreased remarkably after HD. The 3D- LV and LA ejection fractions were unchanged after HD. Although, 3D-estimated LVEF seemed to be preserved in the HD patients, the 2D and 3D- strain rates were decreased in all directions. The global strain values improved in all directions after a single HD session. Inverse correlations were found between the LVMi, serum BNP and LV global longitudinal strain.in HD patients with preserved LV ejection fraction, the STI analysis may add important information concerning the subclinical LV dysfunction. Chronic kidney disease (CKD) is a worldwide public health problem, which is associated with an increased morbidity and cardiovascular diseases. As compared with healthy individuals, mortality is increased by 10- to 20- fold in hemodialysis (HD) patients . BecauseTDI is pretended to be a useful diagnostic method to detect the LV dysfunction and acute changes in LV function , 7. But,Study population: the study was performed in a tertiary care centre of cardiology between 01st May 2014 and 28th June 2014. We enrolled 30 chronic HD patients, who underwent maintenance HD treatment three times weekly. All patients were asymptomatic before inclusion. Patients with known coronary artery disease, cardiac arrhythmias, cardiomyopathy or severe valvular disease diagnosed by echocardiography were not included. All patients had preserved left ventricular ejection fraction (LVEF) of 50% or greater. All the study participants provided their consent before entering the study. After physical examination, different parameters were recorded for all patients before and after HD: height, weight, heart rate and blood pressure. Body surface area (BSA) was calculated by the Mosteller formula [ formula . Blood aStandard echocardiography: parasternal long-axis view was used for the M-Mode measurements of left atrial diameter, interventricular septal, LV posterior wall thickness (IVST and LVPWT), LV end-diastolic and end-systolic dimensions (LVEDd and LVESd). In addition, left atrial area and volume were determined. LV fractional shortening (LVFS) was calculated as (LVEDd - LVESd)/LVEDd. LV ejection fraction (LVEFs) was calculated from LV volumes by the modified biplane Simpson rule and expressed as a percentage.The pulsed Doppler transmitral flow velocity profile was obtained from the apical four-chamber view by the sample volume positioned below the mitral leaflets. Different parameters were evaluated: peak transmitral flow velocity in early diastole (E), peak transmitral flow velocity in late diastole (A), mitral A wave duration (dAm), E/A ratio, and the E deceleration time (DT). The isovolumetric relaxation time (IVRT) was measured with a recording simultaneous mitral filling flow and aortic ejection flow. Analysis of pulmonary venous flow was realised at the right superior pulmonary vein. The amplitude of the S (peak S), D (peak D) waves, the ratio S/D and the duration of Ap wave (dAp) were measured. The difference between the pulmonary and mitral A waves duration (dAp-Am) was determined.Doppler tissue imaging (TDI) was performed in the four-chamber view, with the mitral and tricuspid annular planes perpendicular to the ultrasound beam. Pulsed TD sample volume was placed at the septal and lateral aspects of the mitral annulus, and at the lateral aspect of the tricuspid annulus. Measurements were made of peak systolic (S), peak early diastolic (E´), and late peak diastolic myocardial velocities (A´), and the E´/A´ratio at the lateral mitral annulus. The color M-mode Doppler flow propagation velocity (Vp) was obtained by combined color-flow Doppler and TM-mode interrogation of the mitral inflow during diastole.Speckle tracking imaging and three-dimensional echocardiography analysis: for the tracing of the endocardium and epicardium, the following views were displayed: the apical four-chamber view, the apical two-chamber view, the apical three-chamber view and the three short-axis views, the apex of the LV, the midlevel of the LV, and the basal level of the LV. The LV endocardium and epicardium were traced automatically, and the tracings were refined with further adjustment. We performed two-dimensional strain analysis, including the global longitudinal strain (2D-GLS), radial strain (2D-GRS), and circumferential strain (2D-GCS) ((2D-GCS) . ECG-gat2 [To measure LV end- diastolic and end-systolic volumes (3D-LVEDV and 3D-LVESV), LA volume, LV ejection fraction (3D-LVEF) and mass, and to perform the 3D global strain analysis, dedicated software was used . The 3D LV mass (LVMi) was indexed to BSA. LV hypertrophy was defined as LVMi >91 g/m2 . At specStatistical analysis: statistical analysis was performed using Statistical Package for Social Sciences version 20.0 . Continuous variables with normal distribution were presented as the mean . Qualitative variables were given as percent. Correlations between continuous variables were assessed using Pearson´s or Spearman´s correlation analysis. To compare variables before and after HD, paired t test (for the parametric variables) and Wilcoxon test (for the