Patients with paroxysmal AF were also likely to have larger left atrial volume and a higher peak tricuspid regurgitation velocity, leading to higher prevalence (though <10% in the AF group) of diastolic dysfunction . Multivariable conditional logistic regression models showed that paroxysmal AF was significantly associated with increased left ventricular mass and left atrial enlargement , but not with e’ and deceleration time of E wave . Conclusions: Left ventricular mass and left atrial enlargement rather than diastolic dysfunction  were associated with paroxysmal AF irrespective of body mass index, blood pressure and renal function. These findings suggest that cardiac remodeling may occur very early in the natural history of AF.Background: Atrial fibrillation (AF) leads to the development of cardiac remodeling/diastolic dysfunction and vice versa. We intended to determine whether cardiac remodeling/diastolic dysfunction is present at early stages of AF. Methods: We studied 175 patients with paroxysmal AF, compared with 175 matched control subjects, who had available echocardiography data to investigate the association between echocardiographic variables and AF from the STANISLAS cohort. Results: In this study , patients with paroxysmal AF had greater left ventricular mass compared to matched controls ( Atrial fibrillation (AF) is the most common arrhythmia. It is associated with incident heart failure (HF), and with its progression . It has AF causes the progressive development of left atrial (LA) remodeling, particularly when AF is persistent. Patients with pre-existing structural cardiac abnormalities such as LA enlargement are likely to have a high incidence of AF, especially in subjects with cardiovascular risk factors or in patients with HF. Thus, AF and atrial enlargement are inter-related in a deleterious loop. Their common background and associated risk factors  suggest that they share etiologies . However2  were significantly associated with paroxysmal AF whereas e’ and DT were not  [OR(95%CI) = 4.52 (2.05–9.97), were not . The curwere not  though iwere not .In this study, only 10% of patients with paroxysmal AF had DD as defined by the recent recommendations. The independent differences in echocardiographic variables between patients with paroxysmal AF and controls were related mainly to LV/LA remodeling and increased TR, rather than to e’ velocities or E/e’. Since the groups had similar hypertension status and systolic blood pressures, we could disregard any influence of increased afterload. The much higher prevalence of atrial and ventricular remodeling, rather than DD, suggests that LV hypertrophy and LA enlargement may precede persisting AF rather than being the ultimate consequence of persisting AF. This finding may be the consequence of atrial myopathy being both the substrate and the outcome of atrial fibrillation ; followiYet, we did also identify LV hypertrophy as being more frequent in paroxysmal AF, which suggests that pathophysiological processes going beyond the atria are involved in a number of patients. This finding is in line with the report of Seko et al., reporting an increased prevalence of AF appears with increasingly abnormal LV remodeling patterns .Our study could also support the concept that paroxysmal AF precedes the development of DD in most patients with paroxysmal AF, at least when DD is defined using the cut-points for e’ velocities and E/e’ proposed in the 2016 recommendations. Indeed, a minority of patients with AF had DD (<10%), which suggests that DD (as defined by the current echocardiographic definition) is hardly present in this population. The e’ velocity was abnormal in only 23.1% of the patients with paroxysmal AF, and none had an abnormal E/e’ index.Although the prevalence of DD, LA remodeling and LV remodeling were different in our cohort, the associations of all three parameters with AF in the multivariable model were similar (OR ~5). Another intriguing point is the greater difference in TR velocity than in mitral flow or myocardial velocities between paroxysmal AF and controls, suggesting that an increased TR velocity might be clinically useful, albeit infrequent, and may constitute an early sign of disease rather than just a late consequence of chronically elevated LV filling pressures. A growing body of evidence suggests that, not infrequently, isolated functional TR is concomitant to AF and right atrial remodeling . This fuThe main strengths of our study are the use of research-quality echocardiography in a community-based cohort (STANISLAS), and the refined methods (matching and adjustment) used to evaluate the association of echocardiographic variables with paroxysmal AF. However, it is a single-center study of patients referred for ablation of paroxysmal AF, who are not representative of the much broader population of all patients with AF. In addition, TR and DD could not be included in the multivariable analysis because the number of subjects with these parameters was small. We applied the most recent definition of DD, but have emphasized how changing definitions strongly influences the proportion of patients who are diagnosed as abnormal . Other dIn the current study, LA enlargement and LV hypertrophy, rather than LV diastolic dysfunction, are associated with paroxysmal AF, irrespective of hypertension history, blood pressure, eGFR and BMI. We found also that very few patients with AF fulfill the current criteria for DD. These results suggest that cardiac remodeling occurs very early in the natural history of AF, before it progresses from paroxysmal to persistent AF and before the development of DD.


Surgical ventricular restoration (SVR) leads to functional improvement by volume reduction and restoration of left ventricular (LV) geometry. Our purpose was to refine the planning for SVR using cardiac computed tomography (CCT).The possibility to anticipate the postoperative residual LV volume was assessed using CCT in 205 patients undergoing SVR combined with coronary artery bypass grafting (77%), mitral valve repair/replacement (19%) and LV thrombectomy (19%). The potential of CCT to guide the procedure was evaluated. Additionally, the predictive value of CCT characteristics on survival was addressed.2, 74–114 ml/m2 and >114 ml/m2; postoperative: <58 ml/m2, 58–82 ml/m2 and >82 ml/m2. On average, a 50 ml/m2 increase of preoperative LVESVI was associated with a 35% higher hazard of death (p = 0.043). Aneurysms limited to seven antero-apical segments . LVESVI predicted by CCT was found to correlate significantly with effectively achieved LVESVI .30-day, 1- and 5-year survival was 92.6, 82.7, and 72.1%, respectively, with a marked reduction of NYHA class III-IV quota after surgery (95.1% vs. 20.5% in the follow-up). Both pre- and postoperative LV end-systolic volume index (LVESVI) were predictive of all defined endpoints according to the following tertiles: preoperative: <74 ml/mCCT-guided SVR can be performed with good mid-term survival and significant improvement in HF severity. CCT-based assessment of achievable postoperative LV volume helps estimate the probability of therapeutic success in individual patients. Chronic ischemic heart failure (HF) after myocardial infarction (MI) is an important indicator of poor prognosis despite advances in drug and device therapy . The devSurgical ventricular restoration (SVR) of anterior LV aneurysms –11 is anThe analysis of LV volume, scar localization and extension as well as the amount of geometrical distortion play a key role in the preoperative assessment for SVR. Image guidance and a tailored surgical procedure are of paramount importance for a successful SVR. With its high spatial resolution of up to 0.4 mm and an acceptable time resolution of up to 75 ms, cardiac computed tomography (CCT) enables the analysis of a primarily acquired three-dimensional data set, the detailed examination of the cardiac anatomy and the assessment of the functional and geometrical remodeling of the cardiac chambers, based on exact true volume detection, with very high accuracy  can be successfully achieved using the volumetric, geometric and functional tools of CCT. We analyzed our single-center early and mid-term results and the factors determining survival and improvement in HF symptoms after CCT-guided SVR for anterior LV aneurysms.Using a modified Dor technique in most cases, SVR was performed in patients with severe HF symptoms, well-defined antero-septal LV akinesia or dyskinesia and preserved contractility of residual myocardium after anterior MI. The procedure was combined with coronary revascularization, MV repair or replacement and LV thrombectomy, when indicated. Endpoints were 30-day mortality, death from any cause in the follow-up period, implantation of a LV assist device and heart transplantation.The diagnosis of LV aneurysm was made by echocardiography or angiography and confirmed by CCT. Echocardiography and CCT were repeated during the first postoperative week. The pre- and postoperative data were analyzed and compared retrospectively. Clinical, demographic and procedural data were retrospectively collected.We retrospectively analyzed the data of 205 consecutive patients with coronary artery disease who underwent SVR for anterior LV aneurysms in our hospital between November 2005 and January 2016. All patients had a previous anterior MI with severe LV systolic dysfunction and symptomatic HF.Written informed consent for surgery was obtained from all patients or their representatives. The study was performed according to the principles of the Declaration of Helsinki and approved by the ethics committee of the Charité – Universitätsmedizin Berlin (EA2/177/20).All SVR procedures were performed through a median sternotomy approach under cardiopulmonary bypass (CPB). After coronary artery bypass grafting (CABG), LV repair and MV repair or replacement were performed. Antero-apical SVR was routinely performed using a modified Dor procedure with several Fontan sutures along the aneurysm perimeter without patch application to exclude the aneurysm and restore LV geometry . This teIntraoperative transesophageal echocardiography was routinely performed to assess the adequacy of LV repair. Mitral surgery was performed in patients with echocardiographically proven MR grade ≥2. All surgeons had access to the complete preoperative CCT assessment.CCT measurements have been extensively described previously . The datLV end-diastolic and end-systolic volume  were obtained  and thenTo separate the aneurysm volume in diastole and systole, a plane determined by three landmarks on the borders of scarred to intact LV myocardium  was used. The residual volumes were then assessed using the same CCT evaluation software tool . This enLocal WMA were estimated semiquantitatively using a 17-segment model with separate assessment of papillary muscles. Akinetic or dyskinetic segments involved in an aneurysm or scar formation of other localizations were detected.Automated cluster analysis was performed to establish the different scar patterns. The identified clusters were then tested for their influence on survival after SVR.Patients were divided into defined subgroups according to their LVA localization and extension: antero-apical LVA —subgroup1; antero-apical and basal septal or basal anterior LVA (plus segments 1 or 9)—subgroup 2; antero-apical LVA and additional scar of any other localization—subgroup 3.Morphological