Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular mortality and morbidity. Several studies have reported that it affects the left ventricle; however, large randomized controlled trials are lacking. The current study aimed to summarize the association between OSAS and left ventricular (LV) structure and function.Electronic databases  and references were searched for articles published until March 2018. A systematic review and meta-analysis were performed to assess LV structure and function in OSAS patients based on echocardiography.p < 0.001), LV systolic diameter , and LV mass . In addition, left ventricular ejection fraction (LVEF) significantly decreased in the OSAS group compared with the controls , and the reduction in LVEF was consistent with the severity of OSAS. The OSAS group also showed an increase in left atrial diameter  and left atrial diameter volume index .In total, 17 studies with 747 OSAS patients and 426 control participants were included. Patients with OSAS showed an increase in LV diastolic diameter  contains supplementary material, which is available to authorized users. Obstructive sleep apnea syndrome (OSAS) is a common chronic disorder characterized by recurrent episodes of upper respiratory tract obstruction and hypoxia during sleep, leading to the occurrence of loud snoring, breathing interruptions, frequent awakenings or insomnia, morning fatigue, daytime sleepiness, attention deficit, and cognitive dysfunction. The diaObstructive sleep apnea syndrome is not only associated with a higher risk of occupational accidents but also leads to more cardiovascular diseases such as cardiac remodeling and dysfunction , 41. EchOwing to the overall low awareness of the relationship between OSAS and left ventricular (LV) dysfunction in clinical management, the aim of the current study was to summarize the association between OSAS and LV function and structure, in order to provide guidelines for clinical decision-making.Electronic databases including PubMed, Embase, and the Cochrane Library were searched from database inception to March 2018 using the following terms: “ventricular function, left”; “ventricular dysfunction, left”; “heart failure”; “echocardiography”; “sleep apnea, obstructive”; and “sleep-disordered breathing” (see Supplementary Table S1). In addition, we also checked the reference lists of identified reports for other potentially relevant studies. The literature search and study selection were undertaken by two reviewers independently. Any inconsistencies were settled by another researcher. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).The following criteria were used to identify potentially suitable studies: (1) articles were written fully in English; (2) enrolled participants were all adults (older than 18 years); (3) OSAS was diagnosed by polysomnography and assessed with the AHI; (4) the study included a control group; (5) the study reported at least one of the measures of LV function or structure; (6) there was no significant difference in the body mass index (BMI) of the two groups.The exclusion criteria were: (1) duplicate reports; (2) studies that had not yet terminated; (3) reviews, case reports, or animal experiments; (4) central sleep apnea; (5) OSAS patients with major comorbidities such as structural heart disease, cardiomyopathy, obstructive or restrictive lung disease demonstrated on pulmonary function testing, pulmonary hypertension, etc.; (6) previous or current treatment for OSAS; (7) studies with hypertension in OSAS group or in control group were excluded in order to avoid the definite effect of hypertension or antihypertension drugs on cardiac remodeling .m), late myocardial Doppler peak velocity (Am), LV diastolic diameter (LVEDD), LV systolic diameter (LVESD), ejection fraction (EF), isovolumetric relaxation time (IVRT), interventricular septum diameter (IWD), posterior wall diameter (PWD), LV mass (LVM), LV mass index (LVMI), left atrial diameter (LAD), left atrial diameter volume index (LAVI).Two independent readers screened and extracted data from eligible articles. The following data were extracted from the relevant studies: first author, year of publication, country, number of participants, mean age, BMI, mean AHI, OSAS diagnostic criteria, and LV morphology and function parameters. The main echocardiographic parameters included early diastolic peak flow velocity (E), late diastolic peak flow velocity (A), deceleration time of E wave (DT), early myocardial Doppler peak velocity  and reported the grouped LV function data within each stratum. The two formulae presented here were used to combine subgroups and calculate the overall means and standard deviations. However, in the subgroup analysis, each stratum was considered as a separate substudy.The equations are listed in Supplementary Table S2.2 test and the I2 statistic were applied to estimate the percentage of variability across studies due to between-study heterogeneity. Heterogeneity was considered statistically significant at p < 0.10 and I2 > 50%. The weighted mean difference (WMD) with 95% confidence intervals (CIs) was calculated using a fixed-effects model if I2 < 50% and using a random-effects model if I2 > 50%. Fisher’s z test was used to determine the statistical significance of the pooled WMDs. We conducted sensitivity analyses or subgroup analysis if I2 > 50%. Egger’s test and Begg’s test were used to examine the presence of publication bias. All analyses were performed using the statistical package Stata, version 14.0 . The quality of the enrolled studies was evaluated by two independent reviewers according to the Newcastle–Ottawa Scale ranging from 0 to 8.Cochran’s χAfter a strict screening, 739 citations were removed according to the inclusion and exclusion criteria described earlier, and a total of 17 studies with 747 OSAS patients and 426 control participants were included in the final meta-analysis  were conducted in Turkey; two studies were conducted in China, two were conducted in Spain, two were conducted in South Korea, one study was conducted in the United States, and one in Italy. In all studies, OSAS was diagnosed and assessed by polysomnography: The control group was defined as having AHI < 5 events/h, while mild, moderate, and severe OSAS were rated as, respectively, 5 ≤ AHI < 15 events/h, 15 ≤ AHI < 30 events/h, and AHI ≥ 30 events/h. For the assessment of left atrial (LA) remodeling, seven studies (41.2%) used LAD and four studies (23.5%) used LAVI. For the assessment of LV remodeling, 13 studies (76.4%) used LVEDD, 11 studies (64.7%) used LVESD, and six studies (35.3%) used LVM. For the assessment of LV function, 15 studies (88.2%) used LVEF. The main characteristics of the studies in this systematic review are listed in Table Table The parameters LVEDD, LVESD, and LVM were used to assess LV structure.p < 0.001; nonsignificant heterogeneity; Fig. p = 0.001; nonsignificant heterogeneity; Fig. Differences in LVEDD were reported in 13 studies involving 563 OSAS patients and 319 control participants. The meta-analysis showed that the LVEDD in patients with OSAS was significantly higher compared with the controls  and interleukin‑6 (IL-6) in patients with OSA . InflammThe hemodynamic changes associated with obesity might contribute to the increased LV mass observed in patients with OSA. Of interest, Parisi et al. have pointed out that HF patients with sleep disordered-breathing have higher epicardial adipose tissue (EAT) thickness values than do HF patients without nocturnal apneas , which iOverall, increased sympathetic activity, endothelial dysfunction, systemic inflammation, oxidative stress, and metabolic anomalies induced by intermittent hypoxia play major roles in the progression of LV remodeling and dysfunction.Our analysis revealed a significant increase in LA volume in patients with OSAS. Left atrial enlargement was considered to occur owing to elevated LV pressure and diastolic dysfunction. Sympathetic activation, decreased parasympathetic tone, and inflammation associated with intermittent hypoxia might contribute to atrial structural and electrical remodeling.It should be noted that recent evidence has indicated OSAS patients might be predisposed to the development and recurrence of atrial fibrillation . The forThe correlation between OSAS and right ventricular (RV) remodeling and dysfunction has also raised intense interest from researchers, but the conclusions from various have differed. Yang et al. found the inner diameters and the anterior wall thickness of the RV were increased in patients with severe OSAS and deteriorated as the disease course progressed . Vitarel2 retention stimulated central and peripheral chemoreceptors and increased sympathetic nerve activity, which induced RV dysfunction. In addition, LV dysfunction induced by OSAS may also lead to RV dysfunction, since there is a close anatomical association between the two ventricles [Several mechanisms were raised to illustrate the potential relationship between OSAS and RV changes. Prior studies suggested that permanent pulmonary hypertension was an important factor. Repetitive nocturnal arterial oxygen desaturation and hypercapnia lead to pulmonary vascular endothelium remodeling and vasoconstriction, thus increasing pulmonary artery pressure , leadingntricles .Since the effects of OSAS on the LV and RV may be different, we should conduct further analyses to uncover the precise correlation and mechanism between OSAS and RV remodeling and dysfunction.The present study was a clinical observational study. The follow-up time was not controlled. In our opinion, the duration of OSAS might be a relevant factor when assessing the effect of OSAS on cardiac structure and function, but it is very difficult to assess the duration of OSAS owing the rate of missed diagnoses in the clinic. Besides, this analysis involved no outcome data such as survival rate and risk of cardiovascular events during follow-up. Further research is needed to clarify the effect of OSAS on the long-term prognosis of patients. Additional analyses may identify the correlation and precise mechanisms between OSAS and RV remodeling.On the basis of this meta-analysis, we conclude that patients with obstructive sleep apnea syndrome (OSAS) display increased left atrial dilatation and left ventricular (LV) hypertrophy and dilatation, along with impaired LV systolic function. Therefore, more emphasis should be placed on the clinical significance of OSAS in cardiovascular risk. Treatment against OSAS such as continuous positive airway pressure can attenuate sleep apnea and might prevent the decrease in LV ejection fraction in the long term.Supplementary Table S1. Search Strategy.Supplementary Table S2. Equation.Supplementary Table S3. Quality of included studies.


