Background. Despite ongoing treatment advancements in chronic heart failure (HF), mortality and readmission rates remain high for patients hospitalized for decompensated acute HF. These patients represent a distinct HF group, which requires emergent echocardiographic evaluation in an attempt to provide optimal and individualized acute care. The role of serial advanced echocardiographic assessment in acute HF for risk stratification and treatment guidance has not been thoroughly explored. Methods. The “Beyond Myo-HF Study” is a prospective, non-interventional cohort trial designed to enroll acutely admitted patients with symptoms and/or signs of HF. The aim of this study is to investigate whether intrahospital changes of conventional and novel echocardiographic indices of myocardial function and congestion-related markers can predict early mortality, late mortality, and HF rehospitalization. As per the protocol, all patients undergo a pair of state-of-the-art echocardiographic assessments, with a rigorous protocol including speckle tracking analysis of all cardiac chambers and myocardial work analysis for the left and right ventricle, upon admission and pre-discharge. Their laboratory profile is captured at those two time-points, and their therapeutic management is recorded. Patients will be followed-up for a median period of 12 months after enrollment. Conclusions. The “Beyond Myo-HF” study is an ongoing, prospective trial aspiring to provide deep insight into the pathophysiology of acute HF, to enlighten the reverse cardiac functional and anatomical remodeling during hospitalization, and to recognize echocardiographic patterns capable of predicting adverse outcomes during and post decompensation of acute HF. Hospitalized patients with acute heart failure (HF) represent an understudied, distinct group of patients which has mainly been characterized through registries . These pIn acute decompensated HF, intensive therapy aims to lessen intracardiac pressure and central venous congestion , which iLongitudinal strain does not integrate ventricular dyssynchrony into its quantitative output and does not account for the afterload, which is subject to considerable alterations with the intensive acute HF medical therapy particularly for the RV. Myocardial work is a non-invasively derived index of myocardial function that accounts both for ventricular dyssynchrony and afterload . AlthougAccordingly, using—among others—novel echocardiographic imaging biomarkers, this observational study aims to investigate (i) the intrahospital echocardiographic variations of diverse acute HF phenotypes as a response to acute treatment, (ii) the improvement or deterioration of all chambers’ systolic function parameters and echocardiographic markers of congestion during the acute HF episode, (iii) the association of admission or discharge echocardiographic parameters with early mortality, late mortality, and HF rehospitalization, and (iv) whether suboptimal echocardiographic improvement at discharge in response to acute HF treatment is associated with poor prognosis.The “Beyond Myo-HF Study”  is an investigator-initiated, prospective, non-interventional cohort trial involving patients with acute HF. A total of 300 consecutive patients acutely admitted to the Department of Cardiology of AHEPA University General Hospital, Thessaloniki, Greece with symptoms and/or signs of HF satisfying the inclusion criteria are enrolled in the present study. Eligibility criteria are described in Demographic characteristics and baseline medical history including a history of previous hospitalization for acute HF, primary etiology, and clinical presentation of hospitalization are recorded for all participants. Pharmacological and non-pharmacological therapeutic maneuvers during the acute phase of hospitalization, as well as medical therapy upon admission and discharge, are collected. A comprehensive transthoracic echocardiographic assessment (TTE) is performed at two different time-points during hospitalization. The first TTE is performed within 24 h from admission, and the second with 24 h pre-discharge, to capture the trajectory and net variations of all echocardiographic indices of interest. A cardiac computed tomography or cardiac magnetic resonance study will be routinely performed as required to investigate the primary HF cause for undiagnosed patients. In addition, patients’ laboratory results including complete blood count, biochemical control, inflammatory markers, coagulation mechanism control, hormonal control, N-terminal pro-B-type natriuretic peptide, and high sensitivity troponin T levels are collected upon admission and prior to discharge .Before each TTE study, heart rate and brachial blood pressure using a conventional sphygmomanometer are recorded. Additionally, height and weight of each participant are recorded and utilized to determine body mass index and body surface area in accordance with the Dubois formula . InformeIn accordance with the guideline-recommended HF definitions , HF patiAll TTE studies are performed by certified sonographers/cardiologists using high-end scanners . Electrocardiogram-triggered echocardiographic data are stored offline in a cine-loop format for analysis using proprietary software. All analysis is separately performed by an expert cardiologist, blinded to the clinical data of all participants.The size of all cardiac chambers is assessed in accordance with most current recommendations . Two-dimTwo-dimensional speckle tracking echocardiography is utilized to calculate strain measurements for all four cardiac chambers. Gain settings and imaging width are adjusted to optimize the grey scale at frame rates of 50–80 Hz. On average, three different measurements are performed, using the onset of QRS as the referent point. LV, RV, and left atrial strain measurements are performed using separate proprietary software originally developed for speckle tracking analysis of each chamber. For the calculation of right atrial strain, software originally developed for the assessment of left atrial strain is utilized. For the LV, images are acquired from the apical four-chamber, apical two-chamber, and apical long-axis view. For the left atrium, images from the apical four-chamber and apical two-chamber view are employed. For the RV and right atrium, images from apical RV-focused view and apical four-chamber view, respectively, are used. Global longitudinal strain (GLS) is derived from calculation of the average of the peak systolic longitudinal strain of all segments for each chamber.Calculation of LV myocardial work (LVMW) is performed with the use of a commercially available vendor-specific software package. To estimate myocardial work indices, LV GLS and peak systolic LV pressure measurements are integrated with the aforementioned module, as previously described . The patRV myocardial work (RVMW) indices analysis is performed by adapting proprietary software originally developed for the assessment of LVMW, as previously described . SimilarAn approximation of the RV myocardial force is derived from pulmonary pressure estimates, and changes in segment length are obtained from speckle tracking echocardiography-derived strain analysis. RV global longitudinal strain (GLS), including both RV free wall and interventricular septum, are obtained from RV-focused apical four-chamber view. Pulse-wave interrogation in the basal parasternal short-axis view is applied to define timings of pulmonary valve opening and closure, whereas timings of tricuspid valve opening and closure are obtained by direct visualization of leaflets on RV-focused apical four-chamber view. RV GLS, and PASP, and PADP measurements are synchronized by right heart valve events to generate non-invasively derived pressure–strain loops for the RV. Four separate parameters of RV function are derived from the pressure–strain loops analysis. They include (i) RV global work index , calculated from the area within the global RV pressure–strain loop, (ii) RV global constructive work , an estimate of the work contributing to myocardial shortening during systole and lengthening during isovolumic relaxation, (iii) RV global wasted work , representing the work contributing to the lengthening of the cardiac myocytes during systole and the shortening during isovolumic relaxation, and (iv) RV global work efficiency , defined as the percentage of effectively spent work by the RV myocytes and obtained by the following formula: (RVGCW/[RVGCW + RVGWW]) × 100% .t-test or the analysis of variance (ANOVA) test for continuous variables depending on the number of groups. Categorical variables will be represented by frequencies and percentages (%) and continuous variables will be summarized by mean ± standard deviation. Comparison of changes in echocardiographic indexes between admission and discharge will be performed using the paired t-test or Wilcoxon signed rank test according to the normality of distribution.Baseline clinical and echocardiographic characteristics of each group will be examined and compared using the chi-square test for categorical variables and the two-sided Student’s p value of 0.05 will be considered the significance threshold for all statistical tests. All outcomes will be reported with 95% confidence intervals. Data management and statistical analyses will be conducted using SPSS software, version 26 (IBM SPSS Statistics) and R version 3.4.4 .Univariate and multivariate logistic regression analysis and Cox regression analysis will be performed to identify independent predictors of outcome at follow-up. Only covariates that are significantly associated with the endpoint at univariate analysis will be included in multivariate models. The sensitivity and specificity of resulting echocardiographic parameters for the prediction of early mortality, late mortality, and rehospitalization will be evaluated with receiver operating characteristic curves. To assess the potential additive prognostic value of novel imaging biomarkers over baseline models, the additional increase of the chi-square value will be assessed using the likelihood ratio test. A time-to-event analysis will be performed according to the Kaplan–Meier method to assess whether groups of patients with specific echocardiographic patterns are associated with better or worse clinical prognosis. Event rates will be compared by the long-rank test. A two-tailed The “Beyond Myo-HF Study” is an ongoing, prospective cohort trial of patients hospitalized for acute HF, aiming to elucidate the intrahospital echocardiographic changes and their prognostic value. By providing a comprehensive echocardiographic assessment at admission and discharge, it seeks to evaluate the acute haemodynamic changes and the subtle alterations in myocardial function by speckle tracking echocardiography, and ultimately profile subjects not responding to intensive acute HF therapy, prone to mortal events and early HF rehospitalization.Only a few studies have described the echocardiographic changes of acute HF patients from admission to discharge ,4,6. HulBoth LV and RV potential functional recovery during hospitalization for acute HF is mainly detected by longitudinal strain of LV and RV, respectively, by applying speckle tracking echocardiography ,6. This Especially for those on inotropes in the acute HF setting, suboptimal echocardiographic improvement of the intrinsic myocardial systolic properties to therapy may indicate limited myocardial reserve for the existent afterload . In patiIn the current study, the response to acute HF therapy will be assessed, among others, by computation of non-invasive LV myocardial work parameters. Such novel indices are estimated via dedicated software by integrating speckle tracking LV GLS, blood pressure as an afterload estimate, and cardiac event timing to formulate a pressure–strain loop of the LV . AccountThe RV is a thin-walled cardiac chamber with low ventricular elastance, whose contractile properties are more susceptible to its loading environment, preload, and afterload, compared with the LV . Those cFunctional tricuspid regurgitation is a very common valvular heart disease growing in parallel with the progression of HF . SignifiSome limitations of the study should be acknowledged. Although the study is prospective, and includes a state-of-the-art, rigorous echocardiographic protocol twice during hospitalization, its single-center character necessitates the confirmation of the results from other centers to ensure their clinical validity. Additionally, the association between intrahospital echocardiographic changes and therapeutic interventions is challenging, considering that therapeutic decisions are personalized and may change on a daily basis during acute HF treatment.In conclusion, acute HF management remains an understudied subject in need of further attention. Through serial assessment of the echocardiographic profile and the introduction of novel imaging biomarkers, this study has the potential to enlighten the pathophysiology of acute HF, provide guidance to individualized management, and ultimately identify early vulnerable patients requiring escalation of therapeutic decisions and close follow-up.