characteristics of the aneurysm in terms of myocardial disruption, apposition of thrombotic masses and pericardial effusion were also evaluated.The systolic and diastolic LV volumetric sphericity index (LVSI) was calculated on the basis of end-diastolic and end-systolic LV volume and LV long axis length in two-chamber view according to the empiric formula  Figure ,The left atrium (LA) volume was calculated at the end systole on the basis of planimetric measured LA area in two-chamber view (A1) and four-chamber view (A2) and LA length (L) according to the simplified empiric formula  Figure ,Follow-up was performed in 94.6% of the cases, either during a routine clinical evaluation in our outpatient department or by telephone contact using the short form Health Survey (SF-12) . In patit-test. Categorical variables are presented as numbers with percentages and compared using chi-square tests. Actuarial survival curves were produced using the Kaplan-Meier analysis with a long-rank test. For the evaluation of survival differences dependent on LV volumetric parameters, the patient population was subgrouped according to tertiles of LVESVI with further application of survival analysis. A cluster analysis of scarred ventricle segments detected in CCT was performed using nearest neighbor algorithm to reveal patterns of segmental wall motion abnormalities associated with better or worse survival.Continuous variables are presented as mean ± SD. Parametric and non-parametric tests were used where required. For parametric variables, means were compared with the paired, two-tailed student p-value <0.05 was considered statistically significant. The data were analyzed with SPSS 23 .Cox proportional hazard regression modeling was applied, and both univariable and multivariable hazard ratios were calculated to assess independent predictive factors of combined endpoint of all-cause mortality, implantation of a LV assist device and heart transplantation. A Preoperative patient characteristics are presented in A modified Dor procedure without patch application was performed in 180 patients (87.8%). while 25 patients underwent SVR with patch. One hundred and fifty eight patients (77.1%) had associated myocardial revascularization. Thirty nine patients (19%) underwent concomitant MV surgery (MV repair in 35 and MV replacement in four patients). LV thrombectomy was performed in 39 patients (19%).n = 9), septic shock (n = 4), electromechanical dissociation (n = 1) or stroke (n = 1). The operative and postoperative data are summarized in Fifteen patients (7.3%) died in hospital within 30-days due to multiorgan failure (n = 15). One- and 5-year survival was 82.7 and 72.1%, respectively  and the mean survival time was 51.6 ± 37.8 months. Overall, 30-day mortality was 7.3% (ectively .p < 0.001)  .p < 0.001) and postoperative LVEF (p < 0.001) were independent predictive factors of 30-day mortality. CPB time longer than 163 min was associated with an adverse outcome . Severity of preoperative HF, preoperative LVEF and CCT LV volumetric parameters did not play a substantial role in 30-day mortality.Hospital and 30-day mortality were identical in our series. Thirteen of the 15 patients who died in hospital underwent combined SVR and CABG surgery, six underwent combined SVR, CABG and valvular surgery, and 10 required an intra-aortic balloon pump (IABP). Univariate logistic regression revealed factors potentially predictive of 30-day mortality: long CPB time and cross-clamp time, requirement of IABP or other temporary mechanical circulatory support systems, urgent surgery, postoperative sepsis and renal failure contributed to the higher 30-day mortality rate . MultivaUnivariate logistic regression showed a potential predictive role in all-cause 5-year mortality of such factors as diabetes mellitus, peripheral artery disease, renal failure and atrial fibrillation. Preoperative MR ≥2+, preoperative LAVI, SVI, CI and postoperative LVEDVI, LVESVI and LAVI also had a potential predictive role in all-cause mortality . The mulp = 0.593) and by the univariate regression analysis .There was no difference in survival between men and women as shown by the Kaplan-Meier analysis  and LVESVI about 40.8 ± 21.5% (p < 0.001). LVEF measured in CCT increased significantly from 34.1 ± 12.1% to 43.1 ± 13.9% (p < 0.001) after SVR. The diastolic LV SI increased from 0.40 ± 0.10 to 0.52 ± 0.18 (p < 0.001); the systolic LV SI increased from 0.31 ± 0.10 to 0.36 ± 0.17 (p < 0.001).LV volumetric parameters measured in CCT in 160 patients were significantly reduced after SVR: LVEDVI decreased about 33.0 ± 17.0% (2) than in the groups with a LVESVI of 74–114 ml/m2 and ≥114 ml/m2 (p = 0.048). Five-year survival in the group with LVESVI ≤74 ml/m2 was 83.4% compared to 67.3 and 64.3% in the two other groups. An average 50 ml increase of preoperative LVESVI was associated with a 35% increase of the hazard of death (p = 0.043)  .p = 0.016), with the lowest survival rate of 60.2% in the highest tertile of postoperative LVESVI (>66.2 ml/m2) compared to the survival rates of 84.6 and 85.3% in the middle (41.6–66.2 ml/m2) and lowest (<41.6 ml/m2) teriles, respectively , and their indexed values  (2 higher than achieved LVEDVI (p = 0.00002), and anticipated LVESVI was only 2.3 ± 16.1 ml/m2 higher than achieved LVESVI (p = 0.109) (We observed a significant correlation between anticipated and effectively achieved postoperative LVEDV and LVESV ( 0.0001) . Anticip= 0.109) .Mean estimated diastolic and systolic AnV were 88.5 ± 54.2 ml and 80.5 ± 56.4 ml, respectively. The relation of the estimated AnV to the actual preoperative LVEDV and LVESV was 28.9 ± 11.3% and 37.8 ± 14.7%, respectively. This relation closely matched with the effectively postoperative achieved relation of excluded part of LV volume to the whole LV volume—LVEDV by 33.1 ± 1.6% and LVESV by 41.2 ± 21.7%.n = 60, HR 0.52, CI 0.28–0.96, p = 0.038). The Kaplan-Meier analysis showed significantly better survival in these patients compared to all other patients (p = 0.035)—group 2 and 3—with a 5-year survival rate of 84.7% (95% CI 71.3–92.1) vs. 64% (95% CI 50.8–74.6)  .p = 0.025) and a 5-year survival rate of 82.2% vs. 63.7% in all other patients (p = 0.022).Furthermore, an automated cluster analysis based on the frequency of segment involvement and its impact on survival after SVR allowed for identifying the similar scar pattern (Cluster 1) with a significantly better outcome  compared2 to 50.6 ± 18.7 ml/m2 (p < 0.001). Dividing by tertiles of preoperative LAVI revealed that patients in the lowest tertile (<49.5 ml/m2) had a lower risk of death than patients in the middle (49.5–67.6 ml/m2) and in the highest tertile (>67.6 ml/m2) of LAVI (long rank p = 0.005), with a 5-year survival in patients with LAVI <49.5 ml/m2 of 83.4% compared to the survival rate of patients in the middle and highest tertiles of 71.6 and 60.8%, respectively.LAVI decreased significantly from 60.7 ± 19.2 ml/mp < 0.001) in the whole population and from 0.79 ± 0.56 to 0.37 ± 0.44 (p < 0.001) in patients without concomitant MV surgery.MR was reduced after surgery from 1.02 ± 0.80 to 0.36 ± 0.45  provided no evidence for an effect of pre-operative diastolic SI on survival.Both systolic and diastolic SI increased significantly in all patients after SVR  due to aThis study is based on our experience of SVR performed between 2005 and 2016, since the modified Dor procedure was implemented as a standard technique in our institution.The main results of the present analysis are that both CCT-derived preoperative and postoperative LVESVI are predictive for mid-term survival. The possibility to predict the volume reduction following SVR through the separation of the aneurysm volume using a commercially available CCT evaluation software tool allows for better therapy planning and patient selection. The CCT-based analysis of local WMA provides additional information for risk assessment: aneurysms limited to seven antero-apical segments were associated with a lower risk of mortality. The follow-up analysis shows a remarkable positive improvement in NYHA class after surgery as evidence for an improvement in HF symptoms.Accurate assessment of the LV geometrical distortion, aneurysm localization and extension, and viability of the remaining myocardium is decisive for a successful SVR , 20. TheDespite excellent spatial and temporal resolution, echocardiography depends highly on exact geometric alignment, patient anatomical characteristics and the operator's skills, and it often has limitations in the visualization of the apical region. Furthermore, 2D echocardiography only allows for calculating the ventricle volume based on the empiric approximated formula, and 3D real-time volume detection is not widespread or sufficiently validated. In this study we complementarily employed echocardiography to evaluate the LV diameters, systolic function and severity of MR. The profound analysis of further echocardiographic data in the represented patient cohort, especially the prognostic role of speckle-tracking echocardiography , is presented separately .Our reasons to use CCT for SVR planning were the possibility of exact true volume detection and geometrical analysis in primarily acquired three-dimensional data sets combined with a short examination time and lack of technical restrictions even in critical patients. Previous studies , 22 demoHowever, we are well aware that CCT has clear limitations in detecting scar transmurality and viability of the remaining myocardium compared to MRI.p < 0.001) and postoperative LV EF (p < 0.001) but not the severity of preoperative HF, preoperative LV EF or CCT LV volume were independent predictive factors of 30-day mortality.In our series the overall 30-day mortality was 7.3%. Dor et al.  found hoIn our study population, 1- and 5-year actuarial survival rates were 82.7 and 72.1%, which is comparable to most published studies. A multivariate regression analysis revealed that preoperative LVEDD and LAVI as well as the patient's age, presence of diabetes mellitus and renal failure were independent significant predictive factors of all adverse outcomes .2 is essential to improve survival after surgical repair. Di Donato et al. . A postoperative LVESVI of ≥82 ml/m2 was strongly predictive of all-cause mortality, with a lowest 5-year survival rate of 49% .A CCT-based analysis of LV segmental WMA yielded additional valuable findings; it showed that the scar pattern typically involving seven antero-apical segments is associated with a better 5-year survival rate of 82.2% compared to 63.7% in all other patients with more segments involved  revealed no evidence for an effect of pre-operative diastolic SI on survival.In our series both diastolic and systolic LVSI increased immediately after surgery due to a substantial shortening of the LV long axis in relation to LV volume reduction, but it is not clear whether this effect is necessarily negative. In the follow-up study of the STICH trial, Choi et al.  also repFirst, the study is subject to the usual limitations inherent to a retrospective analysis of prospectively collected data sets. Second, CCT imaging data were not available in all patients. Third, postoperative CCT data were obtained only several days after surgery and documented the immediate effects of SVR on LV volumes and function. However, they do not reflect the effects of subsequent ventricular reverse