While single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is a well-established noninvasive procedure for the evaluation of patients with coronary artery disease (CAD), it is unable to detect the presence of, or underestimates the extent of CAD in certain patients. We aimed to show that a bio-impedance device can detect early post-stress changes in several hemodynamic parameters, thereby serving as a potential marker for the presence of significant ischemia.Prospectively enrolled patients, referred to our Medical Center for clinically-indicated MPI, underwent testing using a Non-Invasive Cardiac System (NICaS) before and immediately after exercise. The differences between rest and stress hemodynamic parameters were compared with the severity and extent of myocardial ischemia by MPI. The study included 198 patients; mean age was 62 years, 26% were women, 54% had hypertension, and 29% diabetes mellitus. Of them, 188 patients had ≤10%, and 10 had > 10% of myocardial ischemia.p values of 0.015, 0.017, 0.040, 0.016, and < 0.001, respectively.In the first group, there was a significantly greater increase in post-exercise stroke index, stroke work index, cardiac index and cardiac power index  compared with the second group , as well as a significantly greater decrease in total peripheral resistance index (− 38.7% compared with − 16.3%), with corresponding Our data suggest that immediate post-stress changes in several hemodynamic parameters, detected by the NICaS, can be used as an important adjunct to SPECT MPI for the early detection of myocardial ischemia. Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) is a well-established noninvasive procedure for the evaluation and risk stratification of patients with coronary artery disease (CAD) . HoweverThe Non-Invasive Cardiac System  is a whole-body bio-impedance device capable of measuring various hemodynamic parameters –11. We hWe prospectively enrolled 198 patients who were referred to the Nuclear Cardiology Center at the Sheba Medical Center, Tel Hashomer, Israel, for a clinically-indicated exercise stress MPI study. Exclusion criteria included patients with: unstable angina, decompensated heart failure, systolic blood pressure > 200 mmHg or diastolic blood pressure > 110 mmHg, uncontrolled arrhythmias, severe aortic stenosis, acute pulmonary embolism, acute myocarditis or pericarditis, acute aortic dissection, intra- and extra-cardiac shunts, hemodialysis and those aged < 18 or > 80 years of age. The study was approved by the hospital’s Institutional Review Board and all patients provided written informed consent.Beta blockers and calcium-channel antagonists were terminated at least 24 h before testing, and nitrates at least 6 h before testing. During the pre-imaging stress-lab evaluation and procedures, standard 12 leads for ECG monitoring and leads for image gating were applied, and a venous catheter was inserted into an antecubital vein. The imaging room was equipped with an ECG monitor, emergency cart and oxygen source.A “stress-first-rest-second” protocol was used, as previously described –21. BrieThe QPS software computed the total perfusion deficit score by integrating the hypo-perfusion severities below normal limits in polar map coordinates . Normal The NICaS calculates the stroke volume by measuring impedance cardiography in a tetra-polar mode, derived from electrodes placed on one wrist and the contra-lateral ankle , 8. Duri2), cardiac power index (CPI=MAP*CI/451 W/m2) and total peripheral index (TPRI = MAP/CI*80 Dyn*Sec/cm5*m2).Measurements are adjusted to the body surface area to yield stroke index (SI) and cardiac index (CI). Mean arterial pressure (MAP), calculated from standard blood pressure measurements, together with SI and CI allows the calculation of stroke work index  curve was used to calculate sensitivity and specificity.Statistical analyses were performed using SPSS software . All baseline variables are described as mean ± SD. Rest, stress and changes of hemodynamic parameters are described as mean and 95% confidence interval. A one-way ANOVA was used to compare differences for continuous variables. A chi-square test was used to compare differences across subgroups for categorical variables. A 2-tailed Patient baseline clinical characteristics and medications are presented in Table p values of 0.015, 0.017, 0.040, 0.016, and < 0.001, respectively.The hemodynamic changes between rest and stress in patients with myocardial ischemia ≤10% and in those with myocardial ischemia > 10% are presented in Table Fig. Fig. While SPECT MPI is an excellent noninvasive procedure for the detection and risk stratification of patients with CAD, it may be unable to detect the presence of disease in certain patients and may underestimate its severity in others. As a result, several studies have attempted to tackle this issue using various approaches –6. In thAs already shown in multiple prior studies, the NICaS whole-body bio-impedance device is capable of reliably measuring various hemodynamic parameters –11. In tMost notably, the SI actually decreased in those patients with myocardial ischemia > 10% Table , Fig. 1.The current study certainly has some limitations. Beta-blocker therapy was discontinued at least 24 h prior to testing and no information was available regarding the use of other medications. In addition, our findings are applicable only to the present study population, comprising patients with an intermediate pretest probability for the presence of CAD without significant comorbidities. Moreover, the small number of patients with myocardial ischemia > 10% limits certainly impacts the strength of the data. Of note, the reproducibility of the measured hemodynamic parameters may be somewhat limited by the patients’ physical fitness and performance on the particular test day. Finally, it may also have been useful to have had echocardiographic data to look for valvular comorbidity and to have had additional validation of the stroke volume at rest. We intend to address these limitations in future work as well as to obtain correlation with true anatomy by coronary angiography.The results of the present study suggest that the immediate post-stress changes in several hemodynamic parameters as detected by the NICaS can be used as an important adjunct to the diagnostic approach for the early detection of myocardial ischemia. These findings can be used to improve risk assessment prior to a decision regarding the need to proceed with more complex and costly imaging modalities for the detection of myocardial ischemia. Moreover, future research should explore the potential use of the NICaS generated parameters as prognostic markers in the development and evolution of CAD.


After multivariate regression analyses, only male gender, BMI, systolic BP, creatinine, and ODI remained significantly associated with LVMI. Compared to those without LV hypertrophy (LVH), patients with LVH had higher ODI. Compared to patients with normal LV, concentric remodeling and eccentric LVH, those with concentric LVH had higher ODI. In conclusion, intermittent hypoxia was significantly associated with left ventricular remodeling; and among various parameters of intermittent hypoxia, ODI was the most relevant to LV remodeling.The present study was undertaken to examine the association between intermittent hypoxia and left ventricular (LV) remodeling and explore which parameter of intermittent hypoxia is most relevant to LV remodeling in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). Two hundred eighty six patients underwent polysomnographic examination were enrolled. Based on apnea-hypoxia index (AHI), patients were divided into no, mild, moderate and severe OSAHS groups. Between-group differences in LV remodeling and the association between parameters of intermittent hypoxia and LV remodeling was evaluated. Patients with severe OSAHS were more likely to have hypertension, and higher values of LV mass (LVM) and LVM index (LVMI). In univariate regression analysis, male, body mass index (BMI), systolic and diastolic blood pressure (BP), statins, antihypertensive drugs, creatinine, and parameters of intermittent hypoxia (AHI, obstructive apnea index [OAI], lowest oxygen saturation [LSpO With the epidemic of overweight and obesity  is a sensitive and specific marker of left ventricular remodeling  the association between intermittent hypoxia and LV remodeling; (2) which parameter of intermittent hypoxia is most relevant to LV remodeling in patients with OSAHS.Participants who were admitted to our hospital for polysomnography (PSG) examination were screened, and the exclusion criteria were as follow: (1) prior diagnosis of central sleep apnea; (2) secondary hypertension except for OSAHS-induced hypertension; (3) coexisting cardiovascular disease which could influence left ventricle structure and/or function: coronary heart disease, rheumatic heart disease, congenital heart disease, cardiomyopathy, or left ventricular ejection fraction <50%; (4) coexisting pulmonary disease: chronic obstructive pulmonary disease, acute asthma, moderate to severe pleural effusion, interstitial lung disease, or severe pulmonary infection; (5) the duration of PSG examination <7 h or poor quality of PSG images; (6) lack of important baseline clinical data. Between September 2015 and November 2017, a total of 286 people who had underwent PSG examination and qualified for the study criteria were enrolled . The sco2 was defined as obesity based on the World Health Organization criteria for Asian population , lipid panel, fasting plasma glucose (FPG) and homocysteine. Body mass index (BMI) was calculated using weight in kilograms divided by height in squared meters, and BMI ≥28 kg/m2) for more than 10 s, the apnea or hypopnea events would be recorded. Based on the the AASM Manual for the Scoring of Sleep and Associated Events Version 2.4 , oxygen desaturation index (ODI), time spent below oxygen saturation of 90% (TS90%), and mean nocturnal oxygen saturation (MSpO2) were also collected concurrently.PSG examination was performed to evaluate the apnea-hypopnea index (AHI) using Philips Respironics Alice PDx. Participants were informed about the detailed procedures of PSG examination. Twenty-four hours before PSG examination, sedative medications, alcohol, tea and coffee were not allowed. The total duration of PSG examination must be >7 h. If the airflow was completely blocked for more than 10 s or >50% reduction in respiratory airflow accompanying >3% reduction in oxygen saturation (SaO3 – (LVIDd)3]} + 0.6 g. The prevalence of obesity was high in current analysis, therefore, LVM index (LVMI) was adjusted for height2.7 and the formula was as follow: LVMI-height2.7 = LVM/height2.7 g/m2.7. LVMI-height2.7 > 49.2 g/m2.7 in men and LVMI-height2.7 > 46.7 g/m2.7 in women was defined as LVH. Based on the Ganau criteria , left ventricular internal diameter in diastole (LVIDd), left ventricular internal diameter in systole (LVIDs), interventricular septal thickness (IVS), and left ventricular posterior wall thickness (LVPW) were measured in accordance to the guideline recommendation  or median , and between-group difference was compared using one-way ANOVA for variables with normal distribution, and variables with skewed distribution were compared using Kruskal-Wallis H. Categorial variables were presented as number and percentage and between-group difference was compared using the Chi-square. Univariate regression analyses and stepwise multivariate regression analyses were performed to evaluate factors associated with LVMI-heightFrom March 2015 to November 2017, 532 patients underwent PSG examination in the cardiology department, and a total of 286 patients were included into final analysis in accordance to inclusion and exclusion criteria . Among tP < 0.05). Patients with severe OSAHS were more likely to have hypertension and to use angiotensin converting enzyme inhibitor/angiotensin receptor blocker . Serum level of uric acid was also higher in patients with severe OSAHS than those with mild or moderate OSAHS (P < 0.05). No significant differences in other baseline characteristics were observed.As presented in P < 0.05). Compared to patients without OSAHS, mild or moderate OSAHS, those with severe OSAHS had higher values of IVS, LVIDs, LVM, LVMI-height2.7, A wave velocity and e' wave velocity (P < 0.05).As presented in P < 0.05), while MSpO2 and LSpO2 was lower in patients with severe OSAHS (P < 0.05).As presented in 2, ODI, TS90%, and MSpO2 were significantly associated with LVMI-height2.7. However, after multivariate linear regression analyses, only male, BMI, systolic blood pressure, BUN, creatinine, and ODI remained significantly associated with LVMI-height2.7.As presented in P < 0.05). In addition, as presented in P < 0.05).As presented in 2.7. Second, among various parameters of intermittent hypoxia, ODI was the most relevant to LVMI-height2.7. These findings together suggest that intervention of intermittent hypoxia may help to retard LV remodeling progression and prevent LVH development. ODI may be a useful marker to predict LVH development and to reflect the efficacy of intervention for intermittent hypoxia.In the present study, we evaluated the association of intermittent hypoxia and LV remodeling in Chinese populations. There are two main findings of current study. First, intermittent hypoxia was significantly associated with left ventricular remodeling as reflected in increased LVMI-height2.7 were also significantly higher in patients with severe OSAHS. These findings together strongly indicate that presence of OSAHS is significantly associated with LV remodeling, which presented in a dose-dependent fashion. Furthermore, the velocity of A wave was faster while the lateral mitral annulus e' wave velocity was lower in patients with severe OSAHS, suggesting an impaired diastolic LV dysfunction, which we considered might be due to LV hypertrophic remodeling. With increasing prevalence and incidence of overweight and obesity, it is prudent to screen people with unrecognized or undiagnosed OSAHS, and timely and effective intervention should be implemented to prevent LV remodeling and associated cardiovascular disease.OSAHS has been considered as an important comorbidity for a variety of cardiovascular diseases . Fifth, the severity of the sample is large with 50% of patients classified as severe, as the data in this study was mainly collected from the patients suspected with OSAHS and these patients were then subjected to the PSG. Studies from Yamaguchi et al. (There are some limitations of current study needed to address. First, this is a cross-sectional study, and therefore causal relationship should not be drawn. Second, despite we have extensively adjusted for potential confounding factors, unmeasured and undetected factors might still exist and influence the association of ODI and LVMI-heighti et al.  showed tIn conclusion, the current study shows that among patients with untreated OSAHS, intermittent hypoxia is significantly associated with LV remodeling; and among various parameters of intermittent hypoxia, ODI was the most relevant to LVH. Future studies are needed to evaluate whether improvement of ODI by CPAP treatment can prevent or ameliorate LV remodeling.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 Clinical Research Ethic Committee of the Second Affiliated Hospital of NanChang University. The patients/participants provided their written informed consent to participate in this study.MD and X-sC: conception and design of the research. MD, Y-tH, and J-qX: recruiting the volunteers and performing the clinical experiments. XK and Y-fD: interpreted the results. X-sC: draft the manuscript. All authors read and approved the final manuscript.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.