non-parametric variables) were performed. A p-value under 0.05 was considered as statistically significant.Clinical characteristics: the baseline demographic and clinical features of the study population are summarized in MM and two-dimensional echocardiographic parameters: M-mode and two-dimensional echocardiographic changes are shown in Doppler parameters:Three-dimensional volumetric parameters and STI analysis: LV and LA end-diastolic and systolic volumes index and LV mass index decreased remarkably after HD. The 3D- LV and LA ejection fractions were unchanged after HD (3D- LVEF: 58.46 (7.14)% vs 58.90 (7.03)%, p = 0.74, 3D- LAEF: 37.66 (17.65) vs 39.65 (13.32), p = 0.53). Although, 3D-estimated LV ejection fraction seemed to be preserved in the hemodialysis patients, the 2D and 3D- strain rates were decreased in all directions. The global strain values improved in all directions after a single HD session ( session . LVEF wa session . InverseThe changes in cardiac function and structure remains incompletely characterized in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). In fact, the myocardial effects of uremia and HD are difficult to determine, because micro- and macro-vascular ischemia in CKD patients significantly deteriorates myocardial mechanics and results in LV remodelling , 13. FurIn this study, the systolic and diastolic LV functions throughout the cardiac cycle using standard TTE, Doppler, three-dimensional volumetric parameters and speckle tracking analysis were investigated before and after a single HD session in asymptomatic patients with apparently preserved LVEF. The main results of this study are: (1) the LV diastolic and systolic function were both impaired in HD patients; (2) although the global systolic LVEF estimated by conventional TTE methods seemed to be normal, longitudinal, radial and circumferential strain rates were decreased indicating that LV function was really impaired; (3) the LV volumetric parameters and function were improved after a single HD session.Our study showed that HD induced significant changes in diastolic LV function. In several previous studies, the HD induced significant decrease in peak E of the mitral inflow and E/A ratio without any significant changes of peak A and DT , 18, 19.et al. [et al. [et al. [et al. [et al. [In contrast, Abid et al. , Dincer  [et al.  and Agmo [et al.  related  [et al.  demonstr [et al. , in a st [et al. , 7, 19.  [et al. . In fact [et al. . These p [et al. . In anot [et al. . So that [et al. , 24.Nevertheless, TDI has some important limitations. Actually, if the angle of interrogation between the tissue motion and ultrasound beam is greater than 20°, the peak values will be significantly reduced. Additionally, TDI is unable to resolve the difference in motion of a myocardial segment that may be actively contracting or simply being displaced due to the tethering effect from the adjacent segment. Reverberations and side lobes can also introduce error that may overestimate or underestimate the myocardial deformation . So, moret al. [et al. [et al. [There were different responses to the strain analysis after HD. As comparable to our data, Kovács et al.  and Yan  [et al.  reported [et al. . Fagugli [et al.  showed t [et al. . This su [et al. .Study limitations: this study had several limitations. First of all, the relatively small number of patients may present a limitation for the validation of the efficiency of the methods and data. The temporal and spatial resolutions are relatively lower in the 3D-STI than in the 2D-STI. Therefore, several patients had to be excluded because the image quality in 1 or more segments was insufficient for the STI analysis. Furthermore, there was no control group to compare the different echocardiographic findings. Finally, our study was an observational study and did not include the long-term cardiovascular event rates or survival assessment of the HD patients, the relationship between the results and the cardiovascular prognosis didn´t be evaluated.In CKD asymptomatic patients with preserved LVEF, the STI analysis may add important information concerning the LV myocardial function. In fact, subclinical LV deformation and dysfunction exist in HD patients and STI offers a new tool to detect and predict the LV myocardial function changes. After a single HD treatment, the myocardial LV deformation improved in all directions. This could be due to optimal control of the volume fluid, blood pressure and a reduction in the LVM. Finally, the strain assessment may contribute to better vascular risk stratification and survival improvement in HD patients.Many clinical studies in medical literature evaluated the effects of hemodialysis on left ventricular myocardial systolic and diastolic functions;The echocardiographic findings remained controversial in the assessment of myocardial function, and identifying early subclinical changes in hemodialysis patients;The speckle tracking echocardiography is a relatively new non-invasive imaging technique that allows an objective assessment of the regional