Cardiovascular disease (CVD) remains a leading cause of death in people living with HIV. Myocardial fibrosis is well-described in HIV infection acquired in adulthood. We evaluate the burden of fibrosis by cardiac magnetic resonance in people with perinatal HIV infection.Individuals with perinatally acquired HIV (pnHIV) diagnosed before 10 years-old and on antiretroviral treatment for ≥ 6 months were matched with uninfected controls. Patients with significant cardiometabolic co-morbidities and pregnancy were excluded. Diffuse fibrosis was assessed by cardiac magnetic resonance (CMR). with native T1 mapping for calculation of extracellular volume fraction (ECV). Viability was assessed with late gadolinium enhancement. The normality of fibrosis was assessed using the Komogrov-Smirnov test. Fibrosis between the groups was analyzed using a Mann-Whitney U test, as the data was not normally distributed. Statistical significance was defined as a p-valve < 0.05.Fourteen adults with pnHIV group and 26 controls  were assessed. The average (± standard deviation) age in the study group was 29 (± 4.3) years-old. All pnHIV had been on ART for decades. Demographic data, CMR functional/volumetric data, and pre-contrast T1 mapping values were similar between groups. Diastolic function was normal in 50% of pnHIV patients and indeterminate in most of the remainder (42%). There was no statistically significant difference in ECV between groups; p = 0.24.Perinatally-acquired HIV was not associated with diffuse myocardial fibrosis. Early exposure to ART may be cardioprotective against development of myocardial fibrosis in patients with perinatal HIV. Despite increased life expectancy with widespread use of antiretroviral therapy (ART), cardiovascular disease (CVD) remains a leading cause of mortality in people living with human immunodeficiency virus (PLWH) , 2. CurrDespite recent advances in knowledge about risk factors and prognostication of CVD in PLWH, there are sparse data from individuals with perinatally acquired HIV (pnHIV). Child death from HIV-associated cardiomyopathy has decreased; however, recent studies have shown both transient and chronic functional and structural changes by echocardiography , 8. CardWe enrolled persons with pnHIV, who were current or former patients at the Duke University Medical Center HIV clinic and included a historical control population for comparison. Inclusion criteria included age at diagnosis of less than 10 years-old with ability to provide consent, and administration of ART for at least ≥ 6 months duration, and ability to provide consent. Exclusion criteria included inability to provide consent, tolerate CMR examination, anaphylaxis to gadolinium contrast, recent medical illness requiring hospitalization in the prior 90 days, pregnancy, breastfeeding, glomerular filtrate rate < 30 mL/min/m2, hemodialysis-dependent, and arrhythmia. The study was approved by the institutional review board at Duke University Medical Center, Pro00109701.All newly enrolled participants underwent echocardiography or prior echocardiogram imaging was reviewed if obtained within 24 months. Study participants were age-matched with historic controls, who had no history of HIV infection or maternal exposure and who had undergone a CMR exam with sufficient LGE and ECV imaging. Enrolled and control group patients had no prior history of coronary artery disease, co-morbid inflammatory disease, chronic use of steroids or anti-inflammatory medication, active cancer, chemotherapy or radiation in the past year, myocardial infarction, moderate-severe valvular disease, congenital heart disease, heart failure, non-ischemic cardiomyopathy, atrial fibrillation, or intracardiac defibrillator/pacemaker placement.CMR exams were performed on a 3T scanner  in the Duke Cardiovascular Magnetic Resonance Center. Exams included functional analysis using ECG-gated steady-state free-precession (SSFP) cine imaging. Exams also included T2-weighted imaging for assessment of myocardial edema and native T1 mapping for diffuse fibrosis. Following intravenous administration of Gadolinium-based contrast agent  late-gadolinium enhancement (LGE) images were acquired to assess for scar/fibrosis and post-contrast T1 mapping was performed to calculate extracellular volume (ECV).Post-processing of CMR data was performed using Precession, HeartIT  for function and volumetric analysis. Myocardial edema was assessed visually on T2-weighted images. T1 maps were quantitatively assessed using the inline color map provided by the scanner manufacturer . Myocardial T1 relaxation time was manually measured from the maps by carefully contouring the endocardial and epicardial borders, excluding epicardial fat and blood pool . LGE wasThe normality of fibrosis was checked using the Kolmogorov-Smirnov test. Fibrosis between the groups was analyzed using a Mann-Whitney U test as the data was not normally distributed. Statistical significance was defined as a p-valve < 0.05.Fourteen patients were included in the pnHIV group . Twenty-Echocardiographic data demonstrated normal structure and systolic function by both conventional functional assessment and subclinical myocardial strain analysis. Diastolic function was normal in 50% of the pnHIV group and indeterminate in 42%. Functional and volumetric data were similar between groups. Pre-contrast T1 mapping values were similar between groups. There was no statistically significant difference in ECV between groups; p = 0.24 .This is the first study to our knowledge to examine diffuse fibrosis in PLWH on ART, who acquired HIV perinatally. This group is of particular importance to study given three decades of HIV exposure, yet with few traditional CVD risk factors. Using historic controls to compare the prevalence of abnormal myocardial fibrosis, we found no statistically significant difference in ECV fraction between pnHIV group versus those unaffected by HIV.As a part of CMR analysis in these patients, tissue characterization is performed through myocardial T1 and T2 mapping techniques, ECV calculation, and assessment of LGE by direct visualization. LGE is the gold standard for assessment of non-viable myocardium; however, LGE may not detect diffuse fibrosis due to lack of normal myocardium in extensive disease and limitations of spatial resolution . ECV fraFibrosis in PLWH has important prognostic implications, including development of heart failure and death , 14. OutOur patient population with pnHIV is younger by decades than most published studies of PLWH who have undergone CMR to evaluate for fibrosis. Younger patients may lack traditional modifiable risk factors for early CVD, specifically dyslipidemia. In our study population, the prevalence of chronic metabolic conditions known to place patients at increased risk of CVD, such as obesity, diabetes mellitus, and hypertension, was low . In addiEarly and sustained exposure to ART is also likely to play a role in mitigating cardiac fibrosis. With pnHIV initiation of ART occurs sooner after infection than if infection acquired later life , 20. LonThere are several limitations to our study. This was a pilot study in an under-studied population that was limited in sample size. Our study may not have been sufficiently powered to detect difference in ECV, as it was difficult to recruit patients to undergo CMR examination during the COVID-19 epidemic. The patients recruited in our study are also likely to be the most compliant patients. As such, the findings may not be as generalizable to a broader context of PLWH. Our study was also a cross-sectional design, and did not prospectively follow patients longitudinally with serial CMRs to detect subtle changes in pre-contrast T1, LGE or ECV with time.No differences were detected in CMR-based markers of cardiac fibrosis among young adults with pnHIV and controls. Future direction should include serial assessment of tissue characterization over time, and compare pnHIV patients to both unaffected controls and patients who acquired infection later in life.