remodeling. Fourth, CCT-based assessment of local WMA as semiquantitative detection of akinetic or dyskinetic myocardial segments involved in an aneurysm or scar formation of other localizations is dependent on the operator's skills and only offers rough scar detection. Due to the high radiation burden, we did not consider the use of CCT-based viability assessment. The CCT-based strain analysis has clear limitations because of the low temporal resolution. The analysis of systolic and diastolic LV function, myocardial dyssynergy and viability based on a two-dimensional speckle-tracking echocardiography is not included in this study. Fifth, the provided CCT-based procedure to separate the aneurysm volume using a plane determined by three landmarks on the borders of scarred to intact LV myocardium and subsequent estimation of residual volumes using the commercially available CCT volumetric tool only allows for an approximate estimation of the possible volume reduction and does not incorporate the modeling of the surgical procedure in the sense of the creation of a neoapex.The results of this study suggest that CCT-guided SVR can be performed with good mid-term survival and significant relief of HF symptoms due to LV volume reduction, reverse remodeling and functional improvement. The modified Dor procedure is an adequate surgical approach to achieve the therapeutic goals of SVR. CCT as an alternative modality to MRI can deliver relevant data for surgical planning as well as important predictive parameters for adverse outcome. The provided possibility to predict the achievable volume reduction through the separation of the aneurysm volume using a commercially available CCT volumetric tool allows for better therapy planning and patient selection.solowjowa@dhzb.de.The data analyzed in this study is subject to the following licenses/restrictions: anonymized data. Requests to access these datasets should be directed to Natalia Solowjowa, The study was performed according to the principles of the Declaration of Helsinki and approved by the ethics committee of the Charité – Universitätsmedizin Berlin (EA2/177/20). Written informed consent for surgery was obtained from all patients or their representatives.NS performed the MSCT examinations, designed the study, analyzed and interpreted the data, and wrote the manuscript. ON and YH analyzed and interpreted the data and helped writing the manuscript. AM helped design the study, analyzed and interpreted the data, and helped writing the manuscript. FH and VF performed surgery and revised the manuscript critically for important intellectual content. CK performed surgery, conceived and designed the study, analyzed and interpreted the data, and wrote the manuscript. All authors contributed to the article and approved the submitted version.This work was supported by the DZHK (German Centre for Cardiovascular Research) and the BMBF (German Ministry of Education and Research).VF disclosed financial relationships with the following entities: Medtronic GmbH, Biotronik SE & Co, Abbott GmbH & Co KG, Boston Scientific, Edwards Lifesciences, Berlin Heart, Novartis Pharma GmbH, JOTEC GmbH, and Zurich Heart. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.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.


The clinical course of COVID in the pediatric population is considered to be much milder when compared to adults; however, the occurrence of severe and fatal forms of the disease in children is non-negligible, especially in patients with comorbidities such as prematurity or cardiac disease. We report a case of a newborn with sotalol-controlled fetal ventricular tachycardia, who was postnatally diagnosed with COVID infection. The myocardial injury was sustained on the basis of pericardial effusion, left ventricular dysfunction, rapid progression to coronary artery dilation, and an arrhythmic storm. We believe that, in our case, there is a significant overlap between fetal ventricular tachycardia, associated with impaired left ventricular function, and COVID infection, diagnosed after birth; both factors contribute to the myocardial dysfunction with a fulminant clinical evolution. To our knowledge, this is the first case describing neonatal myocardial dysfunction associated with SARS-CoV infection complicating the clinical course of rare fetal tachyarrhythmia. The clinical course of COVID (caused by the severe acute respiratory syndrome coronavirus-2—SARS-CoV) in the pediatric population is much milder than in adults ,2. Data A limited number of cases of myocarditis in SARS-CoV infection in newborns are reported in the literature . We presThe patient in our case report is a female infant, born from a 39-week-pregnant woman with a history of fetal dysrhythmia, diagnosed at 33 weeks of gestation. Upon echocardiographic evaluation, the M-mode and pulsed-wave Doppler showed couplets of premature ventricular beats .During evolution, due to a decrease in contractile function, quantified by left ventricular ejection fraction and global longitudinal strain , as wellThe intrauterine evolution was favorable later on, with the maintenance of sinus rhythm and normalization of ventricular function.There was no history of symptoms, or exposure to a suspected SARS-CoV case in the mother’s family. An emergency caesarean section was performed because of the fetal distress, and a female infant with a weight of 3370 g and height of 50 cm was delivered. The newborn was hemodynamically stable, and, at that time, she did not require admission to the neonatal intensive care unit (NICU).The 12-lead electrocardiogram (ECG) performed immediately after birth revealed sinus rhythm, normal QRS voltage, QTc: 380 ms, and the first echocardiography showed normal left ventricular (LV) ejection fraction, without left and right ventricular dilation. The origins of the coronary arteries were normal.On the third day after birth, the ECG revealed sinus rhythm, but the 24-h ECG showed recurrent repetitive monomorphic VT with short periods of sinus rhythm. There was a slightly widened QRS (QRS: 85 ms) with a pattern resembling a partial left bundle branch block, and an inferior QRS axis. The ventricular rate was 220–230/min, the P waves were visible intermittently, with dissociated activity of the atria and ventricles, and with evidence of fusion and capture beats .The newborn was hemodynamically stable; however, she was transferred to the NICU. Despite propranolol treatment, sinus rhythm was not obtained, thus amiodarone was initiated for pharmacological cardioversion, initially with partial control of the VT. The second echocardiography showed minimal pericardial effusion with no clear signs of hemodynamic deterioration.On the fifth day after delivery, the diagnosis of SARS-CoV infection was confirmed for the mother and the neonate by real-time reverse transcription polymerase chain reaction (rRT-PCR) using a nasopharyngeal specimen.3/μL), elevated TnI 25.7 pg/mL , elevated D-dimer 729 ng/mL , and elevated C-reactive protein (CRP) 26.00 mg/L . Neither bacterial nor non-SARS-CoV viral infections were identified. Chest radiography showed a normal pattern of the lung tissue.Due to the clinical picture indicating myocardial injury , in addition to the usual laboratory investigations, the following were performed: chest X-rays, high-sensitivity troponin (TnI), N-terminal fraction of pro-brain natriuretic peptide (NT-proBNP), ferritin, D-dimer, and lactate measurements. The laboratory data showed a normal level of lymphocytes  with diffuse myocardial edema in the basal-anteroseptal, basal-inferoseptal, basal-inferior, mid-inferoseptal, and mid-inferior LV segments, with regional wall motion abnormalities, initially with preserved LV ejection fraction. On the twelfth day of COVID infection, the echocardiography showed LV systolic dysfunction (ejection fraction of 30%), correlated with the increased serum NT-proBNP level of 645.40 pg/mL. The 24-h ECG showed sinus tachycardia with ventricular bigeminy and trigeminy, and very frequent ventricular couplets. It was necessary to increase the dose of amiodarone to 15 μg/kg/min. The serial ECGs revealed the progression of the Q-wave amplitude in the inferior leads and nonspecific ST-T wave changes.Based on the clinical course, elevated TnI, ECG changes, and echocardiographic changes , we considered a possible inflammatory myocardial injury associated with COVID infection. Myocarditis treatment was started with intravenous immunoglobulin (2 g per kilogram) on the fifth and sixth day of the illness. In the presence of coagulopathy, low-molecular-weight heparin was initiated at a therapeutic dose. Echocardiographic evidence of coronary dilation required antiplatelet therapy. Considering the inflammatory syndrome, intravenous dexamethasone at 0.5 mg/kg/day was started on the ninth day of COVID infection. In the presence of clinical signs of heart failure and echocardiographic evidence of systolic and diastolic LV dysfunction, diuretic therapy with furosemide and spironolactone was initiated. The inotropic support with levosimendan (loading dose of 0.1 μg/kg/min) was infused on the twelfth and thirteenth day after the confirmation of COVID infection.The subsequent clinical evolution was favorable, with a substantial decrease in inflammatory biomarkers, and normalization of TnI, NT-pro-BNP, and D-dimer after 3 weeks of treatment. The repeated 24-h ECG showed sinus rhythm. The infant was discharged with LV systolic function recovery. At the time of this submission, the patient had recovered and was discharged home on oral heart failure therapy with a close follow-up.The publication of this case was approved by the institutional review board in the presence of signed informed consent obtained from the mother.To date, a number of pediatric cases of SARS-CoV infection have been reported, including neonatal infection. Amiraskari R et al. pointed out the different transmission routes for neonatal infections, including the following: vertical transmission from the mother to the fetus during pregnancy, contact between maternal blood and body fluid during a caesarean, and contact transmission of newborns in the hospital . Yang PuThe pathophysiology of this virus is still unknown. The effect of SARS-CoV infection on myocardial function is still not well established as there are no robust histological data. Cardiac complications are described in the acute phase of infection, but are more common in the post-acute phase . A possiWe report the case of a newborn with sotalol-controlled fetal VT at 33 weeks of gestation, who was diagnosed with SARS-CoV infection on the fifth day after birth. Ventricular tachycardia is a rare cause of tachycardia during fetal life and occurs in less than 2% of fetal tachyarrhythmia cases . The proSeveral studies underline the importance of IL-6 level quantification in COVID patients, as it can assess disease severity and predict the outcome ,20. Due In view of the current epidemiologic situation, SARS-CoV should be considered as a possible cause in other clinical conditions, such as myocardial inflammation, even in the absence of respiratory symptoms. Our case highlights the potential of myocardial involvement in a severe clinical course of COVID infection, mostly in infants with comorbidities.Close follow-up and repeated echocardiographic examinations are essential in detecting cardiac complications such as myocardial dysfunction and coronary artery dilation.


