Characterization of Cardiopulmonary Interactions and Exploring Their Prognostic Value in Acute Bronchiolitis: A Prospective Cardiopulmonary Ultrasound Study

We aimed to delineate cardiopulmonary interactions in acute bronchiolitis and to evaluate the capacity of a combined cardiopulmonary ultrasonography to predict the need for respiratory support. This was a prospective observational single-center study that includes infants <12 month of age admitted to a hospital due to acute bronchiolitis. All the included patients underwent clinical, laboratory and cardiopulmonary ultrasonographic evaluation at the same time point within 24 h of hospital admission. The existence of significant correlation between cardiac and respiratory parameters was the primary outcome. The association of different cardiopulmonary variables with the need of respiratory support higher than O2, the length of stay hospitalization, the PICU stay and the duration of respiratory support were a secondary outcome. We enrolled 112 infants (median age 1 (0.5–3) months; 62% males) hospitalized with acute bronchiolitis. Increased values of the pulmonary variables (BROSJOD score, pCO2 and LUS) showed moderate correlations with NT-proBNP and all echocardiographic parameters indicative of pulmonary hypertension and myocardial dysfunction (Tei index). Up to 36 (32%) infants required respiratory support during the hospitalization. This group presented with higher lung ultrasound score (p < 0.001) and increased values of NT-proBNP (p < 0.001), the Tei index (p < 0.001) and pulmonary artery pressures (p < 0.001). All the analyzed respiratory and cardiac variables showed moderate-to-strong correlations with the LOS of hospitalization and the time of respiratory support. Lung ultrasound and echocardiography showed a moderate-to-strong predictive accuracy for the need of respiratory support in the ROC analysis, with the AUC varying from 0.74 to 0.87. Those cases of bronchiolitis with a worse pulmonary status presented with a more impaired cardiac status. Cardiopulmonary ultrasonography could be a useful tool to easily identify high-risk populations for complicated acute bronchiolitis hospitalization.

Central and Peripheral Cannulation for Cardiopulmonary Bypass in Fetal Sheep: A Comparative Study

Objective:In-utero correction is an option for treatment of critical congenital heart diseases (CHDs). Fetal cardiac surgery for CHDs is dependent on the reliable use of fetal cardiopulmonary bypass (CPB), but this technology remains experimental. In this study, we established fetal CPB models with central and peripheral cannulation to explore the differences between the two cannulation strategies.Methods: Ten fetal sheep with 90–110 gestational days were randomized into central cannulation (n = 5) and peripheral cannulation (n = 5) groups. All fetal CPB models were successfully established. At each time point (0, 30, and 60 min after initiation of CPB), echocardiography was performed. Blood samples were also collected for blood gas analysis and tests of myocardial enzymes and liver and kidney function.Results: In the central cannulation group, right ventricular Tei index significantly increased (p = 0.016) over time. Compared with the peripheral cannulation group, the left ventricular Tei index of the central cannulation group was significantly higher (1.96 ± 0.31 vs. 0.45 ± 0.19, respectively; p = 0.028) and the stroke volume was lower (0.46 ± 0.55 vs. 2.13 ± 0.05, respectively; p = 0.008) at 60 min after CPB. Levels of liver and kidney injury markers and of acid-base balance, including alanine aminotransferase (ALT), aspartate aminotransferase/ALT ratio, blood urea nitrogen (BUN), BUN/creatinine ratio, base excess and bicarbonates, were significantly higher for peripheral than for central cannulation. Other important physiologic parameters, including heart rate, blood pressure, myocardial enzymes, umbilical artery beat index and resistance index, left ventricular Tei index, and left and right ventricular stroke volume, were comparable between the two groups.Conclusions: Both central and peripheral cannulations can be used to establish fetal CPB models. Central cannulation causes more adverse impacts for cardiac function, whereas peripheral cannulation is more susceptible to complications related to inadequate organ perfusion.

Novel Approach to Assess Cardiac Function Using Systolic Performance and Myocardial Performance Indices From Simultaneous Electrocardiography and Phonocardiography Recordings in Dogs With Various Stages of Myxomatous Mitral Valve Disease