TTN gene encodes titin, which is not only an elastic component of muscle contraction but also mediates multiple signalling pathways in striated muscle cells. In recent years, mutations in the TTN gene have been found to be associated with LVNC, but the exact pathogenesis is still not fully clarified.Left ventricular noncompaction (LVNC) is a specific type of cardiomyopathy characterized by coarse trabeculae and interspersed trabecular crypts within the ventricles. Clinical presentation varies widely and may be nonsignificant or may present with progressive heart failure, malignant arrhythmias, and multiorgan embolism. The mode of inheritance is highly heterogeneous but is most commonly autosomal dominant. The TTN gene variant, c.87857G > A (p. Trp29286*), that has not been reported previously. This 43-year-old adult male was hospitalized repeatedly for heart failure. Echocardiography showed reduced myocardial contractility, dilated left ventricle with many prominent trabeculae, and a loose texture of the left ventricular layer of myocardium with crypt-like changes. During the out-of-hospital follow-up, the patient had no significant signs or symptoms of discomfort.In this article, we report a case of an adult LVNC patient with a TTN gene in LVNC and provides a basis for genetic counselling and treatment of this patient. Clinicians should improve their understanding of LVNC, focusing on exploring its pathogenesis and genetic characteristics to provide new directions for future diagnosis and treatment.This case report enriches the mutational spectrum of the  TTN.Left ventricular noncompaction (LVNC) is a specific type of cardiomyopathy. It is characterized by coarse myocardial trabeculae and deep intertrabecular crypts within the ventricle, which communicate with the ventricular cavity and are associated with systolic and diastolic insufficiency. The gross anatomy of the myocardium is “spongy” and contains two layers, including a shallow dense layer on the surface and a thick, loose, nondense layer inside. LVNC can occur alone or in conjunction with congenital heart disease, genetic syndromes, neuromuscular disease, and other types of cardiomyopathies , 2. MostA 43-year-old male patient was hospitalized due to chest tightness and shortness of breath that worsened for 5 h. He was previously diagnosed with LVNC and improved after treatment with furosemide, spironolactone, digoxin, amiodarone hydrochloride, metoprolol tartrate, and perindopril tert-butylamine.He denied a family history of heart disease . Admission examination showed a pulse rate of 100 beats/min and blood pressure of 113/85 mmHg. Lung auscultation shows signs of pulmonary oedema. Heart percussion showed enlargement of the heart border to the left. Additionally, the heart rhythm was definitely irregular, the first heart sound was unequal in strength, the heart sound was low, premature beats could be heard, and no murmur was heard in each valve auscultation area. The rest of the examination did not show any obvious abnormalities.TTN gene, c.87857G > A (p. Trp29286*). This mutation is a nonsense mutation, that can cause the severe loss of function of its encoded protein, titin, and is a heterozygous variant , reduced left ventricular systolic function , left ventricular dilatation , trivial aortic regurgitation, moderate mitral regurgitation, mild tricuspid regurgitation, increased pulmonary artery pressure (47 mmHg), and left ventricular diastolic dysfunction . Adult echocardiography mainly recommends Jenni’s morphologic criteria. (1) The typical two-layer myocardial structure is divided into a dense epicardial layer and a nondense endocardial layer. The ratio of the thickness of the nondense myocardial layer to the dense myocardial layer at the end of left ventricular contraction in adults is > 2. (2) The main ventricular muscles involved are apical, inferior, and lateral ventricular areas. (3) Color Doppler can detect that the intertrabecular crypts communicates with the left ventricle, but does not communicate with the coronary artery circulation. (4) Excluding the combination of other congenital or acquired heart diseases. CMRI is another method for diagnosing LVNC, mostly uses the diagnostic criteria proposed by Petersen et al. (1) The myocardium is divided into two layers, the dense epicardial layer and the nondense endocardial layer. (2) There are coarse trabeculae and deep intertrabecular crypts in the nondense myocardial layer. (3) Ratio of left ventricular end diastolic nondense myocardial layer to dense myocardial layer > 2.3 , 7. CompMYH7, ACTC1, TNNT2, MYBPC3, TPM1, TNNI3, and TNN [In recent years, with the increasing awareness of LVNC and the advancement of diagnostic imaging techniques, the diagnosis rate of LVNC has gradually increased. However, there are still many controversies about its pathogenesis, and the mainstream theories currently include the embryogenesis hypothesis and molecular genetic mechanism , 10. The and TNN , 14.TTN) belongs to the sarcomere protein genes and contains 364 exons. These exons undergo extensive selective splicing, resulting in many subtypes that range in size from 5604 to 34,350 amino acids, and these subtypes are involved in encoding titin [TTN is a common pathogenic gene in dilated cardiomyopathy and hypertrophic cardiomyopathy, and in recent years, the role of TTN in LVNC has received increasing attention. In a meta-analysis published by Elham including 2,271 LVNC patients, TTN was found to be the most common pathogenic gene in LVNC, with a detection rate of 11% [The titin gene , which detects mRNAs harbouring premature termination, codons, and triggers degradation to prevent the accumulation of truncated and potentially harmful proteins [TTN mutations had a poorer prognosis and mRNA sequencing indicated significantly lower mRNA expression levels of TTN, indicating that the mutation triggered the NMD mechanism [TTN mutations lead to mitochondrial dysfunction, reduce autophagic activity in cardiomyocytes, and aberrantly activates the mTORC1 signalling pathway. Dong further confirmed mitochondrial abnormalities in TTN mutant cells, including structural abnormalities observed by electron microscopy, functional abnormalities of reduced extracellular oxygen consumption rate, decreased adenosine triphosphate production and impaired electron transport chain activity. In situ transmission electron microscopy also showed reduced autophagy in mutant cells, accompanied by the activation of the PI3K-Akt-mTORC1 signalling pathway [The molecular mechanism by which proteins , 19. Theechanism . It is a pathway .TTN gene was detected at the chromosome position chr2:179410276, exon 293, codon 87,857 of NM_133378.4 transcript was mutated from G to A, resulting in a nonsense mutation of amino acid 29,286 encoded from tryptophan to stop codon, a heterozygous mutation (Fig. TTN.In this case, direct sequencing of the exons of the patient’s gene by second-generation sequencing technology revealed that the TTN, which enriches the spectrum of pathogenic variants in LVNC and provides help for future genetic diagnosis.This study identified a novel mutation site in


Right ventricular (RV) failure remains a major concern in heart failure (HF) patients undergoing left ventricular assist device (LVAD) implantation. We aimed to measure the kinetic energy of blood in the RV outflow tract (KE-RVOT) – a new marker of RV global systolic function. We also aimed to assess the relationship of KE-RVOT to other echocardiographic parameters in all subjects and assess the relationship of KE-RVOT to hemodynamic parameters of RV performance in HF patients.Fifty-one subjects were prospectively enrolled into 4 groups  as follows: 11 healthy controls, 32 HF patients (8 NYHA Class II and 24 Class IV), and 8 patients with preexisting LVADs. The 24 Class IV HF patients included 21 pre-LVAD and 3 pre-transplant patients. Echocardiographic parameters of RV function  and RV outflow color-Doppler images were recorded in all patients. Invasive hemodynamic parameters of RV function were collected in all Class IV HF patients. KE-RVOT was derived from color-Doppler imaging using a vector flow mapping proprietary software. Kruskal-Wallis test was performed for comparison of KE-RVOT in each group. Correlation between KE-RVOT and echocardiographic/hemodynamic parameters was assessed by linear regression analysis. Receiver operating characteristic curves for the ability of KE-RVOT to predict early phase RV failure were generated.p < 0.005). KE-RVOT was further reduced in the Class IV HF group . KE-RVOT was lower in the LVAD group (25.03 [9.88 to 38.98] mW/m) than the healthy controls group (p < 0.005). KE-RVOT had significant correlation with all echocardiographic parameters and no correlation with invasive hemodynamic parameters. RV failure occurred in 12 patients who underwent LVAD implantation in the Class IV HF group (1 patient was not eligible due to death immediately after the LVAD implantation). KE-RVOT cut-off value for prediction of RV failure was 9.15 mW/m .KE-RVOT (median ± IQR) was higher in healthy controls (55.10 [39.70 to 76.43] mW/m) than in the Class II HF group (22.23 [15.41 to 35.58] mW/m, KE-RVOT, a novel noninvasive measure of RV function, strongly correlates with well-established echocardiographic markers of RV performance. KE-RVOT is the energy generated by RV wall contraction. Therefore, KE-RVOT may reflect global RV function. The utility of KE-RVOT in prediction of RV failure post LVAD implantation requires further study. The increasing number of patients with advanced heart failure has resulted in longer waiting times and increased mortality for patients listed for heart transplantation , 2. Due The kinetic energy of blood in the RV outflow tract (KE-RVOT)—a new marker of RV global systolic function—is a dynamic pressure that reflects the energy generated by the entire RV. We aimed to assess the relationship between KE-RVOT and well-established echocardiographic and hemodynamic parameters of RV performance. We also aimed to investigate whether KE-RVOT predicts RV failure post-LVAD implantation.This prospective study was approved by the institutional review board of our institution, and written informed consent was obtained from all participants. Healthy volunteers, outpatients with heart failure (NYHA Class II) or with an LVAD already implanted, and inpatients with heart failure (NYHA Class IV) were enrolled between November 2017 and March 2019.2. PAPi was calculated as: [(sysPAP– diaPAP)/CVP]. RV failure risk score (RVFRS) was also assessed in the patients with NYHA Class IV heart failure (Echocardiographic parameters of RV function - tricuspid annular plane systolic excursion (TAPSE), St', Et', isovolumic acceleration (IVA), myocardial performance index (MPI)) - were assessed in accordance with published guidelines . Paraste failure . Among tEchocardiographic parameters were assessed, and color Doppler images were stored using a standard diagnostic ultrasound system, Vivid E95 . To calculate KE-RVOT, color Doppler images were processed using the VFM software. Digitized two-dimensional color Doppler cine-loop images were obtained in the parasternal RV outflow view. Images were stored with the VFM configuration, the region of interest was maximized, and the Nyquist limit was set to mitigate aliasing. The ultrasound frequency was 3 MHz, with a frame rate of 30–40 using an M5Sc-D probe. The stored cine-loop images were transferred to EchoPAC®  and converted into HDF-5 files. The HDF-5 files were imported into the VFM software and analyzed. One cardiac cycle was selected for analysis by using two consecutive QRS complexes from the electrocardiogram as the beginning and end points. The right ventricular cavity-endocardial border and pulmonary artery wall were manually traced on the initial frame, and two-dimensional wall tracking was applied to detect wall motion . If the ρ is the density of the blood , v is the velocity vector of the blood flow, and dL is an minute increment of the cross-sectional line . Continuous variables are represented as the median ± IQR. Kruskal-Wallis test was performed for comparison of each group. Tukey Kramer test was performed for further analysis if significant difference was confirmed. Correlation between KE-RVOT and echocardiographic/hemodynamic parameters was assessed by linear regression analysis. Receiver operating characteristic curves for the ability of the KE-RVOT, CVP/PCWP, RVSWi, PAPi, and RVFRS to predict early post-LVAD RVF were generated. 