Wrist-hand extension function rehabilitation is a vital and difficult part of hand function recovery in spastic stroke patients. Although botulinum toxin type A (BoNTA) injection plus post injection therapy was applied to the wrist-hand rehabilitation in previous reports, conclusion was inconsistent in promoting function. For this phenomenon, proper selection of patients for BoNTA injection and correct choice of post-injection intervention could be the crucial factors for the function recovery.We reported a 46-year-old male suffered a spastic hemiplegia with wrist- hand extension deficit.Computed tomography showed cerebral hemorrhage in the left basal ganglia region.Four hundred units of BoNTA were injected into the spasticity flexors, and four-week post injection surface electromyography (sEMG) biofeedback therapy was applied to the patient.The patient exhibited post-intervention improvement in wrist-hand extensors performance , the flexors spasticity, and upper extremity function.The present case showed that 4-week of BoNTA injection plus sEMG biofeedback exercise improved the performance and function of wrist-hand extensors in the patient for short- and long-term. Proper selection of patients for BoNTA injection and correct choice of post injection exercise could play a vital role in the hand rehabilitation for patient with spastic hemiplegia. Thus, an appropriate rehabilitation treatment program is believed to be extremely important for the patients.Wrist-hand extension function recovery is a vital and difficult component in hemiplegia rehabilitation. In patients with spasticity hemiplegia, wrist-hand flexors hypertonia is prevalent which would compress function of the extensors leading to limitations on activities of daily living . BoNTA could produce transitory paralysis of the muscle through inhibition of local neuromuscular cholinergic transmission, which can relieve the disorders by spasticity. However, conclusion is inconsistent in improvement for hand function recovery through BoNTA injection plus post injection therapy in previous reports.–11 For this phenomenon, different severity of spasticity in study-population and distinct post injection rehabilitation therapy in these researches could be the key factors. Thus, BoNTA injection for the proper patient and appropriate applied of post injection rehabilitation therapy may play a vital role in the result.To manage focal spasticity of muscles, botulinum neurotoxin type A (BoNTA) injection is commonly used in patients with spastic hemiplegia.Based on this, we explored a treatment regimen of BoNTA injection plus proper post injection therapy for wrist-hand extension function recovery in proper patient with spastic hemiplegia. This case report is showing the beneficial effect of BoNTA injection plus surface electromyography (sEMG) biofeedback exercise in a mild stroke patient. In order to illustrate the research process simply, we mainly took the wrist extensors’ performance as the observing target for reflecting the extension function alteration at pre and postintervention.22.1The patient was a 46-year-old male who suddenly felt right body dysfunction on November 14, 2019, previous with risk factors for stroke . Then, he was admitted to local hospital, blood pressure was recorded as 167/105 mm Hg. Computed tomography revealed cerebral hemorrhage with a 41×52×45 mm hyperechoic mass in his left basal ganglia region. And he worked as an engineer before the stroke. After participating inpatient routine rehabilitation for 8 weeks, he was able to ambulate solely without an assistive device. After discharge, he had received instruction of home rehabilitation exercise online at home during the COVID-19 epidemic control-period. On April 15, 2020, the patient was searching for medical help for his right wrist-hand dysfunction at our outpatient rehabilitation center. Meanwhile, routine inspection showed that he had a slight extension movement  in the right wrist and fingers, which were previously in flaccid paralysis. The patient reported that he almost exclusively to perform daily activities through his left upper extremity. He could not use his right hand to drink, write, eat, and dress. After case discussion by our multi-medical team, BoNTA injections combined with biofeedback training  was recommended for the patient. And the patient responded to information about the cure arrangement. After the safety screening completed, written informed consent was signed by the patients to participate in this program.2.2Describe of time schedule of this research is shown in Figure 2.3 Four hundred units of BoNTA were injected into the belly of flexor carpi ulnaris, flexor carpi radialis, flexor digitorum profundus, flexor digitorum superficialis, flexor pollicis longus, pronator teres, palmaris longus, brachioradialis, biceps brachii, and brachialis at ten sites (Table The BoNTA injection was performed by an experienced physician (Shen Mei). The BoNTA , supplied as a vacuum-dried powder in a 100-unit vial, was reconstituted with sterile normal saline (0.9%) to reach a total volume of 2.5 ml per vial. Muscles chosen for the injection were based on previous experience of BoNTA injection for spasticity.2.4 The scale contains 15 upper-extremity functional tasks to assess movement components required for daily tasks, each item score from 0 to 5. Two sections of WMFT (time scores and function scores) could be utilized to evaluate the patient's upper limb function. In this study, we only used the functional section of the WMFT. In addition, the Modified Ashworth Scale (MAS) was utilized for evaluating the wrist-hand flexor spasticity. And the Min-Mental State Examination (MMSE) was applied to perceive any cognitive changes which may affect training or test performance in this study.Surface electromyography (sEMG) system  was utilized to monitor the active activity of the wrist-hand extensors in this study. The patient performed a continuous wrist-hand extension of isometric maximum voluntary contraction for 5 seconds after receiving the instruction by the evaluator (Wang Chao). The assessing procedures were repeated 3 times with a time interval of 30 seconds prior to the next repetition. The electromyography signals from the muscles were collected through electrodes put on the skin surface in an air-conditioned room maintained at 22 to 25°C. Then, the electromyography signals were amplified ten times and bandpass filtered from 10 to 500 Hz at a sample frequency of 1000 Hz. After signals containing noise discarded, root mean square (RMS) value, integrate electromyograph (IEGM) value, and median frequency (MF) of the power spectrum were calculated. In addition, maximum strength of the wrist-hand extensors and active range of motion (a-ROM) of the extension were also measured in this study. For assessing the upper limb function change, the Wolf Motor Function Test (WMFT) was used in this research. The WMFT scale is a global functionality evaluation of the upper limb, which is developed for people with mild to moderate stroke.2.5 Moreover, the a-ROM of the wrist-hand extension was also improved at T1 (−5°), T2 (27°), and T3 (25°) compared with T0 (−15°) , day 3 (T1), week 4 T2), and the 3-month follow-up (T3) are shown in Tables , and the3This case report aimed to illustrate the effect of BoNTA injection plus sEMG biofeedback training on wrist-hand extension function recovery through observing wrist extensors performance and function improvement in patients with spastic hemiplegia. In this study, the value of strength, a-ROM, WMFT, MAS, and sEMG signals were improved after the combined intervention compared with baseline Table . Thus, 4 Sun et al showed BoNTA injection plus modified constraint-induced movement therapy was also significantly effective in improving upper limb spasticity and function. However, it was also reported to limited evidence for improving active arm function, but improving basic upper extremity tasks  and pain.–10 Meanwhile, Rosales et al reported the same results that BoNTA injection combined rehabilitation can provide a sustained reduction in early poststroke upper extremity spasticity, but arm and hand function were not affected. Shaw et al  argued that agonist active weakness may be the critical factor rather than restriction by the spasticity. Regarding the contradiction, multi-factor may be the cause. Different severity of spasticity in study-population and distinct postinjection rehabilitation exercise may be the key influencing factors in these reports. And the optimal BoNTA dose and injection position have not reached an agreement for the affected upper limb yet, although BoNTA injection had been commonly used for the management of spasticity in stroke patients.The results of studies on BoNTA injection alone or which combined with post injection therapy for motor function recovery are inconsistent in previous literature. Pennati et al reported robotic training combined with BoNTA injection had achieved noticeable improvement in relieving spasticity and enhancing upper limb function in stroke patients.+ - 2 (MAS) which supported by previous article. Furthermore, previous studies recommended wrist-hand extensor contraction facilitating should be conducted as early as possible which is important to promote the whole hand or upper limb function recovery.,4,19 The view we hold is that exercises for the weak agonists are essential after injection of BoNTA. Otherwise, we may lose the best opportunity to achieve rehabilitation goals during “gold time” in motor function recovery.From our results, an apparent sEMG and active ROM improvements were found only 3 days after the injection, although the biofeedback motor training was not applied yet. Thus, wrist-hand extensors recruitment was indeed restricted by the spastic flexors in the patient. Regarding to dose of BoNTA and selection of proper patient, 400 units of BoNTA was injected and mild spasticity patient were chosen in our research. Based on our long-term clinical experience, 2 important points need to be paid attention to: firstly, BoNTA injection in appropriate patients who are supposed to remain the weak agonist strength for grade 2- (MMT) at least; secondly, the dose of BoNTA should be sufficient which about 400 units were recommended for antagonist spasticity of grade 2-3 (MAS) and about 300 units for the grade 1 In this study, we adopted sEMG biofeedback exercise as the post rehabilitation intervention. The sEMG biofeedback exercise is a flexible specific-task hand rehabilitation method which could train precisely on the target muscle through using sEMG for training and biofeedback. And it can be tailored for specific patient needs in isometric strengthening, motor learning, and control. In addition, previous studies exhibited that sEMG biofeedback exercise was more effective than conventional physiotherapy.,14 For this phenomenon, a probable interpretation is that sEMG biofeedback can effectively promote the accuracy of training. Thus, the sEMG biofeedback training can improve the weak agonist performance more accurately in patients with stroke spasticity, which can better improve its function.Thus, a proper post injection rehabilitation training is vital. And evidence showed BoNTA injection plus post rehabilitation achieved a more remarkable improvement compared with BoNTA injection alone.In summary, although BoNTA injection is widely used for the management of stroke spasticity in patients, the BoNTA injection combined with a sEMG biofeedback motor rehabilitation could make the patients’ benefits enlarge. Also, evaluation of proper patients for BoNTA injection should be paid attention to. Finally, a large-sample and randomized controlled trial research needs to be supplemented in the future to obtain more evidence for the conclusion.4This case report showed that 4-week of BoNTA injection plus sEMG biofeedback training significantly improved the performance and function of antagonist of the spastic-muscle for hand rehabilitation in patient with spastic hemiplegia in short- and long-term. Proper selection of patients for BoNTA injection and correct choice of post injection exercise could play a vital role in hand rehabilitation.Conceptualization: Mei Shen.Data curation: Zhang-Xiang Wu, Chao Wang.Formal analysis: Zhang-Xiang Wu, Chao Wang.Methodology: Chao Wang, Zheng Huang, Xue-han Liu.Project administration: Zhang-Xiang Wu, Chao Wang, Mei Shen.Resources: Mei Shen.Supervision: Mei Shen.Writing – original draft: Zhang-Xiang Wu, Chao Wang, Zheng Huang, Xue-han Liu, Mei Shen.Writing – review & editing: Zhang-Xiang Wu, Mei Shen.