and global myocardial function.The present study highlights the importance of the echocardiographic study to detect progressive changes in the hemodialysis patients before and after a single hemodialysis session;The conventional echocardiography can detect some differences in hemodialysis patients but it is incapable to reveal differences in intrinsic myocardial functions: thereby, the evaluation of speckle tracking echocardiography can be useful for identifying previously undetected differences and subclinical changes before and after a single hemodialysis session. The present study showed the 2D and 3D- strain rates were decreased in all directions in the study population; the global strain values improved in all directions after hemodialysis; inverse correlations were found between the left ventricular mass index, serum BNP and left ventricular global longitudinal strain;Considering our results and the large heterogeneity of echocardiographic pattern generally found in hemodialysis, several possible clinical applications of deformation parameters approach can be advised.


Background and Objectives: Resistance to ASA (ASAres) is a multifactorial phenomenon defined as insufficient reduction of platelet reactivity through incomplete inhibition of thromboxane A2 synthesis. The aim is to reassess the prevalence and predictors of ASAres in a contemporary cohort of coronary artery disease (CAD) patients (pts) on stable therapy with ASA, 75 mg o.d. Materials and Methods: We studied 205 patients with stable CAD treated with daily dose of 75 mg ASA for a minimum of one month. ASAres was defined as ARU (aspirin reaction units) ≥550 using the point-of-care VerifyNow Aspirin test. Results: ASAres was detected in 11.7% of patients. Modest but significant correlations were detected between ARU and concentration of N-terminal pro-brain natriuretic peptide (NT-proBNP) , body weight, body mass index, red blood cell distribution width, left ventricular mass, and septal end-systolic thickness, with trends for left ventricular mass index and prothrombin time. In multivariate regression analysis, log(NT-proBNP) was identified as the only independent predictor of ARU—partial r = 0.15, p = 0.03. Median concentrations of NT-proBNP were significantly higher in ASAres patients  and right ventricular diameter was larger, whereas mean corpuscular hemoglobin concentration was lower as compared to patients with adequate response to ASA. Conclusions: ASAres has significant prevalence in this contemporary CAD cohort and NT-proBNP has been identified as the independent correlate of on-treatment ARU, representing a predictor for ASAres, along with right ventricular enlargement and lower hemoglobin concentration in erythrocytes. Modulation of thrombocytes’ reactivity with antiplatelet drugs has become a cornerstone of modern cardiovascular pharmacotherapy. Conversion of arachidonic acid to thromboxane A2 (TXA2) by cyclooxygenase-1 (COX-1) enzyme contributes to proper platelet aggregation. This enzyme catalyzes the synthesis of prostaglandin H2 from arachidonic acid, further converted to TXA2 by TXA2 synthase. Aspirin (ASA), a commonly used antiplatelet, irreversibly blocks COX-1 by acetylation of serine at position 529 of COX-1, modifying the catalytic center of the enzyme and preventing binding of arachidonic acid. However, ASA does not produce a sufficient antiplatelet effect in all patients. In the case of resistance to ASA (ASAres), TXA2 synthesis is not sufficiently inhibited and residual risk of thrombus formation in coronary arteries remains ,4. CurreWe decided to analyze the correlation of ASAres with echocardiographic parameters due to the previously described relationship of ASAres with body weight and multiple risk factors for atherosclerotic heart disease. Previous publications have confirmed the relationship between body weight, BMI and left ventricular mass index (LVMI) .The aim of our study was to assess the prevalence of ASAres in patients with coronary artery disease (CAD) chronically treated with standard ASA dose, to study the correlation of on-treatment ARU with clinical and echocardiographic variables and to identify potential predictors of ASAres.This prospective single-center study recruited 205 patients  hospitalized in our department from October 2018 to February 2019 with diagnosed stable CAD. The patients’ flow diagram is shown in All patients were treated with a stable regimen of 75 mg ASA o.d. for a minimum of one month following current guidelines—directed coronary artery disease medical therapy . ExclusiWe measured ASAres using VerifyNow  point-of-care platelet function analyzer ,15. The We compared atherosclerotic risk factors , the history of treatment and comorbidity profiles in both groups. Blood tests including lipid panel, creatinine, glucose, hemoglobin A1c (HbA1c), N-terminal pro-brain natriuretic peptide (NT-proBNP), C-reactive protein (CRP), coagulogram and morphology were performed on an empty stomach using the standard method in appropriate test tubes.The echocardiographic studies were