51 subjects were prospectively enrolled and separated into 4 groups: 11 in the healthy control group (C), 8 in the NYHA Class II group (II), 24 in the NYHA Class IV group (IV), and 8 with preexisting LVADs (LVAD). Among the 24 subjects in group IV, 21 subjects subsequently underwent LVAD implantation, and 3 subjects subsequently underwent orthotopic heart transplantation. Patients' clinical characteristics are shown in p < 0.005), group IV , and the preexisting LVAD group  (p < 0.05) (KE-RVOT was significantly higher in group C (55.10 [39.70 to 76.43] mW/m) than in group II  . KE-RVOT < 0.05) .p < 0.0005), groups C and IV (p < 0.0001), groups C and LVAD (p < 0.0001), groups II and LVAD (p < 0.005), and groups IV and LVAD (p < 0.05) (p < 0.0005), groups C and LVAD (p < 0.0001), groups II and LVAD (p < 0.005), and groups IV and LVAD (p < 0.05) (p < 0.05), groups C and IV (p < 0.01), and groups C and LVAD (p < 0.01) (p < 0.005), groups C and IV (p < 0.005), and groups C and LVAD (p < 0.0005) (p < 0.005)  . The val < 0.05) . The val < 0.01) . The val 0.0005) . The val< 0.005) .In the patients with NYHA Class IV HF, CVP/PCWP, RVSWi, and PAPi were 0.39 [0.33 to 0.52], 6.68 [5.23 to 7.79], and 3.32 [2.22 to 5.89] respectively. As for RVFRS, 17 patients had score 0, 1 patient had score 2, 2 patients had score 2.5, and 1 patient had score 4.5.KE-RVOT had significant correlation with all echocardiographic parameters and no correlation with invasive hemodynamic parameters .RV failure occurred in 12 patients among those who underwent LVAD implantation . The overall performance for the prediction of RVF was greatest for KE-RVOT  . SensitiOrthotopic heart transplantation is the most effective treatment for end-stage heart failure . Due to This study demonstrates that KE-RVOT can be used as an indicator of RV function and may be useful as a predictor of post-LVAD RVF. KE-RVOT was significantly lower in the heart failure groups and the preexisting LVAD group compared with healthy controls. The significant reduction in KE-RVOT in the preexisting LVAD group compared to healthy controls may be due to a reduction in RV pulsatility in the preexisting LVAD group. Reduced pulsatility decreases the peak velocity of flow and reduces kinetic energy. There was a non-significant increase in KE-RVOT in the preexisting LVAD group compared to groups II and IV, which is likely due a higher cardiac output in patients with preexisting LVADs. KE-RVOT in group IV was significantly lower than in group II. The overall findings indicate that KE-RVOT may reflect RV function.Although there was significant correlation between KE-RVOT and traditional echocardiographic parameters such as TAPSE, St', IVA, and MPI, KE-RVOT is distinct from traditional echocardiographic parameters. Traditional echocardiographic parameters typically assess regional function. The RV is an anatomically complex three-dimensional structure. It is triangular in shape in sagittal section and crescent-shaped in cross section. Furthermore, RV shape and function are influenced by the interventricular septum, which in turn is affected by ventricular loading conditions. Therefore, it is difficult to assess global RV function with traditional echocardiographic parameters.In contrast, KE-RVOT assesses the flow energy that the entire RV ejects into the RVOT, which reflects both global RV function and pulmonary vascular resistance. KE-RVOT is the hydrodynamic pressure generated by the whole RV pushing blood against pulmonary vascular resistance. Han et al. evaluated KE-RVOT in patients with pulmonary arterial hypertension  and healthy subjects using 4D flow MRI . They deKE-RVOT may also be a good predictor of RVF post-LVAD implantation similar to other well-known predictors such as CVP/PCWP, RVSWi, PAPi, RVFRS. Right to left ventricular end-diastolic diameter ratio is another predictor of RVF before isolated LVAD implantation, however we did not acquire the specific images needed to accurately calculate this ratio in our study . ElevateThe analysis of KE-RVOT requires adequate color Doppler imaging of the parasternal RV outflow view with accurate delineation of the RVOT. The sample size in this study was limited. However, we were able to obtain adequate imaging in all subjects in this study. Larger prospective studies are needed to assess the usefulness of KE-RVOT as a marker for RV function and predictor of post-LVAD RVF.KE-RVOT is a novel noninvasive measure of RV function that differentiate patients at various degree of heart failure patients, and may carry prognostic implication for patients undergoing LVAD implantation. KE-RVOT may reflect global RV function. However, additional studies are required to further evaluate the KE-RVOT and its clinical role.


Coarctation of the aorta (CoA) accounts for approximately 5–8% of all congenital heart defects. Depending on the severity of the CoA and the presence of associated cardiac lesions, the clinical presentation and age vary. Developments in diagnosis and management have improved outcomes in this patient population. Even after timely repair, it is important to regularly screen for hypertension. Patients with CoA require lifelong follow-up with a congenital heart disease specialist as these patients may develop recoarctation and complications at the repair site and remain at enhanced cardiovascular risk throughout their lifetime. Coarctation of the aorta (CoA) is one of the most common congenital heart defects (CHD), accounting for approximately 5–8% of CHD , with anThere have been significant advances in the diagnosis and management of CoA with the advent of multi-modality imaging, rapid advances in interventional techniques and the accumulation of long-term data for patients who have been operated on in childhood. The development of coordinated care for patients with adult congenital heart disease in the developed world has also led to improvements in outcomes. There is increasing evidence that CoA represents a generalised arteriopathy, leading to an enhanced cardiovascular risk across the patient’s lifetime and the need for lifelong follow-up with an adult congenital heart disease specialist.The anatomist Morgagni described CoA of the aorta in 1760, with the first operation being performed by the Swedish surgeon Clarence Crafoord in 1944, who completed an end-to-end anastomosis of the aorta on two patients aged 12 and 27 years . CoA repBeyond a purely anatomical description, however, the definition of CoA within international guidelines relies on haemodynamic data from cardiac catheterisation ,6. For eHowever, the haemodynamic definition of CoA may have significant limitations. This was highlighted in recent work modelling fluid dynamics in CoA, which demonstrated the dependence of the trans-stenotic gradient on systemic compliance . SystemiCoA is associated with several cardiac lesions, with associated congenital cardiac anomalies being reported in a majority of patients with CoA in recent case series ,9. BicusThe genetic basis of CoA is poorly understood, although there is a significant risk of familial recurrence suggesting a heritable component . CandidaExtension of ductal tissue into the aorta, causing constriction of the aorta when the ductus arteriosus closes at birthHemodynamic reduction in LV forward flow leading to abnormal development of the aorta, which would be supported by the association of other left-sided obstructive lesions with CoAAbnormalities of the migration of neural crest cells which are the origin of parts of the aorta and left ventricular outflow tract and valves .There are a number of theories regarding the pathophysiology of CoA, which can be summarised as follows:The most studied of these theories is the ductal theory, with substantial evidence in the literature for the histological and biomolecular similarity of ductal and CoA tissue.Histologically, normally developed ductal tissue demonstrates loosely arranged smooth muscle cells without elastic fibres. Fetal ductal arteriosus specimens have been shown to display advanced smooth muscle cell differentiation compared to adjacent aortic tissue in a number of studies, with electron microscopy revealing the presence of well-developed contractile myofilaments in ductal tissue which is thought to be an important contributor to ductal closure soon after birth ,22. DediElzenga and Gittenberger-de Groot et al. studied 45 CoA specimens obtained at surgery. CoA specimens were characterised by the presence of intimal thickening, with ductal tissue forming half of the total circumference of the CoA segments in comparison to normal aortas where it formed less than one-third of the circumference . CoA segA deeper understanding of the cellular mechanism of CoA is important in guiding therapeutic approach. Given the presence of apoptotic cells in the CoA segment, there may be a higher risk of aortic aneurysm when surgical techniques are employed that leaves abnormal ductal tissue intact within the aorta such as subclavian flap repair and patch aortoplasy, when compared to end-to-end anastomosis of the aorta, which completely resects the abnormal tissue .The ductal theory does not however explain the pathophysiology of CoA in its entirety though, since the coarctation site can be at some distance from the site of the ductus arteriosus. Since the vascular smooth muscle cells within the ascending aorta and arch are derived from the cardiac neural crest, it has been suggested that CoA may be a disorder of neural crest development. Animal studies which knock out genes relating to neural crest development have supported this theory, with disruption of PAX3 and NOTCH signalling in the cardiac neural crest leading to both aortic valve abnormalities and thickening of the aortic wall ,28.In the neonate with a discrete significant CoA and no other cardiac lesions, there may be little evidence of a significant pathology under the time of ductal closure, when lower limb perfusion becomes compromised. It is important to note that even in a neonate with a normal echocardiogram soon after closure of the duct, clinically apparent CoA may develop later on . The claWhereas neonates with a discrete CoA may present this way, those with a less severe narrowing may have a delayed presentation even as far as into late adulthood. These patients will usually develop a collateral circulation, raised blood pressure and compensatory left ventricular hypertrophy, followed by LV failure if left untreated. The prognostic benefit of intervention for CoA later in life is uncertain. CoA represents a lifelong condition. Even after an apparently successful repair in infancy, there is a high rate of reoperation, reported to be around 50% by the fifth decade. A decreased life expectancy has been shown in long-term follow-up data of repaired CoA patients when compared to the general population, with a high rate of adverse cardiovascular events ,31. MultPrenatal diagnosis of CoA is notoriously challenging, with a high rate of false positives on pulse oximetry and fetal echocardiography-based screening, leading to considerable anxiety for families and allocation of limited paediatric and neonatal resources to the admission and surveillance of neonates with equivocal findings. False positive rates range from 48 to 94% ,33,34. TStudies analysing the performance of fetal echocardiography in the prenatal diagnosis of CoA have found that multiparametric models have a superior diagnostic performance to any one quantitative echocardiographic measure. These models rely on a variety of measurements including those of the LV inflow, as well as measurements comparing the relative ratios of various components of the right and left heart outflows to