CMR allowed for a diagnosis in 41 out of 50 (82%) patients with undetermined LVH at TTE. CMR also identified HCM in 17 out of 25 patients with apparently normal echocardiography but with ECG criteria for LVH. Finally, the reclassification of the diagnosis by CMR was associated with a change in survival risk of patients: after CMR reclassification, no events occurred in patients with undetermined or hypertensive LVH. Conclusions: CMR changed echocardiographic suspicion in almost half of patients with LVH. In the subgroup of patients with abnormal ECG, CMR identified LVH (particularly HCM) in 80% of patients. This study highlights the indication of CMR to better characterize the type, extent and severity of LVH detected at echocardiography and suspected with ECG.Background: Left ventricular hypertrophy (LVH) may be due to different causes, ranging from benign secondary forms to severe cardiomyopathies. Transthoracic Echocardiography (TTE) and ECG are the first-level examinations for LVH diagnosis. Cardiac magnetic resonance (CMR) accurately defines LVH type, extent and severity. Objectives: to evaluate the diagnostic and prognostic role of CMR in patients with TTE and/or ECG evidence of LVH. Methods: We performed CMR in 300 consecutive patients with echocardiographic and/or ECG signs of LVH. Results: Overall, 275 patients had TTE evidence of LVH, with initial suspicion of hypertrophic cardiomyopathy (HCM) in 132 (44%), cardiac amyloidosis in 41 (14%), hypertensive LVH in 48 (16%), aortic stenosis in 4 (1%), and undetermined LVH in 50 (16%). The initial echocardiographic diagnostic suspicion of LVH was confirmed in 172 patients (57.3%) and changed in 128 patients (42.7%,  The presence of left ventricular hypertrophy (LVH) is a recognized independent risk factor for cardiac-related morbidity and mortality . HoweverCMR was performed in 300 consecutive patients with suspicion of LVH, defined as the presence of at least one of the following criteria:  LVH deteStandard echocardiographic examinations of all patients were performed following the current ESC guidelines . LV hypeCardiac amyloidosis was suspected in the presence of concentric hypertrophy, ground glass appearance of ventricular myocardium on 2D echocardiography, diastolic dysfunction, thickening of interatrial septum, or global LV hypokinesia with or without apical sparring .Hypertensive LVH was defined for patients with systemic arterial hypertension (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg during office measurements), LVH with maximal end-diastolic wall thickness ≤ 14 mm, in absence of any other secondary cause of LVH .In patients with LVH, the presence of moderate–severe aortic stenosis was considered as the main cause of hypertrophy in absence of any other causes. Patients were assigned to the aortic stenosis group in the presence of moderate  or severe   cases.Athlete’s heart was defined in patients practicing intense sport training ≥2 h per day for at least 5 days per week in the last 12 months having eccentric hypertrophy, LV dilation, preserved systolic and diastolic function with normal regional wall motion .Finally, undetermined LVH was defined in cases of absence of any of the above-mentioned criteria.CMR was performed with a 1.5 Tesla scanner  with a cardiac phased array coil. Study protocol included evaluation of cardiac function with acquisition of LV ventricular short-axis cine images with the following parameters: 30 phases, slice thickness 8 mm, no gap, views per segment 8, FOV 35–40 cm, phase FOV 1, matrix 224 × 224, 45° flip angle, and a TR/TE near to 2. A set of 2-, 3- and 4-chamber cine views were also acquired.According to the Society of Cardiovascular Magnetic Resonance (SCMR) protocols, we acquired T1 mapping sequence using a Modified Look-Locker Inversion Recovery (MOLLI) method with 3(3)3(3)5 protocol.We obtained three parallel short-axis slices, including the base, midcavity, and apex of the left ventricle, at the same cardiac phase (end diastole).LGE images were acquired in short-axis and long-axis views 10 min after the administration of Gd-DTPA (dosage of 0.2 mmol/kg). The pulse sequence was an inversion recovery T1-weighted gradient-echo (GRE) sequence with the following parameters: slice thickness 8 mm, field of view 35–40 mm, reconstruction matrix 256 × 256, matrix 224 × 224, no gap between each slice, repetition time 3–5 ms, echo time 1–3, a flip angle of <25°. A TI-scout was used to choose the inversion time for myocardial nulling.Three expert investigators (III level EACVI accreditation for CMR) blinded to the clinical data performed the analysis. Quantification of the functional parameters, including LV volumes and mass, was performed using a research software package . LV volumes and mass were indexed by body surface area as previously described ,22. MaxiNative myocardial T1 was evaluated by the generation of T1 maps and the measurement of myocardial T1 performed for each myocardial segment.Combining morphological, functional and tissue findings, the differential diagnosis of LVH was performed as follows. Briefly, HCM was diagnosed in patients with asymmetrical LVH with maximal diastolic wall thickness ≥15 mm , with or without LGE. In subjects with concentric LVH, the presence of LVOT functional obstruction was considered as a proof of HCM. Cardiac amyloidosis was identified in patients with concentric LVH with the specific pattern of LGE. Hypertensive LVH was defined for patients with LVH with maximal wall thickness ≤14 mm, negative LGE and with the exclusion of any other secondary cause of LVH. In patients with LVH, the presence of moderate/severe aortic stenosis was considered as the main cause of hypertrophy in absence of LGE and any other causes. Athlete’s heart was defined in patients practicing intense sport training ≥2 h per day for at least 5 days per week in the last 12 months with eccentric hypertrophy, balanced biventricular dilation (RV EDV/LV EDV in the range 0.85–1.15), preserved systolic function with normal regional wall motion and absence of LGE. Finally, undetermined LVH was defined in cases of absence of any of the above-mentioned criteria and absence of LGE. After the echocardiographic and CMR suspicion, patients underwent further evaluations based on clinical indication to confirm the diagnosis. For instance, in the suspicion of cardiomyopathy, genetic evaluation was performed for the identification of specific pathogen mutations, and in cases of suspected cardiac amyloidosis, diphosphonate scintigraphy and umbilical fat biopsy was performed.A clinical follow-up was performed after CMR. Follow-up was performed with 3 different approaches: (1) during periodic ambulatory visitations; (2) by contacting their relatives by telephone; (3) by a general practitioner. A clinical questionnaire, compiled during the follow-up, included the following cardiac events: appropriate implantable cardioverter defibrillator (ICD) shock or antitachycardia pacing, heart failure hospitalization, sustained ventricular tachycardia on Holter electrocardiogram monitoring, resuscitated cardiac arrest and cardiac death. The appropriateness of the ICD intervention was evaluated by the referring cardiologist.t test and analysis of variance or the Wilcoxon nonparametric test were used, when appropriate, to compare continuous variables. Bonferroni correction was also used. The Kaplan–Meier curve analysis was used to compare prognosis among groups. A p value lower than 0.05 was considered statistically significant.A Kolmogorov–Smirnov test was used to test variables for normal distribution. Normally distributed variables were expressed as mean ± standard deviations (SD), whereas the median (interquartile range IQR) was used for non-normally distributed parameters. Non-normally distributed variables were logarithmically transformed for parametric analysis. Percentages were used for qualitative variables. Chi-squared test or the Fisher’s exact test were used for comparison of categorical variables, when appropriate. The ANOVA Among the 300 enrolled patients, 275 (92%) had LVH at echocardiography; 