Background and Objective: Myxomatous mitral valve disease (MMVD) progression entails changes in the structural and functional properties of the heart affecting cardiac timings and intervals within the cardiac cycle. Conventionally, echocardiography is used to determine the cardiac time intervals (CTIs) including systolic and myocardial performance indices (SPI and MPI) in evaluating cardiac function. Alternatively, these CTIs can also be measured using simultaneous recordings of electrocardiography (ECG) and phonocardiography (PCG), but their values in different MMVD stages remain to be established. This study aimed to establish and prove the use of derived SPI and MPI from a dedicated device as a novel approach to assess cardiac function in different stages of MMVD dogs.Materials and Methods: A prospective study in 52 dogs with different MMVD stages measured the CTIs using a novel device. These were compared and correlated with standard echocardiographic parameters. The predictive value of SPI and three new proposed formulas to estimate MPI (i.e., F1, F2, and F3) in association with asymptomatic from symptomatic MMVD dogs were investigated.Results: Our findings revealed that CTI parameters measured from a novel device including QS1, QS2, S1S2, MPI-F1, and MPI-F2 were altered at different stages of MMVD. The SPI and all proposed MPI formulas were comparable with the systolic time interval and Tei index from echocardiography. In addition, the SPI, MPI-F1, and MPI-F2 were significantly correlated with the Tei index. However, the SPI was not able to differentiate the various stages of MMVD. Conversely, only the MPI-F1 (i.e., (QS1 + S2)/S1S2) demonstrated good predictive accuracy when compared between asymptomatic and symptomatic MMVD dogs similar to the Tei index. Moreover, this formula was able to differentiate stages B1 and C with remarkable predictive accuracy, higher sensitivity, and high specificity when compared with the Tei index.Conclusion: We have successfully described the CTI parameters in different MMVD stages using simultaneous ECG and PCG recordings in dogs. Furthermore, we have proven that the concept of using the newly proposed parameters from a novel device is equivalent to the Tei index. Thus, we established a novel approach to evaluate cardiac function and its supportive use in the diagnosis of MMVD patients.

Echocardiographic predictors of low risk haemodynamic parameters in patients with pulmonary arterial hypertension

Background A periodic and multiparametric assessment of the risk profile of patients with pulmonary arterial hypertension (PAH) is essential for a low-risk oriented treatment strategy. Haemodynamic parameters anyway cannot be collected at each scheduled outpatients clinic follow-up visit. Purpose To evaluate echocardiographic predictors of haemodynamic low-risk parameters in patients with PAH. Methods Patients with PAH referred to our centre were included up to 31 December 2019. All patients underwent baseline demographic, clinical, WHO functional class, 6-minute walk test, brain natriuretic peptide (BNP), right cardiac catheterization and echocardiographic evaluation. Through a multivariate logistic regression analysis we evaluate the echocardiographic predictors of low risk for: 1) BNP/right atrial pressure (RAP): NT-proBNP &lt;300 ng/l/BNP &lt;50 ng/l AND RAP &lt;8 mmHg; 2) cardiac index (CI)/mixed venous oxygen saturation (SvO2): CI ≥2.5 l/min/m2 AND SvO2 &gt;65%. Echocardiographic parameters cut-offs were chosen on the basis of the ROC curves or Literature data. Results 1020 patients were included. The two analysis were performed independently. 1. Independent echocardiographic predictors of low-risk BNP/RAP were: indexed right atrial area, mitral E/A ratio, dimension and inspiratory collapse of inferior vena cava and indexed left ventricular diastolic volume. We elaborated a score utilizing these parameter cut-offs: an indexed right atrial area of 10.4–15 cm2/m2, a mitral E/A ratio of 0.8, dimension and inspiratory collapse of inferior vena cava indicative of 0–5 vs 5–10 vs 10–20 mmHg and an indexed left ventricular diastolic volume of 32 ml/m2. The score has AUC: 0.62, specificity: 92%, sensitivity: 33%, negative predictive value: 70%, positive predictive value: 69%. 2. Independent echocardiographic predictors of low-risk CI/SvO2 were: S wave at TDI, Tei index, tricuspid annular plane systolic excursion (TAPSE), indexed left ventricular diastolic volume and the severity of the tricuspid regurgitation. We elaborated a score utilizing these parameter cut-offs: an S wave at TDI of 9.5 cm/s, a Tei index of 0.4, a TAPSE of 1.7 cm, an indexed left ventricular diastolic volume of 32 ml/m2 and a mild vs more than mild tricuspid regurgitation. The score has AUC: 0.70, specificity: 89%, sensitivity: 50%, negative predictive value: 71%, positive predictive value: 77%. Conclusion Echocardiographic parameters can be used to rule out the presence of low-risk BNP/RAP values (indexed right atrial area, mitral E/A ratio, dimension and inspiratory collapse of inferior vena cava and indexed left ventricular diastolic volume) and low-risk CI/SvO2 (S wave at TDI, Tei index, TAPSE, indexed left ventricular diastolic volume and severity of tricuspid regurgitation). FUNDunding Acknowledgement Type of funding sources: None.