predict the presence of true CoA. Due to the heterogeneity of the quantitative parameters used, it has been difficult to compare the performance of these models in a meaningful way or integrate these, and none have been adopted into widespread clinical practice. Qualitative data such as the presence of a CoA shelf or hypoplastic arch have also been shown to be predictive of a true diagnosis, though the definition of neonatal aortic arch hypoplasia in itself remains heterogeneous . Transthoracic echocardiography (TTE) remains the first line of investigation for diagnosis and follow-up of children and adults with CoA. The suprasternal notch view allows visualisation of the aortic anatomy and measurement of Doppler-based gradients across the site of the CoA . Colour Limitations of this modality include its operator dependency, as well as the variability in echocardiographic windows between patients which can preclude its use. There is also limited visualisation of extracardiac structures. Transoesophageal echo (TOE) has relatively limited clinical use in the context of CoA due to its comparatively invasive nature and limited visualisation of the aortic arch. Cardiac computed tomography (CT) has the highest resolution of the non-invasive imaging modalities and allows detailed assessment of the cardiac and non-cardiac structures, including the entire aorta and its branches, collaterals, vascular and extracardiac structures to be ascertained within one examination. Short scanning times allow its use in the paediatric population without the need for sedation, with the possibility of acquiring a complete data set in one or several cardiac cycles, without the need for breath holding. CT does not suffer from the problem of artefacts where a CoA site has been stented.Cardiac computed tomography (CT) has the highest spatial resolution of the non-invasive imaging modalities and allows detailed assessment of the cardiac and non-cardiac structures, including the entire aorta and its branches, collateral mapping, surrounding vascular and extracardiac structures to be ascertained within one examination. Short scanning times facilitate its use in the paediatric population, with a short duration of light or milk sedation and the possibility of acquiring a complete data set in one or few cardiac cycles, and overcome the need for breath holding. New reconstruction software and kernels significantly reduce artefacts where a CoA site has been stented . An important drawback of cardiac CT is the radiation dose, which is an important factor to consider in a paediatric population destined for lifetime follow-up and repeat cross-sectional imaging. However with the introduction of the multi and new-detector  CT with the recent acquisition techniques, the radiation dose associated with cardiac CT has markedly reduced in the last 20 years. Another important limitation of CT is the lack of haemodynamic assessment, which forms a crucial part of the follow-up of these patients. Cardiac magnetic resonance (CMR) imaging has a number of advantages compared to the other modalities, being the gold standard in non-invasive assessment of cardiac structure and function as well as providing non-invasive tissue characterisation through late gadolinium (LGE) imaging. CMR plays a crucial role in the contemporary diagnosis and management of patients with congenital heart disease. With the advent of 4D flow CMR, we are able to integrate sophisticated haemodynamic data with detailed anatomical information for the first time, which is likely to improve our understanding of the heterogenous clinical course seen in many of the patients we treat, including those with CoA . In the Fetal CMR studies of CoA have demonstrated the potential of 4D CMR to improve prenatal diagnosis of CoA, a notoriously challenging diagnostic area. The importance of flow analysis in CoA may be predicted given the hypothesis that CoA may be a consequence of abnormal or reduced left ventricular flow in fetal life. A recent study by Lloyd et al. demonstrated the superior performance of a multivariate model derived from fetal 4D flow CMR in the third trimester compared to that reported for fetal echocardiographic screening . In a muCMR has also been utilised in the research setting to refine our understanding of operated aortic anatomy and haemodynamics, including the impact of aortic arch shape  on wall Cardiac catheterisation is the gold standard for haemodynamic assessment of CoA and allows high-resolution visualisation of the anatomy of the aortic arch, as well as assessment of any collaterals. A peak-to-peak gradient of >20 mmHg on catheterisation is considered to be evidence of significant CoA in international guidelines ,6. The sThe role of diagnostic catheterisation is increasingly being superseded by cross-sectional imaging in the surveillance of patients following surgical repair; however, it retains importance where catheter-based intervention for re-stenosis is being considered, whether this is balloon angioplasty or stenting.Untreated CoA has a dismal prognosis, with a 50% mortality rate by age 30 reported in Maude Abbot’s series of 200 patients with unrepaired CoA. Death occurred due to serious sequelae such as aortic rupture, endocarditis and heart failure . SurgicaA number of surgical techniques have been employed for the repair of CoA. In general, the approach is via a left postero-lateral thoracotomy. A reasonably low mortality and morbidity rate from surgery is reported in contemporary studies with 0.54% 30-day mortality reported in a recent study . RecogniTechniques used include end-to-end anastomosis, which involves complete resection of the CoA segment with anastomosis of the two ends of the aorta. Subclavian flap repair (SF) is where the subclavian artery is resected including the CoA segment, with the flap then reversed and used to repair the aorta. Extended end-to-end repair is employed where there is coexistence of a hypoplastic aortic arch and an interposition graft may be used. Patch augmentation is no longer in use, being associated with a high incidence of aortic aneurysms  53]..53].Studies comparing these surgical techniques are heterogeneous in a number of aspects, and therefore the superiority of one surgical technique over another remains in doubt in terms of recoarctation and reoperation rates. It has not proved possible to combine these studies in a meta-analysis, with variable hemodynamic definitions of CoA and recoarctation being employed across the literature. In addition, a number of these cohorts are mixed with different proportions of patients with additional congenital diagnoses, ranging from hypoplastic aortic arch and VSD to more complex congenital conditions such as hypoplastic left heart syndrome. There are a number of observational studies that have attempted to answer the question regarding the best surgical technique through a comparison of long-term outcomes following CoA surgery. These show a range of conflicting results, with the majority showing no difference between various techniques ,55. TherAlthough surgery remains the first line in children diagnosed with CoA, percutaneous intervention may be used as a strategy in high-risk neonates as definitive treatment, or as a bridge to surgery. Balloon angioplasty and stenting are often used in the post-surgical repair setting, for relief of recoarctation. Catheter-based treatment is recommended as the first line in adults diagnosed with CoA or recoarctation in the latest iteration of the European Society of Cardiology Guidelines for Adult Congenital Heart Disease . The latWhere a percutaneous approach is preferable, balloon angioplasty is typically used in infants < 1 year instead of stent implantation, due to the need for a larger sheath for the latter treatment. Early reports of the long-term outcomes post balloon angioplasty reported a high rate of aneurysm formation compared to a surgical strategy. This, combined with the favourable reintervention rates of <10% reported in longitudinal follow-up of post-surgical repair patients, has led to surgery being considered the first line in this population. However, a recent study of 68 infants aged 3–12 months who underwent balloon angioplasty for native CoA showed this to be a safe and effective management strategy, with early procedural success in 88% (defined as a gradient < 20 mmHg), with 81% freedom from reintervention at 10 years post-procedure. Endovascular stenting has been used preferentially to balloon angioplasty in children > 10 kg due to superior hemodynamic results, lower risk of aneurysm formation, aortic wall injury and restenosis  57,58].,58.57,58The role of stenting in smaller children weighing <20 kg has also been studied . Though Longitudinal data on repaired CoA reveals a plethora of late complications in spite of contemporary surgical practice and close follow-up. Those who have had a CoA repair continue to have a reduced life expectancy compared to age-matched counterparts in the general population, with only 66% of patients in a recently reported cohort surviving to age 70 . MortaliRecoarctation rates of 30–59% have been reported, with some studies supporting the notion that end-to-end anastomosis is associated with a lower reintervention rate ,55,65. AHypertension is reported in 25–62% of patients post CoA repair, with the prevalence varying between studies based on the methodology used to define hypertension, with some studies employing 24 h ambulatory BP readings in addition to office or home readings . Risk faApproximately 14% of those with surgically repaired CoA develop dilatation of the aorta especially at the site of previous repair, typically defined as a repair site—diaphragm ratio of 150% . ApproxiA higher risk of ischaemic and haemorrhagic stroke is observed in CoA patients, in particular subarachnoid haemorrhage as a consequence of the rupture of cerebral aneurysms, which are found more commonly, with a prevalence of 10% in a screening study compared to approximately 2% in the general population ,78,79,80The role of premature coronary artery disease (CAD) in driving early mortality in repaired CoA has been controversial in the literature. Although CAD is the primary mode of death in older long-term follow-up studies of repaired CoA, the association of CoA with premature coronary artery disease independent of traditional risk factors such as hypertension has not been conclusively demonstrated ,83,84,84CoA leads to pressure overload of the left ventricle and adverse left ventricular remodelling. Histologically, this is characterised by myocyte hypertrophy, disarray and fibrosis. Ensuing alteration in myocardial mechanical properties manifests in the form of diastolic and systolic dysfunction, with LV failure being a significant cause of mortality . Even afPregnancy is categorised as an intermediate risk in international guidelines in the setting of repaired CoA (modified WHO classification II–III) and high risk in those with unrepaired CoA (mWHO IV) ,90,91. TCoA remains a diagnostic and therapeutic challenge due to the difficulties of prenatal diagnosis, wide-ranging anatomical variation, long-term adverse cardiovascular sequelae of abnormal haemodynamics and impaired systemic vascular function, which are still not fully understood. Even where there is timely repair, these patients remain at enhanced cardiovascular risk throughout their lifetime. In the adult population, it is important to regularly screen for hypertension as well as repair site-related complications with interval surveillance cross-sectional imaging. The increasing use of advanced imaging techniques such as 4D flow MRI, which is able to noninvasively combine anatomical and haemodynamic data, is likely to refine the prognostication of these patients which is sorely needed. The reduced life expectancy of these patients highlights a need to more accurately phenotype this heterogenous patient population to help better understand the pathophysiological factors behind enhanced cardiovascular risk, despite successful repair, and the best indications and optimal timing for reintervention.