151 (50%) had ECG abnormalities ; 25 had ECG signs of LVH with negative TTE (8%).p < 0.0001) (Patients’ characteristics are summarized in  0.0001) .Among the 48 patients with TTE suspicion of hypertensive LVH, CMR excluded any other different diagnosis in eight cases (17%), whereas a CMR suggested a different diagnosis in 40: HCM in 36 cases (75%); patients typical LGE features of cardiac amyloidosis in 3 (6%); nonischemic LGE without hypertrophy in 1 , while the remaining 8 patients were reclassified as follows: 2 patients with cardiac amyloidosis (1.5%); 2 with hypertensive LVH (1.5%), 1 case with concentric hypertrophy without LGE (0.8%) with a short native myocardial T1 . Typical features of amyloidosis were absent in the remaining 19 cases: in 9 patients HCM was found (22%), 2 patients (5%) had hypertensive LVH, 2 patients (5%) had athlete’s heart, 1 patient (2%) had ischemic LGE without hypertrophy, suggesting previous myocardial infarction. Finally, in four patients (10%) LV concentric hypertrophy with negative LGE was found.Aortic stenosis was confirmed as cause of hypertrophy in three out of four patients (75%). In the remaining patient, HCM was diagnosed. The diagnosis of athlete’s heart of was confirmed in only one subject by CMR.CMR permitted us to make a diagnosis in 40 out of 49 patients (81%) with undetermined hypertrophy at echo: HCM was diagnosed in 28 patients (57%), athlete’s heart in 2 patients (4%), amyloidosis in 7 (14%), whereas LVH was excluded in 3 patients (1%).Finally, among the 25 patients with ECG criteria of LVH but with negative TTE, 5 (18%) had normal CMR. Overall, 17 of them (68%) were HCM, 2 patients (8%) had athlete’s heart and in 1 patient (4%) the cause of LVH remained undetermined. Characteristics of diagnostic groups are shown in p < 0.001). However, average maximal thickness was higher in CMR  vs. echocardiography . The higher difference was in the HCM group  and in the amyloidosis group . In 65 patients, CMR detected a MWT higher than 15 mm whereas at TTE MWT was lower. Maximal wall thickness (MWT), LVH site, LGE pattern and native T1 mapping were considered as key elements to change CMR diagnosis of LVH in respect to TTE. In general, the calculation of MWT between the two techniques correlated significantly . The LGE pattern was also useful for the final diagnosis. The typical LGE pattern of amyloidosis allowed us to identify 34 patients (97%), while in one patient a diffuse and severe increase in native T1, summed to concentric hypertrophy, allowed the diagnosis. In HCM, LGE was found in the midwall layer of hypertrophic segments in 163 patients (76%). LGE with ischemic pattern was found in one patient with LVH due to aortic stenosis. Finally, as mentioned above, in one patient with concentric hypertrophy and negative LGE, the finding of decreased native myocardial T1 suggested the diagnosis of Fabry disease, which was confirmed through genetic evaluation. TTE identified 98 out of 155 (63%) patients with septal hypertrophy at CMR, 15 out 30 (50%) with apical hypertrophy, 11 out of 28 (39%) with concentric hypertrophy and none of the two with inferior/inferolateral hypertrophy. TTE was more able to detect septal HCM than other patterns  days, and 45 major cardiac events occurred . Sudden cardiac death occurred in five patients, whereas 15 patients  died of end-stage heart failure. The Kaplan–Meier curves of In patients with LVH at echocardiography or with ECG signs of hypertrophic phenotype, CMR changed the initial echocardiographic suspicion in 42.3% cases, in particular changing the diagnosis of hypertensive LVH in 43% cases.The factors changing diagnosis were MWT measurement, the pattern of LVH. Average MWT was higher in CMR vs. echo. Tissue characterization with LGE and T1 mapping was also effective to identify HCM and cardiac amyloidosis.The final diagnosis by CMR was prognostically relevant, providing an accurate patient risk stratification in line with the type of diagnosis.The findings of the present study can be summarized in the following points: In general, this study showed that CMR allows a more accurate differentiation among the phenotypes of hypertrophy than echocardiography. This was due mainly to higher precision in the measurement of MWT, the identification of hypertrophic segments that are unlikely visualized with echocardiography, and tissue characterization by the evaluation of the presence and the pattern of myocardial fibrosis or amyloid material, defined according to LGE technique and by the T1 mapping technique. Previous studies showed that TTE can both underestimate or overestimate LV wall thickness, the first one due to poor acoustic window or focal hypertrophy, the second one due to LV trabeculation, right ventricular myocardium, papillary muscle, imaging plane obliquity apical septal bundle ,14,15. HAdditionally, CMR changed TTE diagnosis of amyloidosis in a large number of patients, that is, 56% of them. Among these, 22% of patients had a CMR diagnosis of HCM, and the others had variegated types of LVH. In this setting of patients, changes in diagnosis were due to the assessment of LGE pattern, which provides accurate information on the presence of amyloid material, in which the most common pattern is a diffuse subendocardial LGE with a noncoronary artery distribution, early darkening of the blood pool, and defects in myocardial nulling . T1 mappAdditionally, CMR provided certain diagnosis in patients with undetermined diagnosis at TTE; in this group the main CMR diagnosis was HCM, with an average difference between MWT at CMR and at TTE of 3.8 ± 2 mm. Differently, CMR confirmed TTE-diagnosis of HCM in 94% of patients. Among these, 40 had LVOT obstruction. It is noteworthy that 76% of these patients had intramyocardial LGE. Several studies have already shown that the extent and the localization of LGE is associated with wall thickness, and is an independent predictor of severe ventricular arrhythmias and sudden death ,26. FurtThe effectiveness of CMR in the diagnosis of the different types of LVH is expressed in terms of prognosis. Indeed, events did not occur in patients with a final CMR diagnosis of hypertensive LVH and in those who remained with undetermined LVH diagnosis. This reclassification of the risk of cardiac events made by CMR is consistent with the available data on the risk of cardiac events in cardiomyopathy such as amyloidosis and HCM compared to hypertensive LVH . An impoThis is a real-life study, performed without more advanced echocardiographic techniques such as speckle tracking, or 3D-echo. These more complex echocardiographic techniques could have probably improved the accuracy of the echocardiographic diagnosis, mainly in the cases of uncertain diagnosis. In this study, we showed that CMR and TTE have discrepancies in the diagnostic definition of the type of LVH, depending on several factors that include the identification of LVH of myocardial segments poorly visualized by TTE, the maximal wall thickness, and the availability of a more accurate analysis of myocardial tissue characterization with LGE. Thus, this study asks the question of whether CMR may be more frequently used in patients with evidence of LVH at TTE with the goal of a more accurate diagnostic and prognostic definition. Further studies are needed to answer this query.Clinical competency in medical knowledge: Cardiac magnetic resonance (CMR) enhances our ability to identify the causes of left ventricular hypertrophy compared to transthoracic echocardiography. After CMR, the initial diagnostic suspicion changes in >40% of cases, and this is associated with a substantial variation in the risk of cardiac events of the patients. This study highligths that CMR should be performed in every patient with echocardiographic evidence of left ventricular hypertrophy.Translational outlook: The reclassification of the risk of cardiac events of patients with left ventricular hypertrophy consequent to CMR diagnosis suggests the need to re-evalute the data on the prognostic risk associated with some cardiac conditions obtained in the pre-CMR era.