To investigate the prevalence and prognostic impact of right heart failure and right ventricular-arterial uncoupling in Corona Virus Infectious Disease 2019 (COVID-19) complicated by an Acute Respiratory Distress Syndrome (ARDS).Ninety-four consecutive patients (mean age 64 years) admitted for acute respiratory failure on COVID-19 were enrolled. Coupling of right ventricular function to the pulmonary circulation was evaluated by a comprehensive trans-thoracic echocardiography with focus on the tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure (PASP) ratiop = 0.033), less often overweight or usual smokers, had lower NT-proBNP and interleukin-6, and higher arterial partial pressure of oxygen (PaO2)/fraction of inspired O2 (FIO2) ratio . In the non-survivors, PASP was increased , while TAPSE was decreased . Accordingly, the TAPSE/PASP ratio was lower than in the survivors . At univariate/multivariable analysis, the TAPSE/PASP  and PaO2/FIO2  ratios were the only independent predictors of mortality, with ROC-determined cutoff values of 159 mmHg and 0.635 mm/mmHg, respectively.The majority of patients needed ventilatory support, which was noninvasive in 22 and invasive in 37. There were 25 deaths, all in the invasively ventilated patients. Survivors were younger (62 ± 13 vs. 68 ± 12 years, 2/FIO2 in ARDS on COVID-19.COVID-19 ARDS is associated with clinically relevant uncoupling of right ventricular function from the pulmonary circulation; bedside echocardiography of TAPSE/PASP adds to the prognostic relevance of PaO Two-tailed t test for paired and unpaired data was used to assess changes between groups. Linear regression analyses and partial correlation test by Pearson’s method were used to assess univariate relations. The association between analyzed variables and outcome  was established by using Cox proportional hazard regression analyses. Univariate and multivariable linear models were used to assess potential predictors of outcome. The following variables, selected according to their potential clinical relevance, were included in the analysis: age, sex, disease duration, previous lung disease, previous coronary artery disease, cardiovascular risk factors , therapy for COVID, type of ventilation, PaO2 or invasive/noninvasive ventilation.Ninety-four patients were included in the study; they presented with fever , dyspnea , fatigue  and cough . All patients had a computed tomography (CT) scan diagnostic for diffuse or localized pneumonia. The echocardiographic assessment was performed on average 3 days after hospital admission (range 1–7 days) after the patients had been stabilized with either high flow supplemental OThe clinical data of the survivor and non-survivor patients are shown in Table 2/FIO2 lower in non-survivors. An angio CT performed when dyspnea was deemed out of proportion of standard CT imaging revealed a pulmonary embolism in nine of the patients.The patient population was globally relatively old, predominantly male and presented with pulmonary comorbidities and cardiovascular risk factors. Non-survivors were older by an average of 6 years and were more frequently smokers and overweight. The majority of the patients were anticoagulated and treated with hydroxychloroquine. A proportion of the patients also received antiviral drugs, monoclonal antibodies, and corticosteroids. Non-survivors received more frequently antiviral drugs and invasive mechanical ventilation. Serum creatinine, cardiac troponin I, C-reactive protein, interleukine-6, N-terminal pro-brain natriuretic peptide, activated partial thromboplastin time, and pro-calcitonin were higher and PaOEchocardiographic findings shown in Table A typical right heart phenotype echocardiographic examination is shown in Fig. The results of univariate and multivariable analyses are shown, respectively, in Table 2/FIO2 and TAPSE/PASP emerged as independent predictors after adjustment at multivariable analysis  , Kaplan–Meyer curves of % survival as a function of time in patients showed that patients with TAPSE/PASP or PaO2/FIO2 below ROC-derived cutoff values have reduced survival  , significantly different to those with normal levels  or only one parameter impaired . A combination of high TAPSE/PASP or PaO2/FIO2 allowed for a very high likelihood of survival. Exclusion of the 9 pulmonary embolism patients from multivariate analysis did not affect the results.Individual values for TAPSE/PASP and PaO2/FIO2 ratio in these patients.The present results show that COVID 19-induced ARDS is associated with early and pronounced uncoupling of right ventricular function from the pulmonary circulation and that its noninvasive echocardiographic assessment by the TAPSE/PASP ratio adds significantly and independently to the prognostic relevance of the PaO2/FIO2 ratio. At the moment of echocardiographic evaluation, the PaO2/FIO2 ratio had been corrected in a proportion of the survivors  to match Ea (afterload), and uncoupling expected but only in severe or rapidly evolving pulmonary hypertension . HoweverThe present results are in keeping with a recent echocardiographic study in patients with COVID-19 ARDS, in which non-survivors had a PASP at the upper limit of normal, decreased indices of RV systolic function, and longitudinal strain identified as an independent predictor of outcome , 30 unde2/FIO2 ratio, which as such is part of the definition of the syndrome [cor pulmonale in COVID-19 ARDS pathophysiology. Whether this is entirely particular to COVID-19 ARDS is uncertain as there have been no systematic evaluations of RV-PA coupling in more “typical” ARDS or other viral pneumonia ARDS controls.The most potent predictor of outcome in ARDS is the PaOsyndrome . In the 2/FIO2 ratios. Other limitations might be absence of respiratory system compliance measurements, absence of non-COVID-19 viral pneumonia controls, and exclusively noninvasive evaluations of the right heart and the pulmonary circulation. However, the results call attention to cor pulmonale as an important component of COVID-19 ARDS and plea for systematic bedside echocardiographic assessments added to blood gases and lung mechanics in the management of these patients.The present study is limited by relatively small sample size and by the small number of events. This might limit the results of the multivariate analyses and lead to a certain over-fitting. An angio-CT to diagnose acute pulmonary embolism was performed on physician in care's clinical suspicion, so that the frequency of this complication might have been under-estimated. However, PAP in the present study in the present study remained at the upper limit of normal, excluding pulmonary embolism as a cause of afterload-induced RV-PA uncoupling. Furthermore, excluding 9 of the patients with a diagnosis of pulmonary embolism did not affect the predictive capability of the TAPSE/PASP and PaOcor pulmonale” continues to be reported, albeit generally in the context of ventilatory settings associated with excessive increase in alveolar pressure and permissive hypercapnia [Approximately 4 decades ago, Zapol and Snider called attention to the pulmonary circulation and the right heart in severe ARDS . Pulmonaercapnia . The pre2/FIO2 ratio in these patients. These data call for the indispensable integration of bedside echocardiography in the assessment of COVID-19 patients in the intensive care setting.In conclusion, COVID 19-induced ARDS is associated with early and pronounced right ventricular-arterial uncoupling, and its noninvasive echocardiographic assessment by the TAPSE/PASP ratio adds significantly and independently to the prognostic relevance of the PaO


Conclusion: Systematic evaluation of sysRV is complex and should include not only volumetric parameters but also parameters of longitudinal function in addition to measurement of NT-proBNP. In patients with good image quality, 3D-echocardiography can be used to assess volumes and EF.Background: The right ventricle serves as the subaortic systemic ventricle (sysRV) in patients with congenitally corrected transposition of the great arteries (ccTGA) and in patients with transposition of the great arteries (TGA) surgically repaired by an atrial switch. SysRV can lead to late complications, primarily heart failure, significant regurgitation of the systemic atrioventricular (AV) valve, and ventricular arrhythmias with sudden cardiac death. We sought to investigate the value of 2D- and 3D-echocardiographic parameters of sysRV function. Methods: Consecutive adult patients with sysRV who presented at the adult congenital heart disease outpatient clinic were prospectively enrolled. All patients received comprehensive transthoracic echocardiography, including 3D-echocardiography, cardiac magnetic-resonance-imaging (CMR), cardiopulmonary-exercise-testing, and blood analysis for NT-proBNP. Results. A total of 27 patients were included, 18 with TGA and nine with ccTGA. Median age was 37 years , 44% were male, median NT-proBNP was 189 pg/mL ; sufficient 3D-echocardiography datasets were acquired in 78% of patients. All echocardiographic 2D and 3D volumetric function parameters correlated with CMR data, whereas a correlation was not seen with any of the longitudinal function parameters. NT-proBNP correlated with tricuspid annular plane systolic excursion (r = −0.43,  The right ventricle (RV) serves as the subaortic systemic ventricle in patients with congenitally corrected transposition of the great arteries (ccTGA) and in patients with transposition of the great arteries (TGA) surgically repaired by atrial switch. TGA occurs in 1:3100 live births and ccTGA in 1:33,000 live births ,3. AlthoAn RV in the systemic position (sysRV) can lead to late complications, primarily heart failure, significant regurgitation of the systemic atrioventricular (AV) valve, and ventricular arrhythmias with sudden cardiac death ,5,6,7. SAs a result of chronic pressure overload, RV dilatation and RV hypertrophy are present in all patients with sysRV. Transthoracic echocardiography (TTE) is the first-line diagnostic technique used for the quantification of sysRV size and function. In patients with reduced RV function, mere visual classification of the degree of dysfunction is inaccurate even if performed by expert echocardiographers . TherefoThe reference method for the assessment of RV volumetric function is cardiac magnetic resonance imaging (CMR). However, CMR is time-consuming, expensive, not universally available, cannot be used in some patients with claustrophobia and in some patients with cardiac pacemakers, particularly in those where the device was originally implanted shortly after surgery in the 1980s. True RV volumes can be measured by 3D echocardiography irrespective of the RV anatomy and geometry. A good correlation has been demonstrated between CMR-derived RVEF and 3D echocardiography-derived RVEF in several diseases, including ACHD ,12,13, bConsecutive adult patients with ccTGA or TGA surgically corrected by atrial switch who presented at the ACHD outpatient clinic between May 2017 and October 2018 were prospectively enrolled. All patients received comprehensive transthoracic echocardiography, including 3D echocardiography, CMR (unless contraindicated), cardiopulmonary exercise testing, and blood analysis for NT-proBNP.All patients provided written informed