performed by the same team of the echocardiographic laboratory in I Department of Cardiology Medical University of Lodz according to guidelines of the Echocardiography Section of the Polish Cardiac Society, and we measured standard diameters of cardiac cavities, left ventricular end-diastolic diameter (LVEDD), posterior wall end-diastolic thickness (PWTd) and interventricular septal end-diastolic thickness (IVSTd); left ventricular mass (LVM) and (LVMI) were calculated . Due to p-value, with a p-value less than 0.05 accepted as significant. We analyzed the relationships between ARU and the independent clinical variables  using Spearman’s coefficient of rank correlation. Multivariate regression analysis was applied to determine the relationship between ASAres and independent risk factors.We analyzed the data using MedCalc Statistical Software version 12.2.1.0 . We used the D’Agostino–Pearson’s test to confirm the normal distribution of data. We used the independent samples t-test or Mann–Whitney test as non-parametric equivalent to confirm the differences between the subgroups of ASAres and ASAsens patients. The chi-square test was used to test the statistical significance of associations between categorical variables. We used the normal approximation  to calculate the 2. The study group characteristics regarding the entire study cohort and the subgroups defined by the presence or absence of ASAres are presented in Median values for ARU in the study group were 427 (range 327–660) and the prevalence of ASAres was 11.7% (24/205 pts). We included 36.6% females, average age 68.2 (9.7) years, average BMI 27.3 (4.6) kg/mWe identified several novel correlates of ASAres which can contribute to better understanding of the significant phenomenon of aspirin resistance. On-treatment ARU values showed multiple correlations with studied clinical data as shown in n = 205), the only independent predictor of ARU was log(NT-proBNP)—partial r = 0.15, p = 0.03. With echocardiographic data included in the multivariate analysis (n = 186), the optimal model  was composed of three independent predictors for ARU: log(NT-proBNP), body mass and interventricular septal end-systolic thickness.In multivariate regression analysis excluding echocardiographic data  in ASAres patients. The ROC curve for log(NT-proBNP) presents the area under the curve AUC = 0.625  with a threshold value of 2.51 providing sensitivity of 75.0% and specificity 51.4%, negative predictive value of 94.0% and positive predictive value of 17.0% for ASAres. VerifyNow tests are used as screening tests for patients with ASAres. Our study confirms that non-elevated NT-proBNP is correlated with low likelihood of ASAres.Mann–Whitney’s test showed that median NT-proBNP concentrations were significantly higher  MCHC. The main finding of our study is identification of ASAres rate in the contemporary population of Polish CAD patients and possible association of ARU measured on treatment with 75 mg ASA per day with natriuretic peptides and RVD. ASAres has been identified in the population with stable CAD  and is oNT-proBNP value is associated with heart failure. Previous research showed that the incidence of aspirin resistance increased in patients with chronic heart failure (CHF) and decompensated type 2 diabetes mellitus (DM2). PLUTO-CHF trial observed higher platelet activity in patients with CHF treated with ASA ,21. HoweThe process of heart failure is connected with the renin–angiotensin–aldosterone system (RAAS) activation, which contributes to increased synthesis of angiotensin II. We can assume that activation of TXA2 is stimulated by angiotensin II. Thromboxane A2 promotes platelet aggregation through the thromboxane prostanoid (TP) receptor and this overstimulation may be linked to aspirin resistance . The schSome studies have shown the decrease of platelet aggregation by angiotensin converting enzyme (ACE) inhibitors. The inhibition of TXA2 synthesis was demonstrated for captopril and fosinopril ,26,27. SWe found a correlation between on-treatment ARU value and LVM which can, therefore, be hypothetically linked to increased TXA2 activity in ASAres patients—it was demonstrated that the TP receptor mediates angiotensin II-dependent hypertension and left ventricular hypertrophy in mouse model .Our research showed that proximal right ventricular outflow tract diameter was correlated with aspirin resistance. Increased isoprostane (8-isoPGF2α or 8-isoF), an oxidative stress marker, is connected with right ventricular dilatation and heart failure. One of the hypotheses regarding aspirin resistance is based on the non-enzymatic effect of isoprostane on thromboxane A2 receptors on the platelet surface. Despite inhibition of TXA2, platelets activated by TP receptor and platelet aggregation continue despite treatment with ASA. It may be suggested that increased oxidative stress can lead to sustained platelet activity independent of the blocked COX-1 pathway . Beside During aspirin treatment, special attention should be paid to patients with heart failure and obesity—we did not study these but they are common. We can assume that pill formulations may influence bioavailability of ASA. Evidence exist that aspirin with enteric coating may limit the efficacy of aspirin.  