Despite polysomnography being the gold standard method of diagnosing obstructive sleep apnea (OSA), it is time-consuming and has long waiting lists. Alternative methods including questionnaires and portable sleep devices have been developed to increase the speed of diagnosis. However, most questionnaires such as the STOP-BANG questionnaire (SBQ) are limited due to low specificity. This study evaluated the value of SBQ to screen for OSA and compared it with the oxygen desaturation index (ODI) and their combination.This retrospective study included patients who completed the SBQ and underwent a night at the sleep lab or home sleep testing. The ODI was extracted from these sleep study reports. The combination of SBQ with ODI and their individual scores were compared with apnea–hypopnea index (AHI) in terms of their accuracy in diagnosing OSA. Sensitivity, specificity, and area under the curve (AUC) for different severities of OSA were calculated and compared.Among 132 patients, SBQ showed a sensitivity of 0.9 and a specificity of 0.3 to screen for OSA. As the severity of OSA increased, the sensitivity increased whilst specificity decreased for both measurements. ODI achieved an increased specificity of 0.8 and could correctly diagnose OSA 86% of the time which was better than SBQ’s 60%. For all severities of OSA, ODI alone displayed a larger AUC than SBQ and similar AUC to their combination.ODI produced a higher specificity and AUC than SBQ. Furthermore, ODI combined with SBQ failed to increase diagnostic value. Therefore, ODI may be the preferred way to initially screen patients for OSA as an easy-to-use alternative compared to SBQ. Obstructive sleep apnea (OSA) is a sleep-related breathing disorder (SBD) characterized by intermittent obstruction and cessation of airflow in the upper airway (apnea). It can also be characterized by the temporary narrowing of the airway which results in the reduction of airflow (hypopnea). The narrowing is caused by the relaxation of throat muscles during sleep . The preThe gold standard examination for diagnosing OSA is overnight polysomnography (PSG) in a sleep laboratory. PSG can accurately monitor sleep, blood oxygen levels, respiratory effort and airflow, limb movements, heart rate, and body position. However, the waiting lists can be quite long due to limited bed space . The morThere are some limitations to using PSG and HSAT. One is the first-night effects of sleeping in a laboratory connected to PSG or at home with HSAT. Both tests can increase sleep onset latency and reduce sleep efficiency which can affect the AHI score . In thisCheaper and less time-consuming methods of evaluating possible OSA are questionnaires such as the Berlin questionnaire, STOP-BANG  questionnaire (SBQ), and the NoSAS  –15. A syTherefore, in order to enhance the speed and accuracy of OSA diagnosis in sleep medicine outpatient departments, the following aims were investigated: (a) testing the strength of the individual and the combined SBQ and ODI with AHI when diagnosing OSA, and (b) testing both the individual and the combined validity of the ODI and SBQ with the AHI when diagnosing OSA. It was expected that either ODI alone or in combination with SBQ would have higher specificity and greater area under the curve (AUC) than SBQ alone.The ethics committee of the Charité–Universitätsmedizin Berlin approved the study protocol, and informed consent was obtained from all patients.During the first visit, all patients completed the previously validated German version of the SBQ , 20, andThe SBQ consists of 8 yes/no questions, each negative answer is scored as 1 and each positive is scored as 0. A total score of ≥ 3 but < 5 is classified as having an intermediate risk of OSA, and a high risk of OSA is between 5 and 8 points. High sensitivity can be seen when using a cut-off score of ≥ 3 with the AHI when defining OSA: 84% in detecting mild, 93% in detecting moderate to severe, and 100% in detecting severe. However, their specificities were low at 56%, 43%, and 37%, respectively . As mentAll analyses were computed in SPSS software version 22.0. A Spearman’s correlation coefficient was calculated to measure the strength of the relationship between the AHI with SBQ, ODI, and their combination. This was to identify whether each measure follows in the same direction as AHI.An additional Spearman’s correlation coefficient was conducted to measure the strength of the relationship between different levels of AHI severity with SBQ, ODI, and their combination. This was to identify whether different severity levels of AHI are more or less related to each measure.Positive predictive value (PPV) and negative predictive value (NPV) were calculated to validate the sensitivity and specificity of the cut-off values SBQ ≥ 3, ODI ≥ 5, and their combination. We also tested a model that combines ODI with the SBQ by logistic regression. This will inform us whether the combination increases the sensitivity and specificity of each measure.Z-tests to assess their overall performance. Z-tests are a nonparametric test for 2 independent samples. They were used to compare the AUC characteristic derived from the same cases. Furthermore, the optimal cut-off values of ODI and SBQ in the AUC analysis were evaluated to achieve the most accurate prediction of OSA diagnosis .In addition to this, receiver operating characteristic curves (ROCs) were performed to assess the diagnostic value of the ODI alone, SBQ alone, the combination of the two, and the logistic regression for different severities of AHI. The AUC produced from the ROCs range from 0.50 (no diagnostic ability) to 1.0 (perfect diagnostic ability) and can also be confirmed with a Youden statistic. The closer the value is to 1, the higher the diagnostic value the analysis holds. The differences in AUC calculated by the ROC characteristics were compared by 2, and an ODI of 13.4 ± 16.32. All patients reported at least one suspected OSA symptom, the most common were snoring (72%) and hypertension (47%). From this sample, 53% were diagnosed with OSA  and 47% with no OSA.The sample consisted of 224 patients who visited the outpatient department in the interdisciplinary sleep medicine center at the Charite-Universitatsmedizin in Berlin from January 2017 to January 2018. Ninety-two patients were excluded due to either incomplete follow-ups, SBQs, and/or clinical data, which left 132 patients to be included in this study. The demographic and mean SBQ responses from the patients are shown in Table p < 0.05 and r = 0.914) whilst the SBQ  showed a weaker positive correlation with AHI. It was also found that as the ODI score increases, so did the SBQ score (p < 0.05 and r = 0.451). This suggests that as AHI scores increase so does ODI and SBQ. However, the relationship is stronger between ODI and AHI. Table ρ of 0.493 and 0.796, respectively).There were significant positive correlations between the AHI, ODI, and SBQ mutually for patients with OSA overall. The ODI highly correlated with the AHI  which was much higher than SBQ (62%). The sensitivity increased as the severity of OSA increased , and the NPV also increased . The specificity of ODI decreased as the severity of OSA increased , and the PPV decreased .The combination of SBQ with ODI and a logistic regression model (SBQ + ODI) showed the best performance of specificity in all severity levels of OSA . There was also a decrease in PPV as the severity of AHI increased. However, these values were still higher than SBQ and ODI alone . One consequence of this combination was that the sensitivity was slightly lower when ODI and SBQ measures were evaluated separately.Z-test, all of which were significantly larger (p < 0.05) than SBQ ≥ 3 . However, when the SBQ was combined with ODI, it did not significantly contribute to the value of ODI (p ≥ 0.46).See Figs. In summary, ODI ≥ 5 had higher sensitivity, specificity, and a larger AUC than SBQ ≥ 3 for screening all OSA. Furthermore, ODI showed higher sensitivity, a slightly lower specificity, and the same overall value as the logistics model.See Table This study showed that using the ODI alone may serve as a good preliminary assessment of OSA whilst waiting for a full diagnosis from HSAT or PSG. However, the combination of SBQ failed to increase the diagnostic value of ODI, and the rate of accepting a false negative slightly increased.A positive correlation was detected for both ODI and SBQ with AHI. This suggests that as the AHI severity increases, the SBQ and the ODI scores decrease. When breaking this down by severity of AHI, a strong positive relationship can be seen in ODI alone with moderate and severe OSA whilst the SBQ displayed non-significant relationships. On the other hand, SBQ and ODI had no significant positive correlation when diagnosing mild OSA. This suggests that ODI alone would be better at diagnosing moderate and severe OSA than SBQ. Considering possible moderating factors, the low correlation between SBQ and AHI might have been affected by the small sample. Another reason could be that there was an uneven gender split of 74% of males compared to a low proportion of females (26%).Our findings indicated that SBQ alone and ODI alone demonstrated high sensitivity for each severity of OSA classified by the AHI. However, the specificity scores of SBQ for each severity level remained low. In terms of the PPV and NPV, there is a greater likelihood of accepting false positives than false negatives which means that if SBQ alone were used individually with AHI, then there would be a greater possibility of misdiagnosing the severity of OSA, especially moderate and severe as their specificity scores are low. Nagappa et al.  conductePrevious studies have focused on improving the PPV and specificity of the SBQ by combining it with different tools , 23. Senr = 0.914), which suggests that this model showed a good performance to screen all severities of OSA. Therefore, overnight oximetry seems to be an inexpensive, readily available, and straightforward tool to screen for OSA. Previous studies have also emphasized the accuracy of ODI as a tool to detect SBD and suggested it should be an essential assessment criterion for diagnosis [As mentioned previously, a strong correlation was found between ODI and AHI in the multiple logistic analysis r = 0.14, whichiagnosis , 28. Masiagnosis  found thThe diagnostic ability of SBQ, ODI, and their combination at different cut-offs has been investigated previously. Chung et al.  found thA limitation of this study is the small sample size. Some of the patients may have given more extreme answers on the SBQ than others. This could skew the accuracy and comparability of the value. Therefore, larger studies are needed to confirm the findings of this study.In addition, the correlation and ROC analyses in this study reported contrasting results for the relationship between the AHI with the combination of ODI and SBQ. However, this was mostly dependent on different cut-off values of the SBQ calculated for different severities of OSA.A further limitation is that this study evaluated the ODI adopted from sleep study reports instead of portable nocturnal pulse oximetry. This means that the ODI was not scored independently from the AHI/REI, whereas it is possible to do this with portable oximetry devices. These devices can record more data and provide detailed information about the oxygen level at night (including a detailed graph and 4% desaturation events). Therefore, the value produced by these new devices should be studied further.This study attempted to improve the diagnostic ability of the SBQ in screening and predicting the degree of OSA by combining it with ODI. According to the findings, ODI alone had a higher sensitivity and specificity than SBQ, and the combination with SBQ failed to provide additional diagnostic value. Therefore, a simple portable nighttime pulse oxygen saturation monitoring device may be the preferred way to initially screen for potential OSA with comparatively low cost compared to PSG.