consent and the study was approved by the local ethics committee (EK #1439/2017). The study protocol conformed to the ethical guidelines of the Declaration of Helsinki.Standard transthoracic echocardiograms  were obtained from all patients using echocardiography systems equipped with 3.5 MHz transducers  Healthcare, Chicago, IL, United States). Echocardiography was performed in accordance with the recommendations of the American Society of Echocardiography and the European Association of Cardiovascular Imaging ,15. A daTwo different aspects of sysRV function are reported: (1) volumetric function parameters, i.e., 3D end-diastolic volume (EDV), 3D end-systolic volume (ESV), 3D stroke volume (SV), 3D EF, 2D monoplane EF, 2D biplane EF, and FAC; and (2) longitudinal function parameters, i.e., GLS, TAPSE, and S’ .The basal longitudinal function of the RV can be assessed by tissue Doppler imaging (S’) and by M-Mode. S’ is the peak systolic velocity of the tricuspid annulus measured by tissue Doppler imaging in an apical four-chamber view. For TAPSE, in an apical four-chamber view, the maximal systolic excursion of the lateral tricuspid annulus is measured by M-Mode. GLS of the free lateral wall of the RV was calculated by averaging the peak systolic strain of the three segments of the free lateral wall in an RV-focused four-chamber view. All 3D volumes and EF of the sysRV were analyzed both with TOMTEC 4D RV Function software  and with GE 4D Auto LVQ software .All datasets were recorded and analyzed by the same examiner (MS). Acquisition of a 3D echocardiography dataset was performed in all patients. Image quality was graded by one observer (MS) as sufficient or insufficient for analysis. Those graded sufficient were subdivided into the groups excellent, good, and moderate image quality. At the time of data analysis, the examiner was blinded to the CMR results. To assess intra-rater variability, seven randomly selected patients were analyzed a second time by the same observer. To determine inter-rater variability, seven randomly selected patients were analyzed by a second observer (MB).All CMR examinations were performed using a 1.5-Tesla Scanner  with standard protocols. In order to assess RV volumes, an axial stack of cine data was acquired using balanced steady-state free precession imaging . Trabeculations and papillary muscles were included as part of the RV volume . To dete2) and predicted maximal peak oxygen consumption (predVO2) are reported.Cardiopulmonary exercise testing (CPET) was performed to assess maximal exercise capacity. The patients were placed on an exercise bicycle to perform continuous measurements of minute ventilation, oxygen consumption, heart rate, blood pressure, and electrocardiography. Workload was increased to achieve maximal effort in 10 min. Maximal peak oxygen consumption  was analyzed from a blood sample drawn directly after completion of echocardiography according to the local laboratory’s standard procedure.t-tests were used to analyze differences among groups. CMR and 3D echocardiography measurements of sysRV volumes, EF, and SV were compared using Pearson’s correlation coefficient. The Bland–Altman analysis was performed to measure the agreement among the methods for each parameter. Intra-observer and inter-observer variabilities were determined by intra-class correlation coefficients (ICC) using a two-way random model for degree of consistency. A p-value ≤ 0.05 was considered statistically significant. SPSS Version 24  was used for all analyses.Independent sample 2 on CPET was 22 mL/kg/min , median predicted VO2 on CPET was 55.9% . At least moderate regurgitation of the systemic AV valve was present in 44% of the ccTGA patients and in 22% of the TGA patients (p = 0.049).A total of 27 patients were included in the study, 18 with TGA  and nine with ccTGA. None of the ccTGA patients had significant associated lesions such as ventricular septum defect or outflow tract obstruction. The baseline characteristics of the study cohort are summarized in The sysRV was analyzed by different parameters of volumetric and longitudinal function. GLS, FAC, TAPSE, and 2D monoplane EF were measured in all patients; S’ and 2D biplane EF were measured in 24 patients. The median value was −14% for GLS; 0.09 m/s for S’; 13 mm for TAPSE; 28% for FAC; and 39% and 41% for mono- and biplane EF by 2D Simpson method, respectively. In 2D echocardiography, there were no differences between the two groups (ccTGA and TGA) regarding volumetric function and longitudinal function parameters .A sufficient 3D dataset of the sysRV was recorded in 21 (78%) of the patients. Among these, image quality was excellent or good in nine patients (43%) and moderate in 12 patients (57%). CMR was performed in 21 of the patients. All 2D and 3D volumetric function parameters correlated with CMR data, whereas none of the longitudinal function parameters correlated with CMR data . CorrelaVolumes derived from GE’s left ventricular 3D volume software showed no correlation with CMR values.Intra-rater and inter-rater variability were analyzed by ICC for the entire cohort and for those patients with good image quality. The inter-rater variability for 3D echocardiography was 0.84 (0.08–0.97), 0.88 (0.32–0.98), 0.74 (−0.51–0.96), and 0.63 (−1.14–0.94) for EDV, ESV, EF, and SV, respectively. Intra-rater variability was 0.64 , 0.71 (0.29–0.88), 0.85 (0.64–0.94), and 0.82 (0.58–0.93) for EDV, ESV, EF, and SV, respectively, for the overall group; and 0.82 (0.21–0.96), 0.78 (0.04–0.95), 0.82 (0.22–0.96), and 0.88 (0.48–0.97) for EDV, ESV, EF, and SV, respectively, for the subgroup of patients with good image quality. The inter-rater variability for CMR was 0.86 (−0.3–0.99), 0.96 (0.86–0.99), 0.88 (−0.17–0.99), and 0.88 (−0.17–0.99) for EDV, ESV, EF, and SV, respectively.2 max did not correlate with any of the volumetric function or longitudinal function parameters. NT-proBNP correlated with CMR-EF  and TAPSE , and there was a trend toward correlation with 3D-Echo-EF  and GLS .VOTwo patients experienced major events during the study period. One ccTGA patient received a mechanical prosthetic systemic AV valve due to symptomatic severe regurgitation, and another suffered sudden cardiac death. Both were the only patients in this cohort with NT-proBNP values > 1000 .Systematic follow-up of patients with sysRV is required for the evaluation of different aspects of ventricular function. Echocardiographic examination should include assessment of both volumetric and longitudinal function. The current study shows that where adequate image quality can be obtained, 3D echocardiography is a feasible method to measure 3D volumes. Longitudinal function describes another aspect of ventricular function. NT-proBNP levels correlate with parameters of volumetric and longitudinal function.While ventricular dilatation and a reduction in EF have been reported as the regular course for patients with sysRV, which sysRV volume parameters and EF values best reflect this situation remains the subject of some discussion. In the current study, median EDV measured by CMR was 240 mL in the overall group, and median EF was 41%. The correlation between CMR and 3D echocardiography was acceptable regarding volumes and EF, while the Bland–Altman plots showed a significant bias between the two methods in the overall group. In 33% of the patient cohort, 3D echocardiography datasets could be obtained with excellent or good image quality; this included patients with a variety of EF values . If image quality was good, inter- and intra-rater variability were low. However, in the patients with inadequate image quality, inter-rater variability was high. As described in previous studies, volumes obtained by CMR were significantly higher than those obtained by echocardiography. Therefore, values measured by these two methods cannot be used interchangeably for follow-up ,13.Of the 2D volumetric parameters, FAC, monoplane EF, and biplane EF all showed a good degree of correlation with CMR-EF. It was possible to measure FAC and monoplane EF in all patients, and biplane EF was assessed in the majority of patients. Simpson’s method for volume calculation relies on geometric assumptions. This can be a significant pitfall especially when applied to the RV. Nevertheless, the method has previously been applied for RVEF calculation . A reasoCMR is expensive and contraindicated in some patients due to old pacemaker leads and systems. The current study shows that 3D echocardiography can be applied in sysRV patients, although inferior image quality can limit the reliability of this approach. We therefore suggest that 3D echocardiography be applied where good image quality can be obtained; in all other patients, biplane or monoplane volumes and EF and/or FAC should be reported.In addition to volumetric function parameters, the analysis of longitudinal function parameters has been proposed . In agre2. A possible explanation is the close range of measurements, with a median VO2 of 22 mL/min/kg , while CMR-EF showed a wide range of values (16–61%). Another explanation is that sysRV-EF as a single parameter is not sufficient to predict exercise capacity or prognosis in these patients. With a median of 189 pg/mL , NT-proBNP values were rather low despite large ventricles with reduced EF.Interestingly, none of the evaluated echocardiographic parameters correlated with VOProgressive volume overload in a failing ventricle increases diastolic wall stress and stimulates an up-regulation of systemic and local neurohumoral activation. Thus, neurohormones are commonly measured as a marker of disease progression in patients with systolic left ventricular failure . In the In light of the data reported here, we suggest the regular follow-up of patients with sysRV to assess (1) volumetric function (EDV and EF), which should be performed regularly by CMR, unless contraindicated. CMR also allows for additional baffle function assessment. In the period between CMR assessments, 3D echocardiography volumes should be obtained where image quality is excellent or good, otherwise, biplane or monoplane EF and/or FAC should be reported. (2) In addition, parameters of longitudinal function  should be obtained as these appear to provide an additional aspect of RV function. (3) Assessment of NT-proBNP levels can provide further insight into the clinical status of the patient, and it serves as an additional follow-up parameter that correlates with measures of volumetric and longitudinal function, as well as predicting mortality.This study has a number of limitations. Firstly, the data only reflect the experience of a single tertiary care center, although this also ensures the inclusion of a homogenous patient population and consistent quality of imaging. Secondly, the study population is too small to allow subgroup analysis, e.g., sex-specific aspects. However, the sample size is similar or larger than previous studies of patients with sysRV .Systematic evaluation of sysRV is complex and should include not only parameters of volumetric function but should be complemented by longitudinal function, in addition to markers of neurohumoral activation such as NT-proBNP. In patients where good image quality can be obtained, 3D echocardiography should be applied to report volumes and EF.