Other apStudy design was a single center and subject count was moderate. Proximal RVOT was chosen as the only RV size marker because of its common use in community echocardiographic laboratories in Poland. Platelet function is a complex activity and alternative tests can be used for assessing reactivity—for practical reasons we decided to use only one simple yet clinically applicable point-of-care-specific test. Close to 30% of our patients received dual antiplatelet therapy which could represent an additional confounding factor. We did not analyze specific ASA formulation but enteric-coated pills represent the vast majority of formulation used in secondary prevention in Poland.The prevalence of ASAres in a contemporary cohort of patients with coronary disease treated with 75 mg daily ASA dose was 11.7%. We identified NT-proBNP as the only independent correlate of on-treatment ARU, and a predictor for ASAres, along with right ventricular enlargement and lower hemoglobin concentration in erythrocytes. The relationship of thrombocytes’ response to ASA in patients with heart failure warrants further studies in the clinical setting.


The correlation analysis showed a statistically significant positive correlation between the RV/LV ratio and CTR . Based on the ROC curves, CTR values were determined as the optimal cut-off points for the prediction of right ventricular enlargement (RV/LV ≥ 0.9 or RV/LV ≥ 1.0), being 0.54 and 0.55, respectively. The sensitivity, specificity, and accuracy of the CTR criterion >0.54 as a predictor of RV/LV ratio ≥0.9 were 0.412, 0.963, and 0.656, respectively, while those of the CTR criterion >0.55 as a predictor of RV/LV ratio ≥1.0 were 0.488, 0.833, and 0.590, respectively. In summary, in patients with suspected pulmonary embolism during COVID-19, the radiographic cardiothoracic ratio can be considered as a prognostic factor for right ventricular enlargement, especially as a negative predictor of right ventricular enlargement in the case of lower CTR values.The aim of the study was to determine the usefulness of the radiological cardiothoracic ratio (CTR) as a predictor of right ventricular enlargement in patients with suspected pulmonary embolism during COVID-19. The study group consisted of 61 patients with confirmed COVID-19, suspected of pulmonary embolism based on physical examination and laboratory tests (age: 67.18 ± 12.47 years). Computed tomography angiography (CTA) of pulmonary arteries and chest radiograph in AP projection with cardiothoracic ratio assessment were performed in all patients. Right ventricular enlargement was diagnosed by the ratio of right ventricular to left ventricular (RV/LV) dimensions in pulmonary CTA with two cut-off points: ≥0.9 and ≥1.0. Heart silhouette enlargement was found when CTR on the chest radiograph in the projection AP > 0.55. The mean values of RV/LV and CTR in the studied group were 0.96 ± 0.23 and 0.57 ± 0.05, respectively. Pulmonary embolism was diagnosed in 45.9%. Right ventricular enlargement was documented in 44.3% or 29.5% depending on the adopted criterion RV/LV ≥ 0.9 or RV/LV ≥ 1.0. Heart silhouette enlargement was found in 60.6%. Patients with confirmed pulmonary embolism (PE+) had a significantly higher RV/LV ratio and CTR than patients with excluded pulmonary embolism (PE−) (RV/LV: PE+ 1.08 ± 0.24, PE− 0.82 ± 0.12; CTR: PE+ 0.60 ± 0.05, PE− 0.54 ± 0.04;  The virus SARS-CoV-2 causes a complex of symptoms of a viral respiratory infection, in severe cases causing acute respiratory failure and death . During In its natural course, pulmonary embolism causes more or less intensive overload of the right cardiac ventricle. It is estimated that about 45% patients with acute pulmonary embolism will develop right ventricular insufficiency , and as Apart from the pulmonary embolism, the right ventricular enlargement may cause pulmonic valve stenosis, pulmonary hypertension, arterial and/or ventricular septal defects, tricuspid valve regurgitation, hypertrophic cardiomyopathy, congenital defects, etc. An assessment of the RV size and functions can be made via echocardiography, computed tomography and magnetic resonance ,16,17. AA test of choice, characterized by high sensitivity and specificity for diagnosing acute pulmonary embolism is pulmonary artery computed tomography angiography (CTA) . Apart fThe cardiothoracic ratio is an easy to calculate indicator in the assessment of myocardial enlargement. It is defined as the ratio of the largest transverse heart dimension to the largest transverse chest dimension, measured to the internal rib surface on a chest radiograph . Any valThe purpose of the study was to determine the usefulness of the cardiothoracic ratio (CTR) as a predictor of right ventricular enlargement in patients with suspected pulmonary embolism secondary to COVID-19.Betacoronaviridae using the qRT-PCR method), an increased