Heart failure is a clinically complex syndrome that results due to the failure of the ventricles to function as pump and oxygenate end organs. The repercussions of inadequate perfusion are seen in the form of sympathetic overactivation and third spacing, leading to clinical signs of increased blood pressure, dyspnea, fatigue, palpitations, etc. This article provided a brief overview of the clinical syndrome of heart failure; its epidemiology, risk factors, symptoms, and staging; and the mechanisms involved in disease progression. This article also described several landmark trials in heart failure that tested the efficacy of first-line drugs such as beta-blockers, angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and the latest drugs in the field of heart failure: angiotensin receptor neprilysin inhibitors. Most studies described in this article were guideline-setting trials that revolutionized the practice of medicine and cardiology. Heart failure (HF) is a complex, heterogeneous clinical syndrome that develops due to structural, functional, or physiologic abnormality of the heart, leading to a gradual and progressive failure of the ventricles to fill and to pump blood . AlthougMore recently, patients with an EF ranging from >40% and <50% have been placed into the HF with the mid-range EF (HFmEF) group . It is nDissecting the neural and hormonal components involved in HFWhen an organ undergoes stress on an acute or chronic timeline, it creates an adaptative response to maximize its function. For cardiac tissue, one of the immediate adaptative responses is the activation of the adrenergic/sympathetic nervous system (SNS), stimulating the beta-adrenergic response -10. InitThe hormonal component of the model refers to the activation of the renin-angiotensin-aldosterone system, better known as RAAS . In HFrECardiac remodeling mechanismsA significant change that a failing heart can make is cardiac myocyte hypertrophy, leading to ventricular enlargement . This prBeta-blockers and heart failureSince their invention in the late twentieth century, beta-blockers have revolutionized the practice of medicine and cardiology . The SNSToday, BBs are one of the principal drugs used in HF, combined with other first-line drugs ,15. SeveIn 1999, the Cardiac Insufficiency Bisoprolol Study II (CIBIS-II) trial, a multicenter, double-blind, randomized, placebo-controlled trial in Europe that enrolled 2,647 patients, demonstrated the advantages of bisoprolol . The stuIn 2000, Berthe et al. conducted the Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF) trial examining the effects of metoprolol . The stuThis study was pivotal in establishing BBs as one of the primary classes of drugs used in HF. At this time, it was evident that in patients with well-controlled HF, BBs demonstrated excellent efficacy in reducing mortality rates and hospitalizations secondary to HF. However, it was not clear if BBs had the same beneficial effects in patients with HF who experience severe HF symptoms and have a significantly low quality of life. The Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) study was designed to answer this question . Packer Today, BBs are almost universally used in HFrEF, in combination with other first-line HF drugs . AlthougACEIs and ARBs in heart failureACEIs and ARBs work by inhibiting the effects mediated by the RAAS pathway, through inhibiting the enzymatic activity of the angiotensin-converting enzyme (ACE) and preventing the formation of angiotensin II . HeikkilThis finding was further supported by the Studies of Left Ventricular Dysfunction (SOLVD) trial, a double-blind, randomized study conducted by Yusuf et al. . The triToday, ACEIs are established, first-line drugs in HF and are proven to reduce mortality, delay cardiac remodeling, and improve quality of life in HF patients . HoweverARBs work by physically blocking angiotensin receptors throughout the body . CurrentBecause the Losartan Heart Failure Survival (ELITE II) study concluded that ACEI use resulted in significant side effects such as cough, Granger et al. conducted the randomized, double-blind, multicenter, Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM-Alternative) trial -32. The A variant of this study was the Candesartan Cilexetil in Heart Failure Assessment of Reduction in Mortality and Morbidity (CHARM-Preserved) trial . This stThese trials laid the foundation for the use of ACEIs and ARBs in HF and are the established first-line drugs in HF. The main side effects of ACEIs include angioedema and cough, whereas ARBs can result in hypotension, dysfunction of the renal system, and hyperkalemia . Table 3Angiotensin receptor neprilysin inhibitors (ARNI) and heart failureIn 2015, the US Food and Drug Administration (FDA) approved the combined angiotensin II and neprilysin inhibitor for HF patients . NeprilyThe Angiotensin-Neprilysin Inhibition Versus Enalapril in Heart Failure (PARADIGM-HF) trial was the first study to compare ARNI and ACEIs and was conducted by Mc Murray et al. . The stuAs previously discussed, high levels of BNP correspond to pathological states such as HF. In 2019, Morrow et al. conducted the Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode (PIONEER-HF) trial to study if sacubitril/valsartan reduced N-terminal Pro-b-type natriuretic peptide (NT-Pro-BNP) levels during acute HF decompensation . The stuSimilarly, much research is needed to determine efficacious therapy in patients with HFpEF. Many studies, including the Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction , conducted by Solomon et al., demonstrated that sacubitril/valsartan did not demonstrate a reduction in cardiovascular mortality or hospitalization rates in this patient profile . Even thOther treatment modalities for HFSurgical approaches, such as heart transplants, remain one of the best options for tackling HF . AlthougThe sodium-glucose cotransporter 2 (SGLT-2) inhibitors were first marketed as anti-diabetic drugs but also have cardio-protective effects. In patients with HF and type 2 DM, the Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-Reg) trial showed that empagliflozin, an SGLT-2 inhibitor decreased cardiovascular-related mortality compared to placebo  . FurtherDevice therapyAdditionally, nonpharmacologic device therapies, such as implantable cardioverter defibrillators (ICDs), and cardiac resynchronization therapy (CRT) have also been approved by the American College of Cardiology (ACC) in the treatment of HF . PatientSymptomatic treatmentSymptomatic treatment is crucial for tackling HF since HF is a chronic condition. HF symptoms can be highly debilitating and can negatively impact the quality of life . Non-phaLimitationsAlthough neurohormonal activation is the principal driver of pathophysiology seen in HF, several other intricate mechanisms are involved in the disease progression of HF, which this article could not fully delve into. This article did not mention all the trials that were pivotal in the field of HF, and trials involving diastolic HF could not be fully explored.Heart failure is a chronic syndrome that heterogeneously affects the human body. The condition manifests in several ways depending on the cause, but common symptoms include fatigue, shortness of breath, palpitations, chest pain, etc. As evident from the review, patients with heart failure benefit from first-line drugs such as BBs, ACEIs/ARBs, and the newer ARNIs. This article has summarized some of the most prominent randomized controlled trials in the realm of heart failure and concisely presented them. We believe that this review conveys the objectives, data, and results of these trials in a digestible manner and translates this information as to how it is clinically pertinent. The clinical implications of this article revolve around understanding the data behind the landmark trials in the field of heart failure. We believe that understanding this material can allow medical professionals to communicate effectively with patients. Countless experiments and multicenter trials have demonstrated the efficacy of the first-line drugs in treating heart failure and improving the quality of life in this patient population, particularly those with reduced ejection fraction. However, approximately half of patients with heart failure are diagnosed with heart failure with preserved ejection fraction, but little is known about the efficacy of first-line drugs in this group, which calls for an urgent need for further studies in this area. Finally, there is a dire need to define, classify, and develop a universal, data-driven algorithm to treat heart failure for the best possible patient outcomes.


Atrial fibrillation is exceedingly rare in children with structurally and functionally normal hearts. We present a novel case of a 15-year-old female with known hyperthyroidism who subsequently developed atrial fibrillation. She had been suffering from fatigue, heat intolerance and myalgias for 6 months. Her initial TSH was 0.01mU/L, and free T4 was 75.4 pmol/L, with a free T3 of >30.8 pmol/L. An electrocardiogram showed atrial fibrillation with a ventricular rate of 141 beats per minute. An echocardiogram demonstrated an enlarged left atrium and ventricle, with mild mitral regurgitation. She was treated with methimazole and underwent synchronized cardioversion. She subsequently returned to a euthyroid state and remained in normal sinus rhythm. In this case, we discuss the physiologic and arrhythmogenic properties of thyroid hormone, with a summary of the existing literature on atrial fibrillation in hyperthyroidism in children. Current guidelines for treatment of atrial fibrillation are also outlined. Atrial fibrillation (AF) occurs commonly in hyperthyroidism in the adult population. However, it is a rare occurrence in children . To dateA 15-year-old female was referred to the cardiology clinic with tachycardia, murmur and known hyperthyroidism. She had been suffering from fatigue, heat intolerance and nonspecific myalgias for six months, and subsequently developed shortness of breath on exertion. Her past medical history was unremarkable and there was no known family history of AF.th percentile, +0.19 SDs) and height was 158.8 cm . Heart rate was 148 beats per minute and irregular, with a blood pressure of 138/72 mmHg. The precordium was hyperdynamic with normal first and second heart sounds, and a gallop rhythm. There was a grade II/VI systolic regurgitant murmur audible at the left lower sternal border and over the apex. Her thyroid was moderately enlarged with no palpable nodules. There was no peripheral edema or hepatosplenomegaly.On initial visit, her weight was 53.9 kg (57.6An electrocardiogram (ECG) showed AF with an average ventricular rate of 141 beats per minute, with irregular conduction and left ventricular hypertrophy , a prohormone, and triiodothyronine (T3), the active hormone . ThyroidOn the other hand, thyroid hormone has arrhythmogenic properties affecting both atria and ventricles . ElevateThe physiology behind the initiation and maintenance of paroxysmal AF is multi-factorial. Dominant theories of the pathogenesis of AF highlight electrical remodeling, structural remodeling and inflammation . HyperthHyperthyroid patients with undetectable structural heart disease have more premature supraventricular depolarizations, and non-sustained supraventricular tachycardias, as well as premature atrial complex and reduced heart rate variability . The latLone AF occurring in younger patients without underlying cardiovascular disease or comorbidities represents less than 5% of all types of AF , 25. TheThe specific management strategies for pediatric AF in general have not been well defined, but there is a need for an organized and consistent approach. Current guidelines for treatment of AF with hyperthyroidism recommend achieving a clinically euthyroid state, and most patients will spontaneously revert to sinus rhythm. Beta blockers are recommended to control the ventricular rate , 33. If Complications of AF in patients with hyperthyroidism include heart failure and thromboembolism, although it remains controversial whether AF in hyperthyroidism is associated with a higher thromboembolic risk than AF in other settings , 14, 36.The studies to date on AF in the young have required multicenter collaborations to gather reasonable numbers of patients , 43. It This particular case is demonstrative of a rare and serious complication of hyperthyroidism in a child, and we have reviewed the physiology underlying the propensity toward AF in hyperthyroidism. The general principles in the treatment of AF secondary to hyperthyroidism have also been outlined. In the adult population, it is common for clinicians to investigate for thyroid disease in patients with AF. Thus, for the general pediatric clinician, it is important to have AF and atrial arrhythmias on the differential diagnosis of complications for the hyperthyroid patient.Learning Points:-There is an important link between endocrine disorders and the cardiovascular system.-Thyroid hormone has both physiologic and arrhythmogenic properties.-Patients with clinical hyperthyroidism have an increased risk of AF.-Although rare, pediatricians should be aware of AF as a complication of hyperthyroidism in children with structurally and functionally normal hearts.DS and YW prepared the body of the manuscript. SS and SA critically reviewed the publication. 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.