Objective: To assess the value of real-time three-dimensional echocardiography (RT-3DE) in evaluating changes in left atrial volume and function in type 2 diabetes mellitus (DM) and type 2 diabetic nephropathy (DN) patients.Method: 104 control subjects, 109 DN patients, and 111 DM patients were recruited and underwent RT-3DE. Data pertaining to the left atrium were analyzed using the 3DQA software in order to determine left atrial maximum volume index (LAVImax), left atrial pre-systolic volume index (LAVIp), left atrial minimum volume index (LAVImin), total left atrial ejection fraction (LAEFt), passive left atrial ejection fraction (LAEFp), and active left atrial ejection fraction (LAEFa). Differences between these three groups and correlations between individual index values and E/e' ratios were additionally assessed.Result: LAVImax, LAVIp, and LAVImin were higher in the DN and DM groups relative to controls, whereas LAEFt and LAEFp were higher in controls relative to DM and DN patients (P < 0.05). LAVImax, LAVIp, and LAVImin in the DN group were significantly higher than those in the DM group, while LAEFt, LAEFp were higher in DM patients relative to DN patients (P < 0.05). The E/e' ratio was also found to be significantly correlated with LAVImax, LAVIp, and LAVImin.Conclusion: Our results indicate that RT-3DE can be used to assess changes in left atrial volume and function in patients with diabetes and can be used to monitor disease progression-related damage to such left atrial functionality. Diabetes mellitus (DM) is a systemic metabolic disease wherein patients suffer from persistently elevated blood glucose levels as a result of impaired insulin production or sensitivity as a result of different environmental and genetic factors. DM patients typically suffer from a number of complications that can reduce the quality of life and lifespan –3. One pAbnormal diastolic functionality is an early sign of DCM development , 6. The Patients in the DM and DN groups exhibited significantly higher fasting blood glucose (FBG) and glycated hemoglobin A1C (HbA1c) values relative to control subjects (P = 0.000), whereas these values did not differ significantly between the DM and DN patient groups (P > 0.05). Patients in the DN groups exhibited significantly higher blood urea nitrogen (BUN) and creatinine (CREA) values relative to control groups and DM groups (P = 0.000), whereas these values did not differ significantly between the control groups and DM groups (P > 0.05). No significant differences were detected among the three groups with respect to systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), heart rate (HR), triglycerides (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), or low-density lipoprotein cholesterol (LDL-C) levels (P > 0.05) .We observed no significant differences in left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left atrial diameter (LAD), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), early diastolic peak velocity at the mitral valve orifice (E), late diastolic peak velocity at the mitral valve orifice (A), or late diastolic peak velocity of the mitral annulus (a') among these three participant groups (P > 0.05), whereas we did find that the average E/A value of patients in the DN group was significantly lower than that of control group patients. In addition, the average E/e' values of DN and DM group patients were significantly higher than those of control group patients, whereas e' and e'/a' values were lower than those of control group patients. Furthermore, the average E/e' value of the DN group patients was significantly elevated relative to that of DM group patients, while the e' and e'/a' values were lower than those of DM group patients (P < 0.05) .The left atrial maximum volume (LAVmax), left atrial pre-systolic volume (LAVp), and left atrial minimum volume (LAVmin) were significantly elevated in the DN and DM groups relative to the control group, whereas the total left atrial ejection fraction (LAEFt) and passive left atrial ejection fraction (LAEFp) were significantly lower in the DM and DN groups relative to the control group (P < 0.05) –3. The lE/e' was found to be significantly positively correlated with LAVImax, LAVIp, and LAVImin  .DM progression is associated with multi-system dysfunction, with cardiovascular diseases being one of the primary complications of progressive DM . DM patiIn the present study, we found that LAVImax, LAVIp, and LAVImin values in DN and DM patients were higher than those of control patients, with these values being significantly higher in DN patients relative to DM patients (P < 0.05). This suggests that left atrial volume increases in diabetic patients relative to non-diabetic controls, and that this increase is more pronounced in those with DN. We also found that LAEFt and LAEFp values were lower in DM patients relative to controls, and that these values were lower still in DN patients, suggesting that diabetic patients exhibit reductions in left atrial ejection and the conduction functionality relative to non-diabetic controls, and that this functionality is further reduced in those with DN. In addition, our results revealed that the LAEFa was elevated in DN patients relative to DM patients and controls, with no significant difference between these latter two groups. This indicates that left atrial pump functionality is enhanced in those with DN but is unchanged in those with DM relative to non-diabetic controls. This may be because left ventricular diastolic function in DN patients is impacted by both diabetes and by renal complications, further impairing left ventricular compliance and relaxation. This may in turn increase left atrial afterload such that the pump function of the left atrium is increased owing to a consequent increase in atrial contractility that is necessary to maintain left ventricular filling volume.The E/e' ratio has been validated by the American Society of Echocardiography and the European Society of Cardiovascular Imaging as a reliable index that can be used to evaluate left ventricular diastolic function and that is closely associated with left ventricular filling pressure . In the This study has a number of limitations. For one, although we grouped patients according to disease stage, we only included DM and DN patient groups, limiting our ability to resolve disease progression-related changes in RT-3DE findings. In addition, this was a single-center study with a relatively small sample size, limiting the generalizability of our findings. Future large-scale multi-center clinical studies will therefore be needed to validate and expand upon our results.In conclusion, the progression of diabetes is often associated with progressive increases in left atrial volume that are associated with impaired functionality. Our results emphasize the value of RT-3DE as an effective and efficient approach to accurately evaluating left atrial volume and function in patients with diabetes. This technology may therefore be amenable to widespread clinical application for the diagnosis and treatment of patients with DM at risk of DCM and related complications.The present study received approval from the Research Ethics Committee of the Second Affiliated Hospital of Wenzhou Medical University, and all participants provided written informed consent in accordance with the Declaration of Helsinki.From June 2019 - September 2020, we enrolled 126 newly-diagnosed DM patients and 125 patients newly diagnosed with diabetic nephropathy. The American Diabetes Association diagnostic criteria  and the All study participants underwent clinical evaluations to assess weight, height, BMI, blood pressure, medical history, and cardiovascular parameters. In addition, these participants underwent biochemical testing to measure FBG, TG, TC, HDL-C, LDL-C, HbA1c, BUN, and CREA levels.A Philips EPIQ 7C instrument equipped with an x5-1 probe at a frequency of 1-5 MHz was used for the echocardiographic examination of study participants. Initially, conventional 2D and Doppler echocardiography were conducted in order to rule out the possibility that subjects had any previously undetected structural heart diseases including cardiomyopathy, valvular disease, LV hypertrophy, or pericardial disease. A 2D ultrasound approach was used to measure LVEDD, LVESD, LAD, IVST, and LVPWT. The biplane Simpson method was used to calculate the ejection fraction (EF), while early and late diastolic velocity  at the mitral valve orifice were determined via spectrum Doppler. Early and late diastolic peak velocity  of the mitral annulus were assessed at the ventricular septum via tissue Doppler. These values were then used to compute E/A, e'/a', and E/e' ratios. Next, the 3D volume probe was utilized. Participants were instructed to hold their breath, after which images were coupled with electrocardiographic recordings. After the apical four-chamber view was clearly displayed, cine-loop clips of four consecutive cardiac cycles were continuously acquired.All the clips were collected at a > 20 frames/s framerate. RT-3DE data were analyzed with the 3DQ advanced analysis software . The lateral point, anterior point, septal point, inferior point of the mitral annulus, and the left atrial apex in the systolic and diastolic period were manually identified, while the endocardial boundary of the left atrium was identified in each frame via an automated processing method with manual adjustment as necessary. The pulmonary vein mouth and left atrial appendage were excluded so as to yield a 3D model and volume curve of the left atrium such that volume parameters could then be measured by an experienced echocardiologist blinded to subject grouping . MeasureSPSS v17.0  was used for statistical testing. Data are given as means ± SD, and were compared via LSD tests and one-way ANOVAs, as appropriate. In addition, Pearson correlation analyses were used to evaluate relationships between E/e' and LAVImax, LAVIp, and LAVImin. P < 0.05 was the significance threshold.