concentration of D-dimers in the blood, a clinically indicated CTA of the pulmonary arteries and an AP chest radiograph performed within 48 h. The criteria of exclusion in the study were as follows: an ambiguous result of the pulmonary artery CTA scan, a diagnosed pulmonary or mediastinal carcinoma, large amounts of fluid in the pleural cavity/cavities, fluid present in the pericardial sac. The anthropometric parameters of the study group of patients are presented in The study group consisted of 61 patients with confirmed COVID-19, in which pulmonary embolism was suspected based on a physical examination and laboratory tests. Group size was determined using a sample size calculator. The selection conditions were as follows: population size 2 million, fraction size 0.2, maximum error 10%, confidence level 95%. The required minimum size of the study group was 61. The criteria of inclusion in the study were as follows: age ≥ 18 years, a positive result of a nasopharynx smear test against SARS-CoV-2 .The methodology of the study comprised an analysis of the basic anthropometric parameters and the following diagnostic images: AP chest radiograph (CR) and computed tomography angiography (CTA) of the pulmonary arteries.According to the adopted criteria of inclusion in the study, the interval between the pulmonary artery CTA and the AP chest radiograph did not exceed 48 h. In case more than one CR was acquired within 48 h before or after the pulmonary artery CTA, the analysis was performed using the chest radiograph acquired within the shortest interval from the pulmonary artery CTA.On account of the clinical condition of the patients, chest radiographs were acquired in the lying position, in the anterior–posterior projection (AP), using a bedside X-ray machine. Radiographs were acquired, as far as possible, while the patient was holding their breath, with maximum inhalation, using the X-ray lamp set at 120 kV.The cardiothoracic ratio (CTR) was assessed using a diagnostic station conforming to the legal regulations for radiologic tests. The maximum cardiac width (C width) and the maximum thoracic width (T width) were measured. The value of the cardiothoracic ratio was calculated using the following formula: CTR = C width/T width. Enlargement of the heart silhouette was diagnosed if, in the AP chest radiograph, the CTR > 0.55. An example of the CTR measurement in the AP chest radiograph is presented in CTAs of the pulmonary arteries were acquired using a 64-slice computed tomography scanner SOMATOM Definition AS+ , in accordance with the standard protocol. In this protocol, the sequence of actions was as follows: tomograph, pre-monitoring and monitoring with the ROI set within the pulmonary trunk/left pulmonary artery at the tracheal bifurcation level, and the proper acquisition with a start triggered by the contrast saturation of 100 HU within the ROI. The acquisition encompassed the area from the pulmonary apices to the costophrenic angles. The exposure kilovolt value was 120 units, with variable mAs values. The scans were performed using intravenous contrast with a constant volume of 60 mL non-ionic contrast, infused with an automatic syringe into the cubital fossa veins, at the infusion rate of 4.0 mL/s. Basic reconstructions were made in axial planes, in 3.0 mm and 0.75 mm slices, along with secondary reconstructions MPR and MIP in frontal and sagittal planes.The pulmonary artery CTA images required for this analysis were assessed using an application for post-processing of computed tomography images, syngo.CT Cardiac Function , by two staff radiologists experienced in the assessment of cardiac and vascular angiography images. Pulmonary embolism (PE+) was diagnosed in cases where filling defects in the pulmonary arteries were found. To assess right ventricle enlargement, the size of both ventricles was measured. The size of the right and left ventricle (RV diameter and LV diameter) was measured based on a multiplanar reconstruction (MPR), in a four-chamber projection, perpendicularly to the long axis of the ventricles, at 1/3 distance between the mitral valve and the apex. The diameter of a ventricle was recognized as the distance between the endocardium of the free wall of the ventricle and the endocardium of the interventricular septum. The papillary muscles were included in the lumen of the chamber. Each time, the average measurement result was considered the final RV diameter and LV diameter values. At the time of the measurement, the radiologists assessing the ventricle dimension had no knowledge of the CTR value. Enlargement of the right ventricle was diagnosed based on the ratio of the right and left ventricle size (RV/LV) in the pulmonary artery CTA, using two different cut-off points: ≥0.9 and ≥1.0. An example of measuring the RV/LV ratio in the pulmonary artery CTA is presented in p < 0.05.Statistical analysis was performed using the Dell Statistica 13  application. For quantitative variables, arithmetic means and standard deviations were calculated. The Shapiro–Willke test was used to verify