The impairment of atrial function and atrial-ventricular coupling in diseases with left ventricular (LV) hypertrophy has been increasingly recognized. This study compares left atrium (LA) and right atrium (RA) function, as well as LA-LV coupling, in patients with hypertrophic cardiomyopathy (HCM) and hypertension (HTN) with preserved LV ejection fraction (EF), using cardiovascular magnetic resonance feature tracking (CMR-FT).Fifty-eight HCM patients, 44 HTN patients, and 25 healthy controls were retrospectively enrolled. LA and RA functions were compared among the three groups. LA-LV correlations were evaluated in the HCM and HTN groups.p < 0.05). Reservoir and conduit functions were more impaired in HCM patients compared to HTN patients (p < 0.05). LA strains demonstrated significant correlations with LV EF, LV mass index, LV MWT, global longitudinal strain parameters, and native T1 in HCM patients (p < 0.05). The only correlations in HTN were observed between LA reservoir strain (ɛs) and booster pump strain (ɛa) with LV GLS (p < 0.05). RA reservoir function  and conduit function  were significantly impaired in HCM and HTN patients (p < 0.05), while RA booster pump function  was preserved.LA reservoir , conduit , and booster pump  functions were significantly impaired in HCM and HTN patients compared to healthy controls (HCM vs. HTN vs. healthy controls: ɛs, 24.8 ± 9.8% vs. 31.3 ± 9.3% vs. 25.2 ± 7.2%; ɛe, 11.7 ± 6.7% vs. 16.8 ± 6.9% vs. 25.5 ± 7.5%; ɛa, 13.1 ± 5.8% vs. 14.6 ± 5.5% vs. 16.5 ± 4.5%, LA functions were impaired in HCM and HTN patients with preserved LV EF, with reservoir and conduit functions more affected in HCM patients. Moreover, different LA-LV couplings were apparent in two different diseases, and abnormal LA-LV coupling was emphasized in HTN. Decreased RA reservoir and conduit strains were evident in both HCM and HTN, while booster pump strain was preserved. MyocAlthough both HCM and HTN present with pathological LVH, they are two distinct diseases with specific pathophysiological mechanisms. HCM is the most common inheritable heart disorder activated via genetic pathways , 14, whiOn the other hand, the right heart, previously considered a “dispensable” part of the heart, has recently become a research hotspot in pathophysiological conditions such as heart failure and pulmonary hypertension . NumerouTherefore, the present study aims to compare LA function between patients with HCM and HTN with preserved EF and further explores LA-LV coupling in these two diseases. We also investigate the feasibility of CMR-FT in RA deformation assessment and whether early RA dysfunction can be detected in HCM and HTN patients.2.2.1.We retrospectively enrolled 58 consecutive HCM and 44 HTN patients between January 2019 and November 2022. The HCM inclusion criteria were as follows: CMR demonstrating LVH  without other hypertrophy-causing diseases . HTN was2.2.2.2.1.All CMR images were obtained using two clinical 3.0-T MR scanners . Transverse dark blood images were acquired with the following parameters: slice thickness: 8 mm; TR: 882 ms; TE: 40 ms; FOV: 344 mm × 343 mm. Balanced SSFP breath-held cine images were acquired in the two-chamber, three-chamber, four-chamber, and 8–11 equidistant short-axis planes, covering the entire LV and RV. Typical imaging parameters included: slice thickness: 8 mm; TR: 3.4 ms; TE: 1.1–1.5 ms; FOV: 360 mm × 315 mm; spatial resolution: 1.3 mm × 1.3 mm × 8.0 mm; flip angle: 60–70°; temporal resolution 42 ms.2.2.2.Conventional size parameters were obtained from dark blood images and balanced SSFP cine images. LV EDD was measured at the papillary level of LV short-axis cine images, and RV EDD was measured on the extension cord of the left measuring line. MWT was defined as end-diastolic wall thickness selected in the thickest segment from the LV short-axis cines without involving trabeculations from both ventricles. AP diameters of LA and RA were measured on transverse dark blood images.Functional and strain analyses were performed on balanced SSFP cine images using dedicated software . The following LV functional parameters were calculated from all of the phases on the short-axis and three long-axis cine images in end-systole and end-diastole: LV EDV, LV ESV, LV EF, and LV mass. The following RV functional parameters were calculated from all of the phases on the short-axis and four-chamber cine images in end-systole and end-diastole: RV EDV, RV ESV, RV EF, and RV mass. Papillary muscles were included in the volume and excluded from the mass calculations.LV and RV strain measurements were carried out based on long-axis images by tracing endocardial and epicardial borders at end-systole and end-diastole. Endocardial and epicardial borders were semi-automatically detected and manually corrected, excluding the papillary muscles. Then, all frames throughout the entire cardiac cycle were propagated. LV GLS was derived from two-, three-, and four-chamber views, and RV GLS was derived from a four-chamber view. Associated peak global systolic and diastolic strain rates (SRs) were obtained simultaneously. Native T1 mapping of LV was obtained from the basal and mid-ventricular short-axis sections before contrast medium administration.Vmax − Vmin) × 100%/Vmax; EF passive = (Vmax − Vpac) × 100%/Vmax; and EF booster = (Vpac − Vmin) × 100%/Vpac.LA volumes were calculated using the biplane area–length method . Manual For strain analysis, LA endocardial and epicardial borders were tracked in two- and four-chamber views . RA endo2.3.Intra-observer reproducibility for global strain and SR parameters was assessed in 30 randomly selected subjects  with a four-week interval between analyses (H.L. with four years of cardiovascular MRI experience). Inter-observer reproducibility was assessed in the same 30 subjects by comparing results from a second experienced observer (T.W. with five years of cardiovascular MRI experience).2.4.t-test for normally distributed data or Mann–Whitney U-test for non-normally distributed data. Categorical variables were evaluated using chi-square test or Fisher's exact test. Pearson's or Spearman's correlation analysis was performed to investigate the relationship between LA strains and LV parameters. The correlation was considered weak if r was <0.5, moderate if r was between 0.5 and 0.7, and strong if r was >0.7  were performed using independent was >0.7 . Intra- 3.3.1.p < 0.05). No significant difference was observed in the rate of diabetes, resting SBP, and NYHA distribution between HCM and HTN patients.3.2.p < 0.05; p < 0.05).HCM and HTN patients exhibited higher LV massi, LV EDD, LV MWT, RV massi, and RV EDD compared to healthy controls . Native T1 was elevated in HCM patients, but no significant difference was noted in HTN patients compared to healthy controls . Impaired RV GLS was observed in HCM patients, but no significant difference was found in HTN patients .Impaired LV GLS and peak diastolic global longitudinal strain rate (dGLSR) were observed in HCM and HTN patients compared to healthy controls. Furthermore, HCM patients had lower levels of GLS, sGLSR, and dGLSR compared to HTN patients . Vmaxi, Vpaci, and Vmini, followed by HTN patients and healthy controls (p < 0.05).HCM and HTN patients had larger AP diameters of LA and RA compared to healthy controls, with HCM patients showing the highest values (p < 0.05). Moreover, LA reservoir function  and conduit function  were more impaired in HCM patients compared to HTN patients , conduit function , and booster pump function  were significantly reduced in HCM and HTN patients compared to healthy controls  and conduit strain  were significantly impaired in HCM and HTN patients compared to healthy controls . In addition, RA conduit function  was more impaired in HCM patients compared to HTN patients (p < 0.05). However, RA booster pump function  was preserved in both HCM and HTN patients (p > 0.05).Although RA volumetric parameters, including 3.4.p < 0.05; p < 0.05; Significant correlations were found between LA reservoir strain (ɛs), conduit strain (ɛe), and booster pump strain (ɛa) with LV EF, LV massi, LV MWT, global longitudinal strain parameters, and native T1 in HCM patients  LA reservoir, conduit, and booster pump functions were impaired in both HCM and HTN patients, with reservoir and conduit functions more impaired in HCM patients; (2) HCM and HTN exhibited different LA-LV couplings, with significant correlations between LA strains  and LV compliance and systolic strain parameters in HCM, while in HTN, correlations were only found between LA reservoir strain (ɛs) and booster pump strain (ɛa) with LV GLS; (3) RA reservoir and conduit strains were reduced prior to RV dysfunction in both HCM and HTN patients, while booster pump function was preserved.Based on the structural parameter data, LA morphological remodeling was observed in our patients, as evidenced by enlarged LA size and volume. LA reservoir and conduit functions were impaired in both HCM and HTN patients, which was consistent with previous studies , 30, 31.Interestingly, the present study showed that different atrio-ventricular interactions occurred in the two different diseases. Significant correlations were found between LA strains  and LV compliance  as well as systolic parameters  in HCM patients. In contrast, fewer correlations were found in HTN, with the only correlation observed between LA strains  and impaired LV GLS. These findings indicate that HCM and HTN display different patterns of LA-LV coupling, which is in line with previous STE-based studies , 34. In RV hypertrophy and dysfunction are frequently observed in both HCM and systemic hypertension , 40. PreThere are some limitations to our study. First, the study sample size was relatively small, and the cohort predominantly consisted of Chinese participants. Therefore, these findings require further validation and confirmation in larger-scale studies with a more diverse population. Second, subgroup analysis was not performed in this study due to its small sample size. The HCM cohort included patients with and without obstruction of the LV outflow tract, and patients with and without LV hypertrophy were included in the HTN cohort. Third, since some of our patients did not undergo the hematocrit (HCT) laboratory test on the day of the CMR examination, extracellular volume fraction (ECV) data could not be obtained. Lastly, due to the thin RA wall and the tricuspid valve attachment point not being as clearly visible as the bicuspid valve, tracking the RA endocardial and epicardial borders was more challenging than tracking those of the LA. Furthermore, while the LA outline was tracked on two long-axis views, the RA outline was tracked on only one long-axis view. Consequently, RA strains and SRs demonstrated weaker intra- and inter-observer reproducibility compared to the LA in the present study.5.This study demonstrated the feasibility of using CMR-FT in evaluating RA deformation and provided insight into the differences in LA function and LA-LV coupling between patients with HCM and HTN. LA reservoir, conduit, and booster pump functions were impaired in both HCM and HTN patients, with reservoir and conduit functions more impaired in HCM patients. HCM and HTN exhibited different patterns of LA-LV coupling, which may have clinical implications for understanding the disease course and developing targeted therapies. Furthermore, RA structural remodeling and dysfunction were found to occur before RV dysfunction in both HCM and HTN patients. Future larger-scale studies with diverse populations are needed to validate and confirm these findings, potentially leading to improved understanding and management of these diseases.