Regular physical activity is important for patients with established coronary heart disease as it favorably influences their coronary risk profile. General self-efficacy is a powerful predictor of health behavior change that involves increases in physical activity levels. Few studies have simultaneously measured physical activity and self-efficacy during early recovery after a first acute myocardial infarction (AMI).The aims of this study were to assess changes in objectively measured physical activity levels at 2 weeks (T2) and 6 weeks (T3) and self-reported cardiac self-efficacy at hospital discharge (T1) and at T2 and T3 in patients recovering from AMI.t tests and analysis of variance were used to examine differences in physical activity levels and cardiac self-efficacy scores, respectively.A repeated-measures design was used to recruit a purposive sample of patients from a single center in Jordan who were diagnosed with first AMI and who did not have access to cardiac rehabilitation. A body-worn activity monitor (activPAL) was used to objectively measure free-living physical activity levels for 7 consecutive days at two time points (T2 and T3). An Arabic version of the cardiac self-efficacy scale was administered at T1, T2, and T3. Paired A sample of 100 participants was recruited, of which 62% were male. The mean age of the sample was 54.5 ± 9.9 years. No statistically significant difference in physical activity levels was measured at 2 weeks (T2) and 6 weeks (T3). Cardiac self-efficacy scores improved significantly between T1, T2, and T3 across subscales and global cardiac self-efficacy.Participants recovering from AMI in Jordan did not increase their physical activity levels during the early recovery phase, although cardiac self-efficacy scores improved. This may be because the increase in cardiac self-efficacy was not matched by the practical skills and knowledge required to translate this positive psychological construct into behavioral change. This study provides a first step toward understanding the complex relationship between cardiac self-efficacy and physical activity in this population. The authors hope that these findings support the design of culturally appropriate interventions to increase physical activity levels in this population. Cardiovascular disease (CVD) is the most common cause of death worldwide, causing 31% of all deaths globally  live longer and experience fewer cardiovascular events . The EurRegular PA is also an important contributor to both primary and secondary cardiovascular prevention . PatientIt is important to provide self-management support to patients recovering from AMI to help them make healthy lifestyle changes such as increasing PA levels . PatientA WHO report on CVD identified that the Middle East, which has a population of over 400 million, has a lower level of PA than other parts of the world . ApproxiIn Jordan, conservative traditions, cultural norms, and beliefs regarding illness and recovery may contribute to low levels of PA among the general population . MoreoveCross-sectional surveys conducted in Europe have assessed self-reported PA levels in patients diagnosed with CHD. Data from over 15,000 participants showed that self-reported PA levels increased over time, with 20% of the sample reporting adequate levels of PA at follow-up . A more Self-report data on PA levels provide useful information about the context and types of PA but are limited because of variations in reporting and recall bias . MoreoveCardiac rehabilitation has an impact on average step count. In two studies, an increase of 40% in number of steps was reported during rehabilitation compared with nonrehabilitation days . It is nPrimary outcomes of PA considered in prior research include step count, stepping time, standing time, upright time (the sum of standing and stepping time), and sedentary time .Step count per day has traditionally been measured using a pedometer. A guide to health intervention was developed to classify PA, with individuals who take fewer than 5,000 steps per day considered to have a sedentary life and individuals who take more than 10,000 steps per day considered to be active . A previTime spent upright was assessed as 5.9 hours per day among an older healthy population in the United Kingdom  and 7.9 Sedentary time is recognized as an independent coronary risk factor . Few stuPerceived self-efficacy (SE) is an important psychological construct known to influence engagement with PA among cardiac patients. General SE is defined by Bandura as “beliefs in one's capabilities to organize and execute the course of action required to produce given attainments” , p. 3. ECardiac SE is a cardiac-specific measure of SE that reflects a person's belief in their ability to perform specific activities that form the foundation of secondary prevention such as healthy eating, maintaining physical functioning, and smoking cessation .Limited research has reported on the PA levels of patients during the early stages of recovery from AMI. The increasing burden of CVD and low levels of PA in Middle Eastern populations provide a compelling rationale for the need to measure PA levels and cardiac SE in patients recovering from AMI. Thus, this study was designed to measure free-living PA levels and self-reported cardiac SE during early post-AMI recovery  in patients with first AMI.The aims of this study were todetermine the PA levels  at T2 and T3; andmeasure self-reported cardiac SE levels at T1, T2, and T3.A repeated-measures design was used, and data were collected at three time points: hospital discharge (T1), 2 weeks after discharge (T2), and 6 weeks after discharge (T3). These time points were selected because health behaviors established during early recovery after AMI are likely to influence long-term behaviors.The study was carried out at Jordan University Hospital (JUH) in Amman, Jordan. JUH is a tertiary hospital with approximately 600 beds, including a 12-bed coronary care unit (CCU). JUH is one of four public cardiac centers in Jordan and conducts > 4,000 percutaneous coronary intervention (PCI) procedures per year. Patients from most cities in Jordan are referred based on contractual agreements with the Ministry of Health. JUH also receives private patients. This hospital holds 4.2% of the total number of hospital beds in Jordan and accounts for 4.1% of all hospital admissions . In JordThe target population was composed of all eligible patients admitted to the CCU with a clinically confirmed AMI (ST-elevation MI and non-ST-elevation MI). Participants were included in the study if they could read and understand the study information, were aged ≥ 18 years, were admitted to the CCU with a confirmed diagnosis of first AMI, and were clinically stable with an ejection fraction of > 35%. Patients with significant comorbidities that impede PA behaviors as well as patients treated by CABG were excluded. A sample of 100 participants was targeted, based on a power calculation performed in a previous study and on an assumed attrition rate of 20% .The University of Salford in the United Kingdom (HSCR14/120) and the institutional review board at JUH in Jordan (07/2015) granted ethical approval. The study was conducted according to the agreed protocol, and informed consent was sought before participation.Data were collected between March and December 2015. A clinical nurse identified and screened all potential patients using hospital records. Eligible patients were approached in the CCU and provided with the participant information sheets. Twenty-four to 48 hours later, hemodynamically stable patients were transferred to the medical cardiac unit. At this time, the researcher discussed the study with eligible, interested patients and obtained informed consent. Demographic and clinical data were collected from patient questionnaires and medical records. The activPAL3 monitor (a body-worn PA monitor) was attached to the participants in the outpatient clinic. The participants revisited the clinic 2 and 6 weeks after hospital discharge. The participants were asked to wear the activPAL3 monitor at all times  but were told it could be removed temporarily when exposed to water. A paper version of the Arabic version of the cardiac SE questionnaire was administered at T1, T2, and T3.not at all to 4 = completely confident). The internal consistency of the CSEQ is .90  for controlling symptoms and .87 for maintaining function  was used, gender applicability was changed, and the alternative response “Nonapplicable” was deleted. Face and content validity and reliability were examined, with the results showing the CSEQ as valid and reliable .The activPAL3 monitor is widely used to assess free-living PA, with previously established reliability and validity for step count, upright time, and sedentary time . Free-listickies). PA data are considered to be valid if data are available for a minimum of 3 days with at least 13 hours of measurement per day at each time point available for analysis (The activPAL3 is a lightweight (15 grams), small (53 × 35 × 7 mm), thigh-worn accelerometer-based device. It is attached to the skin at the midpoint of the anterior thigh using self-adhering, patented dual-layer hydrogels  were used to compare mean scores at two time points, and a repeated-measures analysis of variance was used to compare three or more time points. An alpha of .05 was used as the cutoff for significance.The activPAL3 data were downloaded using the manufacturer's software . Data were cleaned to remove nonwear periods . Data ren = 100) and an age range of 36–75 years .Table Findings relating to PA level, including step count, stepping time, standing time, upright time, and sedentary time, are shown in Table This was the first study to report on both self-reported cardiac SE and objectively measured free-living PA levels in patients with AMI during early recovery in Jordan. Mean global cardiac SE scores and associated subscale scores were found to increase significantly over time. However, this trend was not reflected in the objectively measured PA levels, which did not change significantly between T1 (2 weeks) and T2 (6 weeks).Cardiac SE is considered to be an important factor associated with behavioral change in patients with CVD . There aIn this study, patients with AMI who had not attended cardiac rehabilitation showed significant improvements in global, self-reported cardiac SE, and all subscales. This is consistent with one study conducted in the United States on a sample of patients with CHD that found a statistically significant improvement in general SE recorded 2 months post-AMI . HoweverIn addition, the degree of change in SE is affected by the measure that is used. In one U.S.-based study, exercise SE levels were evaluated in 133 participants attending cardiac rehabilitation programs. Results showed that this construct was at its highest at the beginning of cardiac rehabilitation, decreased significantly 6 months later, and then had leveled off at the 18-month follow-up .This was the first study to report on objectively measured PA in patients with AMI recorded during the early recovery period. No significant differences were found in any of the five PA parameters between T2 (Week 2) and T3 (Week 6). The low levels of PA found in this study support the findings of the WHO regarding the rising prevalence of CVD risk factors and the low general level of PA in Middle Eastern countries .The mean step count per day in this study was similar to the findings of other studies on patients with AMI and ACS  that shoComparing objectively measured PA levels among healthy adults, patients with AMI, and older adult populations (> 65 years old), the step count in this study was below the step count of older adults reported in a previous study , respectively. In addition, stepping time, standing time, and upright time in our sample were all below the results obtained from a sample of older, healthy adults . Moreover, sedentary time in the current study was higher than older adults and healthy adult populations (18.53 vs. 18.06 vs. 16.1 hours/day), respectively.Standing time has a dose–response association with all-cause mortality in adults, and increasing standing may alleviate the health risks of prolonged sitting . This stMost time spent by the participants with AMI was sedentary, with 77% overall mean sedentary time reported at T2 and T3. A study on the PA levels of healthy adults conducted in Jordan using a self-administered PA questionnaire provides an interesting comparison with the findings of this study , showingCardiac rehabilitation programs have been shown to increase the awareness and knowledge of patients regarding controlling CVD risk factors, improving self-management skills, and promoting PA . In thisThis study aimed to measure the changes in SE and PA in the early recovery period. In this study, SE increased but PA did not change. However, behavioral change is a complex process that is affected by many factors, including motivation, opportunity, and capability, each of which may interact and influence the process . It mighThis study was affected by several limitations. First, the research was conducted at a single center, which, although a major medical center with a countrywide catchment area, may limit the generalizability of the findings. Second, the sample was purposive, and > 50% of screened patients were ineligible because they had an ejection fraction < 35% and a previous AMI, were unable to read and write, or were treated with CABG. Moreover, 30% of the eligible patients with AMI refused to participate. A primary strength of this study is the objective measurement of a range of key PA parameters of a relatively large sample size with a high compliance rate, which has not been reported to date in this population.Participants recovering from AMI in Jordan did not increase their PA levels during the early recovery phase, although cardiac SE scores improved. This may be because the increase in cardiac SE was not matched by the practical skills and knowledge required to translate this positive psychological construct into behavioral change. This study was conducted in a setting where there is an absence of cardiac rehabilitation facilities, limited lifestyle intervention options, barriers to PA, and a widespread lack of knowledge regarding recommended PA levels. This study provides a first step to understanding this complex relationship and, in combination with further research, may be used to support the design of culturally appropriate interventions to increase PA levels in the target population. Further studies to understand the mechanism that increases cardiac SE among patients with AMI after hospitalization in Jordan are warranted. In addition, replication of this study with long-term measurements in different populations to confirm the results is recommended.