normal distribution of the variables. Quantitative independent variables with normal distribution were further analyzed using a t test for independent variables. Variables with distribution other than normal were analyzed using the U Mann–Whitney test for independent quantitative variables. Results for the qualitative variables were expressed as a percentage. Qualitative variables were analyzed using the chi-square test. Correlation was analyzed to specify the relationship between the analyzed variables. Pearson correlation coefficients were determined for quantitative variables with normal distribution, and Spearman correlation coefficients for quantitative variables with distribution other than normal. Moreover, the accuracy was tested, with proposed cut-off points for the tests estimated based on the ROC (receiver operating characteristic) curves. The adopted statistical significance level was The average CTR value in the study group of the patients was 0.57 ± 0.05. Radiological enlargement of the heart silhouette was diagnosed in 60.6% of the subjects. Based on the CTA of the pulmonary arteries, pulmonary embolism was diagnosed in 45.9% of the subjects. The average RV/LV ratio was 0.96 ± 0.23. Right ventricle enlargement, depending on the adopted criterion of RV/LV ≥ 0.9 or RV/LV ≥ 1.0, was documented in 44.3% or 29.5% of subjects. The results of the heart silhouette measurement by a chest radiograph and the results of the analyzed variables in the pulmonary artery CTA in the examined group of patients with suspected pulmonary embolism secondary to COVID-19 are presented in A comparative analysis of the subgroups divided on the basis of the CTR cut-off point of 0.55 demonstrated that the patients with enlarged heart silhouette were characterized by statistically significantly higher values of the RV/LV in the pulmonary artery CTA than the patients with non-enlarged heart silhouette; they also significantly more often met the criteria of right ventricle enlargement (both defined as RV/LV ≥ 0.9 and as RV/LV ≥ 1.0). The selected variables of the pulmonary artery CTA in the study subgroups divided on the basis of the criterion of enlarged heart silhouette in the chest radiograph are presented in When comparing the subgroups divided on the basis of the cut-off points RV/LV ≥ 0.9 and RV/LV ≥ 1.0, it was documented that the patients with an enlarged right ventricle had statistically significantly higher CTR values than those with non-enlarged right ventricles. In patients with enlarged right ventricle, the heart silhouette enlargement (defined as CTR > 0.55 in the AP chest radiograph) was observed statistically significantly more often than in patients with non-enlarged right ventricle. The size of the heart silhouette in CR of study subgroups divided on the basis of the criterion of right ventricle enlargement in the pulmonary artery CTA is presented in In a comparison of the subgroups divided on the basis of diagnosed pulmonary embolism, it was found that the patients with confirmed pulmonary embolism had statistically significantly higher CTR and RV/LV than those with excluded pulmonary embolism. In the patients with confirmed pulmonary embolism, enlarged heart silhouette was found statistically significantly more often than in those with excluded pulmonary embolism. These study subgroups demonstrated no differences in the frequency of enlarged right ventricle in the pulmonary artery CTA. The size of the heart silhouette in CR and the selected variables of the pulmonary artery CTA in the study subgroups divided on the basis of the criterion of pulmonary embolism diagnosed in the pulmonary artery CTA are presented in p < 0.05), , .The demonstrated correlation occurred in all the divided subgroups, except for the group with excluded pulmonary embolism. The results of an analysis of the heart silhouette size in the chest radiograph and the size of the right ventricle in the pulmonary artery CTA in the whole study group and study subgroups are presented in The ROC curves were used to determine CTR values constituting optimal cut-off points for the prediction of right ventricle enlargement (RV/LV ≥ 0.9 or RV/LV ≥ 1.0), amounting to 0.54 and 0.55, respectively A,B.The sensitivity, specificity, and accuracy of CTR > 0.54 as a predictor for RV/LV ≥ 0.9 were 0.412, 0.963, and 0.656, respectively, while those of CTR > 0.55 as a predictor for RV/LV ≥ 1.0 were 0.488, 0.833, and 0.590, respectively. The test accuracy analysis indicated that the predictors had a significantly higher specificity than sensitivity. The results of the accuracy analysis for the radiological cardiothoracic ratio as a predictor of right ventricle enlargement in the pulmonary artery CTA for the whole study group are presented in COVID-19 has become an enormous epidemiological problem for the entire world; we witnessed as numerous health care systems in many countries around the globe collapsed one by one. Apart from acute respiratory failure secondary to pneumonia, this illness involves numerous complications, including cardiovascular