To investigate the risk factors of left ventricular diastolic dysfunction in maintenance hemodialysis (MHD) patients.We retrospectively collected data from 363 hemodialysis patients who were on dialysis for at least 3 months at January 1, 2020. According to the echocardiogram results, these patients were divided into left ventricular diastolic dysfunction (LVDD) group and non-LVDD group. The differences in basic data, cardiac structure and functiona between the two groups were analyzed. Logistic regression analysis was used to analyze the risk factors of cardiac diastolic dysfunction in MHD patients.p < 0.05) proportion of cardiac structural abnormalities such as left ventricular hypertrophy, left heart enlargement and systolic dysfunction. Multivariate logistic regression analysis showed that the risk of LVDD was significantly increased in elderly MHD patients older than 60 years , and left ventricular hypertrophy was also significantly associated with LVDD .Compared with the non-LVDD group, patients in the LVDD group were older, with an increased proportion of coronary heart disease, more prone to chest tightness, shortness of breath. Simultaneously, they had a significantly increased (According to research, both age and left ventricular hypertrophy are risk factors for LVDD in MHD patients. It is recommended that early intervention for LVDD should be implemented to improve the quality of dialysis and reduce the incidence of cardiovascular events in MHD patients. Cardiovascular disease (CVD) is a common comorbidity in chronic kidney disease (CKD) patients , it is aThis was a retrospective cross-sectional study in which all patients that underwent dialysis for at least 3 months at January 1, 2020 were included.age ≥ 18 years, regular hemodialysis patients whose hemodialysis age ≥ 3 months, consent to the study and signed informed consent.acute myocardial infarction three months before enrollment. Severe heart valve disease or rheumatic heart disease and patients who disagree with the study.The information we collected included age, gender, hemodialysis age (months), the primary disease of kidney and complications, such as hypertension, diabetes, coronary heart disease and heart failure. Dialysis frequency and average ultrafiltration capacity per time were collected. Venous blood was collected before dialysis, and we also collected the test items involving hemoglobin, serum creatinine, uric acid, albumin, calcium, phosphorus, parathormone, brain natriuretic peptide(BNP) and cardiac troponin I (cTnI).Echocardiography examination was performed on non-dialysis days by an experienced sonographer using a Philips color doppler instrument (CX50). Tissue Doppler methods were used to assess diastolic function of the heart.We measured right ventricular outflow tract, ascending aorta diameter, left atrial diameter, septal thickness, left ventricular posterior wall thickness, left ventricular end-systolic diameter, left ventricular end-diastolic diameter, pulmonary artery diameter, right ventricular diameter, right atrial diameter, left ventricular ejection fraction and others.2; 4. Peak velocity of tricuspid regurgitation > 2.8 m/s [According to the detection methods recommended by the American Echocardiography Association and the European Association of Cardiovascular Imaging in 2016, the following 4 indicators were used to measure the disease:1. Lateral septal e velocity < 7 cm/s, or lateral wall e velocity < 10 cm/s; 2. Average E/e > 14; 3. Left atrial volume index > 34ml/m 2.8 m/s . If two In the meantime, we conducted a questionnaire survey on these patients, it consists of three questions:the symptoms of chest tightness, chest pain, shortness of breath after activity recorded in the past 3 months. The questionnaire was filled out at the same time when the patient underwent the echocardiography. Two hemodialysis specialist nurses conducted the questionnaire beside the patients while the echocardiography was completed. Even if it is missed sometimes, it will be filled in 1–2 days later.All patients signed an informed consent form before the echocardiography examination.p < 0.05 was considered statistically significant.SPSS statistical software was used for analysis in the study. The measured data conforming to normal distribution were expressed as mean ± standard deviation, and comparison between groups was performed by t-test. The measured data of non-normal distribution were represented as M , and comparison between two groups was performed by rank sum test. The adoption rate or percentage of enumeration data was expressed, and comparison between groups was performed by chi-square test. Binary Logsitic regression analysis was used to screen the risk factors for LVDD. The results were expressed as odds ratio (OR), and p<0.05). The serum BNP and cTnI levels were higher (p<0.05), and the triglyceride levels were lower (p = 0.043) in patients of LVDD group. Furthermore, the proportion of LVDD group combined with coronary heart disease increased, and the symptoms of chest tightness and shortness of breath more likely occurred in LVDD patients Table .2.<40 years old), middle-aged group (40–60 years old) and elderly group (> 60 years old). As shown in Table p = 0.002)  Table .3.p < 0.05). Meanwhile, the proportion of left ventricular hypertrophy, left heart enlargement, systolic dysfunction, valve regurgitation, valve stenosis, pulmonary hypertension and pericardial effusion increased significantly (p < 0.05), and the ejection fraction of LVDD group was lower than that of non-LVDD group (p = 0.001).Comparison of echocardiographic parameters between the two groups. As shown in Table 4. Risk factors analysis for LVDD in MHD patients. Logistic regression analysis showed that age, coronary heart disease, left ventricular hypertrophy, recent chest tightness and shortness of breath were significantly associated with diastolic dysfunction in MHD patients, as shown in Table Cardiovascular disease is the most common cause of death in MHD patients . LVDD isp<0.05). Multivariate logistic regression also showed that age was an independent risk factor for LVDD, and the risk of LVDD in the elderly group was 3.86 times higher than that of the young group (95%CI 1.429–10.429). The growth of the age is also an important risk factor for cardiovascular disease. With the increase of age, the formation of reactive oxygen species increases, and mitochondria fusion/fission imbalances, such as continuous myocardial cell stress, causes irreversible damage to the myocardial cells. Meanwhile, vascular wall stiffness, left ventricular wall thickness and fibrosis increase with age, which are the pathophysiological basis for cardiac structural changes and electrophysiological dysfunction [p < 0.05), while the LVDD group had a lower ejection fraction (p = 0.001).Previous studies have shown that increasing age is significantly associated with the development of diastolic dysfunction . The prefunction . In thisfunction . LVH is function . CKD-relfunction . In addifunction . These cfunction . LVDD isfunction . In thisSince the diastolic dysfunction may last for years before any symptoms appear and it may represent the first stage of diastolic heart failure, it is important to find diastolic dysfunction early and start treatment before irreversible structural changes and systolic dysfunction occurring . PreviouThis study was limited by its cross-sectional design, which did not allow causal conclusions to be drawn. And this study did not include long-term follow-up of LVDD patients to further examine the risk of cardiovascular events and all-cause death in MDH patients. In addition, LVDD was not graded in the analysis of diastolic dysfunction. In future studies, prospective stratified studies of LVDD patients are needed to explore treatment methods to improve diastolic dysfunction.LVDD is a common complication in MHD patients, but the increased risk of death is easily ignored. Age and left ventricular hypertrophy are independent risk factors for LVDD in MHD patients. Early detection and intervention of LVDD may be beneficial to reduce the incidence of cardiovascular events.