Cine DENSE (Displacement Encoding with Stimulated Echoes) MRI offers high resolution circumferential, radial, and longitudinal strain assessment. Dyssynchrony assessment using midwall circumferential strain corresponds to the predominant physiologic orientation of myofibers, and its effectiveness for cardiac resynchronization therapy (CRT) patient selection has recently been demonstrated . CurrentTo test the hypothesis that cine DENSE circumferential strain analysis most effectively distinguishes between HF patients referred for CRT (HF/CRT) versus HF patients not candidates for CRT (HF/no CRT) and normal volunteers.2, matrix = 128 × 128, slice thickness = 8 mm, flip angle = 20°, TR = 17 ms, TE = 1 ms, number of spiral interleaves = 6, fat suppression, temporal resolution = 17 ms, and displacement encoding frequency = 0.1 cycles/mm. Images were exported to a PC and analyzed using custom-developed segmentation, tissue tracking, and strain analysis methods that have been described previously [MRI and echocardiography were performed in 21 subjects separated into 3 groups as defined above: HF/CRT patients (N = 9), HF/no CRT patients (N = 8), and normal volunteers (N = 4). All MRI studies were performed on a 1.5 T system . An ECG-gated spiral cine DENSE pulse sequence was used to acquire images with displacement encoding applied in two orthogonal in-plane directions. Separate 14-heartbeat breath-hold acquisitions were used for each displacement encoding direction. Short-axis images were acquired at basal, mid-ventricular, and apical levels. Additional imaging parameters included field of view = 340 – 400 mmOf the 21 patients , 17 had a cardiomyopathy, 6 (35%) of which had an ischemic etiology. For all 252 segments, DENSE circumferential and radial peak timing correlated modestly . Patient-level circumferential timing measures for onset of circumferential contraction and peak circumferential contraction correlated closely . As shown in Figure MR cine DENSE assessment of circumferential strain timing using contraction onset and peak contraction effectively distinguished CRT candidates from HF patients not candidates for CRT and normal volunteers. The better discrimination of circumferential versus radial strain dyssynchrony measures has important implications for identifying the optimal imaging modality to identify CRT candidates.


Elevated cardiac troponin, which indicates cardiomyocyte injury, is common after acute ischemic stroke and is associated with poor functional outcome. Myocardial injury is part of a broad spectrum of cardiac complications that may occur after acute ischemic stroke. Previous studies have shown that in most patients, the underlying mechanism of stroke-associated myocardial injury may not be a concomitant acute coronary syndrome. Evidence from animal research and clinical and neuroimaging studies suggest that functional and structural alterations in the central autonomic network leading to stress-mediated neurocardiogenic injury may be a key underlying mechanism . However, the exact pathophysiological cascade remains unclear, and the diagnostic and therapeutic implications are unknown.The aim of this CORONA-IS (Cardiomyocyte injury following Acute Ischemic Stroke) study is to quantify autonomic dysfunction and to decipher downstream cardiac mechanisms leading to myocardial injury after acute ischemic stroke.In this prospective, observational, single-center cohort study, 300 patients with acute ischemic stroke, confirmed via cerebral magnetic resonance imaging (MRI) and presenting within 48 hours of symptom onset, will be recruited during in-hospital stay. On the basis of high-sensitivity cardiac troponin levels and corresponding to the fourth universal definition of myocardial infarction, 3 groups are defined . Each group will include approximately 100 patients. Study patients will receive routine diagnostic care. In addition, they will receive 3 Tesla cardiovascular MRI and transthoracic echocardiography within 5 days of symptom onset to provide myocardial tissue characterization and assess cardiac function, 20-min high-resolution electrocardiogram for analysis of cardiac autonomic function, and extensive biobanking. A follow-up for cardiovascular events will be conducted 3 and 12 months after inclusion.After a 4-month pilot phase, recruitment began in April 2019. We estimate a recruitment period of approximately 3 years to include 300 patients with a complete cardiovascular MRI protocol.Stroke-associated myocardial injury is a common and relevant complication. Our study has the potential to provide a better mechanistic understanding of heart and brain interactions in the setting of acute stroke. Thus, it is essential to develop algorithms for recognizing patients at risk and to refine diagnostic and therapeutic procedures.Clinicaltrials.gov NCT03892226; https://www.clinicaltrials.gov/ct2/show/NCT03892226.DERR1-10.2196/24186 Elevated cardiac troponin (cTn), which is a sign of myocardial injury, frequently occurs in the early phase after an acute ischemic stroke (AIS) and is associated with poor functional outcome, especially increased mortality ,2. UsingThe phenomenon of acute brain injuries  leading to cardiac complications, including elevated cardiac enzymes, is known for a long time. In reference to AIS, it has recently been described as stroke-heart syndrome (SHS) -13. HoweIn the TRELAS (Troponin Elevation in Acute Ischemic Stroke) study, patients with AIS with markedly elevated cTn were significantly less likely to have a corresponding culprit lesion on coronary angiography when compared with age- and sex-matched patients with non-ST elevation acute coronary syndrome  . TogetheThe aim of the Cardiomyocyte injury following Acute Ischemic Stroke (CORONA-IS) study is to gain mechanistic insights into stroke-associated myocardial injury. We intend to provide a detailed characterization of (1) myocardial tissue; (2) myocardial, ventricular, and atrial function; and (3) associated autonomic dysfunction by using multimodal diagnostic measures.The CORONA-IS study is an investigator-initiated, prospective, observational, single-center cohort study that aims to include 300 patients with AIS. In November 2018, the Ethics Committee of the Charité-Universitätsmedizin Berlin, Germany (EA4/123/18), approved the study. All study procedures are carried out in accordance with the principles of Good Clinical Practice and the Declaration of Helsinki. The study was pre-registered under clinicaltrials.gov, NCT03892226. All patients with AIS admitted to the hospital within 48 hours of symptom onset are listed in a hospital-based registry as part of an assessment of high-sensitivity cTn (hs-cTn) development in patients with AIS. All study patients have to fulfill the study inclusion criteria listed in ability to provide informed consentage ≥18 yearsdiagnosis of acute ischemic stroke and hospital admission within 48 hours of symptom onsetvisible diffusion-weighted imaging lesion in cerebral magnetic resonance imagingrepeated measurement of high-sensitivity cardiac troponin within 24 hours of admissionpregnancy or breastfeeding2)impaired renal function persistent or permanent atrial fibrillation ST-elevation in electrocardiogram fulfilling criteria of myocardial ischemiahistory of cardiac intervention  within the last 4 weeksDepending on serial measurements of hs-cTn during the acute hospital stay  precision=13 ng/l; limit of detection=5 ng/l) and according to the fourth universal definition of MI, 3 groups are defined  [4]. We Baseline Visit section), study patients receive a baseline assessment, an additional blood draw for biobanking, 3 Tesla (3T) cardiovascular magnetic resonance imaging (CMR), transthoracic echocardiography (TTE), and a 20-min high-resolution electrocardiogram (ECG) for a comprehensive assessment of cardiac autonomic function as well as a questionnaire testing cognitive function and the perception of stress. Furthermore, 3 and 12 months after discharge, patients will be followed up via structured telephone interviews for cardiovascular events and clinical outcomes , and hospital admission within 48 hours of symptom onset are included in the study. The study is carried out at the Department of Neurology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.The baseline assessment of the study patients includes demographics, medical history, medication, and information about the current stroke . Stroke severity is classified using the National Institutes of Health Scale Score. The degree of disability is assessed using the modified Rankin Scale score. The presence of chest pain and dyspnea at admission and before the event is documented. Cognitive function and the individual perception of stress will be assessed via 2 questionnaires: Perceived Stress Scale and Montreal-Cognitive-Assessment ,24. In aPatients receive a 3T cardiovascular MRI (CMR). The examination is performed on a 3T MR scanner  using ECG for cardiac gating.steady-state free-precession cine images (SSFP) are acquired during repeated breath-holds. Data are obtained for 3 long axes  and RV  and short axes stack—after contrast media application—to cover the LV . Furthermore, after cine long axis, 3 cine short axes  are conducted, serving as a base for mapping imaging . Motion-corrected T2 mapping is conducted using a fast low-angle shot (FLASH) gradient echo sequence in a 4Ch view and 3 short axis views (SAX) as basal, medial, and apical slices. T2 maps are based on images with T2 preparation times of 0/30/55 ms, slice thickness of 6.0 mm, TR of 251.49 ms, and TE of 1.32 ms.The detailed CMR protocol is depicted in Focal fibrosis imaging (late gadolinium enhancement [LGE]) is conducted 10 min after Gadobutrol application. LGE imaging is performed using a phase-sensitive inversion recovery sequence (PSIR) in the same slice position as cine imaging  as well as full coverage of the LV in a short axis package . TI was adapted to suppress the myocard.Postcontrast imaging is performed after intravenous injection of 0.15 mmol/kg body weight Gadobutrol . T1 mapping based on the Modified look-locker inversion recovery technique (MOLLI) using a 3-3-5 pattern is performed before and 15 min after contrast media application in 4Ch view and 3 short axes with basal, medial, and apical slices (imaging parameters: TR: 281.64 ms (4Ch) and 332.67 ms (SAX), TE: 1.12 ms, slice thickness: 6.0 mm, and Generalized Autocalibrating Partial Parallel Acquisition (GRAPPA) acceleration factor: 