ones. In 28 out of the 61 patients in the investigated group, the pulmonary artery CTA scan demonstrated the presence of pulmonary embolism (45.9%), which confirms the weight of the problem in patients hospitalized with diagnosed COVID-19. Similar percentages of pulmonary embolism were reported by researchers from Italy (44.7%)  and LondDimensioning of the right ventricle is reflected in the guidelines regarding the diagnostics and treatment of pulmonary embolism, and the RV/LV ratio may be a prognostic factor . To asseAccording to our data analysis, such determined CTR can be considered as a prognostic factor for right ventricular enlargement in patients with pulmonary embolism secondary to COVID-19. RV/LV was significantly higher in patients with enlarged heart silhouette than in patients with non-enlarged heart silhouette. CTR was significantly higher in patients with an enlarged right ventricle (higher RV/LV) than in patients with non-enlarged right ventricles (lower RV/LV). There was a positive correlation between RV/LV and CTR. In addition, the accuracy of CTR > 0.54 as a predictor for RV/LV ≥ 0.9 was 65.6%. However, considering that the specificity of prediction is much higher than its sensitivity (over 80% compared to less than 50%), especially lower CTR values may indicate a lack of right ventricular enlargement in patients with COVID-19. The high sensitivity of prediction always indicates the usefulness of the test in confirming a given state, while the high specificity of prediction indicates the usefulness of the test in excluding a given state.The research published so far also confirms our observations, although the number of these studies is small. Researchers from Iran proved that CTR determined during a chest CT is a strong predictor for mortality in patients with COVID-19, and its values grow together with the affected volume of the pulmonary parenchyma. Just like us, the researchers demonstrated that over half of the patients had increased CTR; in our group it was 60.6% . ConsideResearchers from Warsaw reached different conclusions, when they failed to prove a significant CTR value in predicting the right ventricle size in a different group of patients, namely those after a Fallot tetralogy correction . The samThe Iranian researchers, while indicating significantly lower value to estimating heart size using CTR than using echocardiography, at the same time emphasized the prevalence of the radiographic method and cited it as a good, low-cost screening assessment for heart silhouette enlargement .Our study was encumbered by several limitations, which still fail to significantly reduce the value of the results. In terms of the studied group, the limitations included the small size of the study group, the lack of data on pharmacotherapy for chronic diseases, as well as the inability to perform analyses in subgroups of patients with specific comorbidities . The results of the present study are a starting point for further studies on a larger group of patients, which will allow consideration for the importance of comorbidities, as well as their pharmacotherapy. In terms of the research methodology itself, the following limitations should be mentioned. The study did not consider the volume of the pulmonary parenchyma affected by the inflammation, while from a pathophysiological perspective, an increase in the affected volume of the pulmonary parenchyma would increase the afterload of the right ventricle, which may cause an enlargement of the right ventricle, and, in consequence, the CTR. Therefore, these data should be related to the volume of the lungs affected by the inflammation, particularly in the group of patients without diagnosed pulmonary embolism, but with a diagnosed enlargement of the right ventricle or CTR. Additionally, determination of the CTR on an AP radiograph has numerous limitations. Due to the health condition of the patients in the study group, it was not possible to perform a PA radiograph; therefore, it appears that comparing the CTR measurement to the CTR determined in pulmonary CTA could provide added value. Moreover, we had no access to chest radiographs or chest CT scans of the patients that were taken before current hospitalization. It seems that excluding patients with prior CTR and RA/LV increases from the study group could improve the sensitivity and specificity of the assessment for the investigated parameters in the context of pulmonary embolism secondary to COVID-19. Finally, the pulmonary artery CTA was only performed on patients with suspected pulmonary embolism instead of the whole group, making it impossible to determine the number of patients with clinically silent pulmonary embolism.In patients with suspected pulmonary embolism secondary to COVID-19, the radiological cardiothoracic ratio can be considered as a prognostic factor for right ventricular enlargement. Considering that the specificity of prediction is much higher than its sensitivity, especially lower CTR values may indicate a lack of right ventricular enlargement in patients with COVID-19.