Resuscitation using a percutaneous mechanical circulatory support device (iCPR) improves survival after cardiac arrest (CA). We hypothesized that the addition of inhaled nitric oxide (iNO) during iCPR might prove synergistic, leading to improved myocardial performance due to lowering of right ventricular (RV) afterload, left ventricular (LV) preload, and myocardial energetics. This study aimed to characterize the changes in LV and RV function and global myocardial work indices (GWI) following iCPR, both with and without iNO, using 2-D transesophageal echocardiography (TEE) and GWI evaluation as a novel non-invasive measurement.20 ppm, n = 5) or 0 ppm  of iNO in addition to therapeutic hypothermia for 5 h following ROSC. All animals received TEE at five pre-specified time-points and invasive hemodynamic monitoring.In 10 pigs, iCPR was initiated following electrically-induced CA and 10 min of untreated ventricular fibrillation (VF). Pigs were randomized to either 20 ppm . LV global longitudinal strain (GLS) increased in both groups following CA. LV-GLS recovered significantly better in the 20 ppm group at 5 h post-ROSC . LV-GWI decreased in both groups after CA with no difference between the groups. Within 0 ppm group, LV-GWI decreased significantly at 5 h post-ROSC compared to baseline . RV-GWI was higher in the 20 ppm group at 3 h and 5 h post-ROSC . The blood flow calculated by the Impella controller following iCPR initiation correlated well with the pulsed-wave Doppler (PWD) derived pulmonary flow .LV end-diastolic volume (LVEDV) increased significantly in both groups following CA. iCPR alone led to significant LV unloading at 5 h post-ROSC with LVEDV values reaching baseline values in both groups (iCPR after CA provided sufficient unloading and preservation of the LV systolic function by improving LV-GWI recovery. The addition of iNO to iCPR enabled better preservation of the RV-function as determined by better RV-GWI. Additionally, Impella-derived flow provided an accurate measure of total flow during iCPR. Cardiac arrest (CA) remains associated with high mortality and poor functional outcome. Despite the growing clinical use of mechanical circulatory support (MCS) for cardio-pulmonary resuscitation (CPR) after CA, the contribution towards a higher survival rate and the better functional outcome is yet to be demonstrated. An animal study showed a beneficial effect of the early use of a percutaneous mechanical circulatory support device, termed intravascular CPR (iCPR), on post-CPR survival . An addiThus, in the present study, we aimed to better understand the effect of iNO during iCPR on the myocardial performance and mechanics in a well-established large animal model of CA , 2. The The experimental protocol was approved by the appropriate governmental institution , Recklinghausen, Germany) and has been previously described , 2. All Figure Arterial blood pressure was obtained using a fluid-filled catheter  placed into the left femoral artery. For pulmonary artery pressure and cardiac output measurements, a Swan-Ganz catheter  was flow-directed into the pulmonary artery and connected to a cardiac output monitor . Impella flow was taken from the motor current based flow calculation on the AIC (Automated Impella Controller) as described in detail earlier .As described previously , 2, card2 of 1.0 without any added iNO  versus a FiO2 of 1.0 blended with 20 ppm of iNO . Therapeutic mild hypothermia was induced using 0.5L of a 6 °C cold Ringer’s solution and topical application of ice bags to the groins in all animals. The blood temperature was maintained at 33 ± 1 °C. A continuous infusion of Ringer’s solution was administered at 4 ml/kg/h to ensure adequate hydration.A 13-French sheath introducer  was placed in the right femoral artery. A modified Impella 2.5 left ventricular assist device (Abiomed) equipped with a shortened angled cannula to meet the anatomical constraints of the animal was introduced using the vascular access into the left ventricle with the help of fluoroscopy guidance, pigtail catheter  and a guidewire  , during VF and iCPR, and at 30mins, 3 h, 5 h post-ROSC. We used a commercially available ultrasound machine  equipped with a 6VT-D 3.0–8.0 MHz] TEE probe. Our detailed TEE protocol in swine has been described previously . In brie.0 MHz TERVOT x RVOT cross-sectional area x heart rate and for the LV CO = VTILVOT x LVOT cross-sectional area x heart rate.TDI was used to measure RV peak systolic tricuspid annulus velocity (TASV) from a 4-CH view as an indicator of RV longitudinal function . The PWD2-D speckle-tracking (STE) was used to define LV global longitudinal strain (LV-GLS) and RV-GLS. LV GLS was measured using the three apical chamber views ). For STE analysis of the RV the 4CH view for the RV anterior wall was used. The RV free wall was captured from a modified upper long axis view (LAX) of the RV in- and outflow tract and part of the posterior RVOT was obtained from a mid-esophageal LAX RV view . Figures were created using Graph Pad Prism version 7.0a for MAC OS X  and prepared for submission using Adobe® Illustrator® CS6 . The normal distribution of continuous variables was assessed using the Shapiro–Wilk-Test, and was expressed as mean ± standard deviation. A mixed-effects model was used for between-group comparisons at different time-points and Sidak’s test was used to account for multiple comparisons. The non-parametric Friedman-test and Dunn’s correction for multiple comparisons was used for intergroup comparisons at different time points. Pearson’s correlation test was performed to assess the correlation between the invasive thermodilution measured CO (COTD) and the PWD derived CO (COPWD). Adjusted p-values for multiple comparisons are presented and p < 0.05 was considered statistically significant.Statistical analysis was performed with STATA IC16  and Jamovi project . At least two different clear views of 4-CH, 2-CH, and LAX at all given time points were obtained in all animals.All 10 pigs survived 15 h post-ROSC and were successfully extubated. No complications due to TEE probe insertion or during TEE image acquisition were observed. Body surface area was similar between groups  .The mean heart rate at baseline was 92 ± 14 min ppm: baseline vs. iCPR: 1.4 ± 0.5 vs. 7.0 ± 0.6 mmol/L, p = 0.005; 0 ppm: Baseline vs iCPR: 1.3 ± 0.4 vs. 7.2 ± 0.6 mmol/L, p < 0.001) and returned to baseline value 3 h post-ROSC. During and after iCPR, all BGA parameters, with exception of pO2 and pCO2, did not differ between the two groups at all measured time-points. At 5 h post-ROSC, the pO2 was significantly higher in the 20 ppm group than in the 0 ppm group , and the pCO2 was significantly lower in the 20 ppm compared to the 0 ppm group .An overview of arterial blood gas analysis (BGA) throughout the experiment is provided in Fig. 0 ppm: 78.2 ± 1.1 vs. 20 ppm: 70.8 ± 1.3 mL, p < 0.001). LV-EF did not differ significantly between groups at all time points or within each group compared to baseline     . The RV-GLS values were similar between the two groups at baseline and post-ROSC. However, RV-GLS at 5 h post-ROSC was significantly lower in the 20 ppm group than 0 ppm , RV-FAC, TASV and RV-GLS, did not differ between the two groups at baseline Fig. . However20 ppm group recovered after an initial decrease and began to recover at 30 min post-ROSC to reach almost baseline values at 5 h post-ROSC  , 3 h: 896 ± 129 mmHg% (p = 0.011), and 5 h: 1,125 ± 214 mmHg% (p = 0.011); Fig. 0 ppm group  did not differ between the two groups Fig. . The LV-0 ppm vs. 20 ppm, Fig. 0 ppm group compared to the 20 ppm group . Within the 0 ppm group, the RV-GWI did not recover and remained significantly decreased at 30 min, 3 h and 5 h post-ROSC compared to baseline .At baseline, the RV myocardial work indices did not differ between groups , leading to adequate end-organ perfusion while resting the heart , 26. Pre2-consumption [The pressure-strain (PS) loop generated by tracking the global myocardial strain vs. the LVEDP/RVEDP over the cardiac cycle provides a momentary impression of the myocardial work and is comparable to the pressure–volume (PV) loops derived from conductance catheters , 11, 12.sumption , 31. Dessumption , 33.Evaluation of ventricular function is an essential component of all echocardiographic examinations. Despite the many LVEF measurement limitations, LVEF remains the most widely used parameter for systolic function evaluation . More reThe PS-loop analysis incorporates both the deformation changes and afterload, thus overcoming the limitations of load dependency . TherefoThe value and clinical implications of non-invasively estimated myocardial work indices have been tested in several clinical entities. Recently, Galli et al.  demonstrSecondary right ventricular failure can aggravate cardiogenic shock , 38. ThuThe PS-loop method may enable an accurate ventricular-arterial coupling (VAC) analysis as it overcomes some of the limitations of traditional non-invasive methods’ used to calculate the ratio of arterial to ventricular end‐systolic elastance (Ea/Ees) . The VAC3 and RV areas. 3D-TEE is believed to overcome these limitations and would have led to a more precise calculation of the derived parameters. The image quality of two-chamber-views can be limited due to swine anatomy . There are no studies comparing RV PS-loops with invasive PV-loops, to the best of our knowledge, due to lack of specific software for RV myocardial work assessment. We used the commercially available LV software provided by GE for RV myocardial work measurements. Therefore, the results must be interpreted with caution. The peripheral arterial pressure was used for PS-loop evaluation, which might be lower than the central arterial due to a lack of pressure augmentation.The small sample size of the study limits the significance of our analysis as it was not adequately powered for multiple comparisons. However, from an ethical perspective, the downsizing of experimental groups is part of the 3R strategy. The TEE measurements in swine are challenging due to specific anatomic features. Special attention was paid to avoid foreshortening of the left ventricle in echocardiography, and ante- and retroflexion of the tip was used to correctly identify the apex of the heart. Despite all the precautions, foreshortened ventricle views might have underestimated the left ventricular volumes including the stroke volume, RV DDuring resuscitation from cardiac arrest, iCPR provides sufficient unloading and preservation of end-organ perfusion by maintaining cardiac output and improving myocardial work recovery. The addition of inhaled nitric oxide enables improved preservation of RV function as determined by better recovery of RV global work indices. Myocardial work estimation by echocardiographic analysis can help understand and guide both left and right ventricular unloading to minimize myocardial stress and oxygen demand, while maintaining sufficient end-organ perfusion.