2).Finally, for further myocardial tissue characterization, motion-corrected AG Kardiale MRT (Prof Dr J Schulz-Menger) at the Department of Cardiology, Charité Campus Buch (Berlin), for further analysis. Experienced readers (Society for Cardiovascular Magnetic Resonance level III) analyzing the MR data are blinded to the clinical data. The clinical results are provided to the study patient, and in case of pathological findings that require further diagnostics or treatment, the clinical results are provided to the patients’ treating physician.Pseudonymized CMR data are transferred to the core Lab Vivid T8 . The focus of the examination is the left and right ventricular systolic as well as diastolic function and morphology. According to the guidelines of the American Society of Echocardiography, images are acquired using standard views [recommendations for cardiac chamber quantification by echocardiography in adults as normal range , mildly abnormal , moderately abnormal (30%-40%), and severely abnormal (<30%) [Patients undergo TTE on the first day after enrollment. A second TTE for evaluating dynamic changes in cardiac function is attempted on the third to fifth day thereafter. Trained physicians and trained technicians conduct the examination using the ultrasonic device rd views . The TTEl (<30%) . Values l (<30%) . In addil (<30%) . An indebiosignal analysis (Prof Dr A Bauer) at the cardiology department of the Medical University of Innsbruck, Austria. Members of the working group analyzing the data are blinded to all clinical information.In addition to routine 12-lead ECG at admission and stroke unit monitoring, included patients receive an additional 20-min high-resolution resting ECG during the first day after enrollment using the portable medilog AR4+ device (Schiller AG). The aim is to measure specific autonomic markers periodic repolarization dynamics (PRD) and deceleration capacity (DC), reflecting sympathetic and vagal components of cardiac autonomic function in addition to standard measures of heart rate variability (HRV) in time and frequency domain -31. The The study protocol includes an additional blood examination for biobanking to allow future study of further potential mechanisms. Blood drawing takes place during the first day after enrollment and includes 2 EDTA (for both whole blood and plasma samples), 1 heparin, 1 coagulation sodium citrate, and 1 serum tube. Blood withdrawal, centrifugation, and processing will be conducted by a trained study nurse. Blood samples are transferred to the Central Biomaterial Bank Charité for management and storage. After processing, the stored samples consist of 5.7 mL of EDTA whole blood; 1.5 mL of citrate plasma; and 2 mL of EDTA plasma, heparinized plasma, and serum samples each. These samples will allow measurement of various potential biomarkers of interest. Dependent on further funding, we consider to determine biomarkers of cardiac injury and stress, proinflammatory markers, and markers of endothelial dysfunction . Furthermore, we consider exploring whether patients with signs of stroke-associated myocardial injury present distinct miRNA-pattern. Finally, the design allows future cooperation with other research groups.A follow-up regarding major cardiovascular events takes place 3 and 12 months after enrollment via telephone interview and is conducted by a trained participant of the research group. A major cardiovascular event is defined as the occurrence of transient ischemic attack and ischemic stroke, intracranial hemorrhage, MI, coronary artery bypass surgery or percutaneous coronary intervention, new atrial fibrillation, hospitalization for heart failure, and death. The functional outcome is assessed using the modified Rankin Scale. In case of death, the date of death is recorded using information from registration offices. In the case of cardiovascular events, medical records will be requested from the treating physician/institution. Furthermore, Charité records will be screened for readmission or further treatment. In case of unclear loss to follow-up, mortality status will be retrieved from the residents’ registration office.Our main hypothesis is that the development of stroke-associated myocardial injury in patients with AIS is based on a stroke-related interference in the CAN resulting in myocardial tissue alterations and dysfunction  . Using aPrimary outcome measuresFrequency of Takotsubo syndrome pattern on cardiovascular magnetic resonance imaging (CMR); consisting of wall motion abnormalities together with myocardial edema (T2 mapping) but without late gadolinium enhancementFrequency and extent of myocardial edemaFrequency of recent myocardial infarction on CMRFrequency and extent of ischemic and nonischemic myocardial fibrosis according to late gadolinium enhancement imaging and according to extracellular volume fraction on T1 mappingFrequency of left ventricular dysfunction in CMR Frequency of impaired left ventricular systolic and diastolic function in the transthoracic echocardiographySecondary outcome measuresFrequency of pathologic values of Periodic Repolarization Dynamics (PRDs) and Deceleration Capacity high perceived stress in the Perceived Stress Scale Frequency of values corresponding to Frequency of cardiovascular events after 3 and 12 monthsFunctional outcome after 3 and 12 months assessed using the modified Rankin Scale.Regarding the primary hypothesis and based on the published literature, we expect a rate of acute myocardial edema on T2 mapping in CMR in approximately 15% of patients with acute myocardial injury ,36. In tTo show a significant difference between the groups (two-sided α=.05), a sample size of 48 patients per group is required to reach a power of 80% and 89 patients per group for a power of 90%. Taking into consideration that in previous studies, due to impaired compliance or technical problems, the complete protocol of CMR could be realized only in approximately 85% of the study patients, we aim to include approximately 100-105 patients in each group.t test will be used to compare continuous data. Logistic regression analyses will be used to calculate odds ratios and 95% CI to examine the association between elevated hs-cTn levels and the presence of specific structural and functional cardiac alterations in CMR and TTE. Multiple regression analyses using backward selection will be used to identify factors associated with certain myocardial alterations or ECG findings.Group comparisons (when comparing between the 3 groups) of the primary and secondary outcome measures  will be conducted using the chi-square test for categorical variables and, in case of continuous variables, using one-way analysis of variance or Kruskal-Wallis test, as appropriate. When comparing 2 groups (group 3 vs group 1 or group 3 vs group 2), Student Screening started in January 2019. After the initial pilot phase, the first patient was enrolled in April 2019. We estimate a recruitment period of approximately 3 years to enroll 300 patients with the complete CMR protocol. At the time of submission, 107 patients had been included. The final results are expected in 2023.This prospective, observational CORONA-IS study aims to clarify the underlying pathobiology of stroke-associated myocardial injury. The observation that patients with acute, severe neurological events often develop cardiac complications is well known and has been described as SHS or brain-heart syndrome . AlthougThe first goal is to visualize downstream cardiac mechanisms using CMR and TTE. We expect stroke patients with acute myocardial injury to show a higher rate and a different pattern of myocardial edema than patients with normal cTn. More precisely, we expect a myocardial edema (in T2 mapping in CMR) with wall motion abnormalities but without LGE ,38. ThisBesides structural alterations of the myocardium, we further aim to clarify whether patients with AIS and stroke-associated myocardial injury show—especially transient—functional cardiac alterations. Cardiac dysfunctions, including wall motion abnormalities or reduced EF, are often seen in patients with ischemic stroke and other acute severe neurologic conditions ,45,46. R. PRD assesses rhythmic modulations of cardiac repolarization in the low-frequency spectral range (≤0.1 Hz) [The second aim of the study is to investigate the role of CAN in the development of stroke-associated myocardial injury. There are different ways to display the influence of CAN on the cardiovascular system. Invasive diagnostic methods with direct recording of neural activity are not feasible in clinical settings. Noninvasive methods include for instance measurement of baroreceptor sensitivity or HRV. Reduced HRV and impaired baroreceptor sensitivity are associated with higher stroke severity and worse clinical outcomes ,48. Howe≤0.1 Hz) ,50. Expe≤0.1 Hz) . PRD alo≤0.1 Hz) ,31,52. TSome limitations of the study will need to be considered. First, as the aim of CORONA-IS is to investigate patients with stroke-associated myocardial injury , it is necessary to avoid including patients with clearly coronary-mediated myocardial ischemia. Hence, patients with signs of a concomitant or recent MI  will be excluded. Second, as CMR and the assessment of autonomic ECG markers depend on a rhythmic heartbeat, patients with persistent or permanent atrial fibrillation will not be included, even though they may be prone to develop stroke-associated myocardial injury. Third, specific contraindications to undergo CMR  may lead to an underrepresentation of these patients in the study. To correct for potential selection bias in the final analysis, the screen log of the study will be analyzed at the end of data collection to assess whether the rate of excluded patients due to CMR contraindications differed among the 3 groups. Finally, considering the necessity of giving informed consent to participate in the CORONA-IS trial, patients with large infarctions and aphasia may also be underrepresented.In summary, the CORONA-IS study aims to provide a deep phenotyping of patients with stroke-associated myocardial injury by using different diagnostic tools, such as 3T CMR, TTE, specific novel autonomic ECG markers, and different blood biomarkers. The goal of this prospective, observational study is to develop a better understanding of the characteristics and the pathophysiology of stroke-associated acute myocardial injury (SHS) to identify patients at risk and improve diagnostic and therapeutic procedures.