Fetal Hemodynamic Responses to Arterial Occlusion of Acardiac Twins

The objective of this study was to comprehensively assess fetal hemodynamic adaptions to occlusive procedures. Twin pregnancies complicated with acardiac twin and hydrops fetalis of the pump twin were recruited. The occlusive procedures — either alcoholization, radiofrequency ablation, coil embolization or occlusive glue — were performed under ultrasound guidance. Various hemodynamic parameters were assessed before, shortly after, then every 6 h for 48 h and 2−4 weeks after the procedures. Seven pregnancies were recruited. The median (range) gestational age of intervention was 21 (17−26) weeks of gestation. Before the procedures, all cases showed normal cardiac function. Just after the procedures, all cases showed an increase in Tei index and isovolumic relaxation time but returned to preocclusion levels within 6−48 h, except for two cases that were persistently high. Increased preload and poor shortening fraction were observed in two cases, leading to heart failure, with one recovery and one death in utero. Five out of the seven cases got through the critical period with a gradual return to normal hemodynamics, ending with the disappearance of hydrops and successful outcomes. It was concluded that the occlusive procedure could aggravate the overworked heart, leading to heart failure. Preocclusion preload index and Tei index may predict risk of heart failure due to the occlusion. This small series strongly suggests that the occlusion should be performed before the deterioration of cardiac function.

4D imaging of fetal right ventricle—feasibility study and a review of the literature

Functional analysis of the fetal cardiovascular system is crucial for the assessment of fetal condition. Evaluation of the right ventricle with standard 2D echocardiography is challenging due to its complex geometry and irregular muscle fibers arrangement. Software package TOMTEC 4D RV-Function is an analysis tool which allows assessment of right ventricular function based on volumetric measurements and myocardial deformation. The aim of this study was to determine the feasibility of this method in fetal echocardiography. The retrospective study was conducted in the high-flow Referral Center for Fetal Cardiology. We recorded 4D echocardiographic sequences of 46 fetuses with normal hearts. Following parameters were calculated: end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and ejection fraction (EF), right ventricle longitudinal free-wall (RVLS free-wall) and septal strain (RVLS septum). Tei index was calculated as a standard measure or RV function for comparison. 4D assessment was feasible in 38 out of 46 fetuses (83%). RV volumetric parameters—EDV, ESV and SV—increased exponentially with gestational age. Functional parameters—RV Tei index, EF and strains—were independent of gestational age. Mean EF was 45.2% (± 6%), RV free-wall strain was − 21.2% and RV septal strain was − 21.5%. There was a statistically significant correlation between septal and free-wall strains (r = 0.51, p = 0.001) as well as between EF and RV free-wall strain (r = − 0.41, p = 0.011). 4D RV assessment is feasible in most fetuses. Its clinical application should be further investigated in larger prospective studies.

Evaluation of the changes in Tei-index (myocardial performance index) in Doppler echocardiography before and after treating with anthracycline combinations in children with malignancy

Background: Cardiomyopathy usually causes a cardiac dysfunction resistant to treatment due to anthracycline. This study aimed to evaluate the changes in Tei-Index (myocardial performance index) in patients with malignancies treated with anthracycline. Material and Methods: This case-control study was done on 15 children who were treated with low-dose anthracycline (1-199mg/kg) called group A and 15 children who were treated with high dose (>200mg/kg) anthracycline called group B after acquiring consent from their parents. Children with no abnormality in Echo-Doppler results were included in this study. The patients’ age range between 1- 17 years with a mean age of 6.57 years. Another group of healthy children were assigned to group C as a control group who had not received chemotherapy. The first echo was performed right before the treatment and the second one, two weeks after completing chemotherapy. Data were analyzed by the SPSS statistical software. Results: Changes in mean Tei-index in group A were 0.36 ± 0.04 before treatment and 0.43 ± 0.11 after treatment. Changes in mean Tei-index in group B were 0.37 ± 0.04 before treatment and 0.45 ± 0.06 after treatment. There was no significant difference between the two groups using the independent T-test. (p-value= 0.57). No significant correlation between the changes in mean ejection fraction (EF) and treatment was found in the three groups (p-value=0.45). Conclusion: This study showed a change in the Tei-index (MPI) in patients receiving anthracycline; regardless of the dosage, they got in their regimen. Given the use of anthracycline, any abnormal cardiac finding can alert the physicians to the possibility of cardiomyopathy, hence scheduling routine follow-ups are necessary.

A Novel Method for Measuring Myocardial Performance Index using Non-contact Ballistocardiogram System

Aim: The aim was to validate the Systolic Time Intervals (STI) measured by Ballistocardiography (BCG) with STI derived from simultaneously performed Transthoracic Echocardiogram (TTE) and attempt to create an AI algorithm that automatically calculates Tei Index from BCG tracings. Study design: Cross-sectional study. Place and Duration of Study: Department of Cardiology and Department of Electrophysiology of Sri Jayadeva Institute of Cardiovascular Sciences & Research, Bangalore, India, between January 2020 and January 2021. Methodology: Two hundred seventy-four patients with clinically indicated TTE were enrolled in the study, average age was 52. Simultaneous recordings on BCG and TTE were done. 150 patients had clinically usable TTE images for accurate calculations. STI was calculated independently by operators experienced in TTE and BCG. Results were compared using Pearson’s R. A proprietary AI algorithm for automatically calculating the MPI, was trained over a subset of patients. Its accuracy in detecting STI was compared to that of TTE and manually calculated STI from BCG. Results: There was a strong positive correlation (r=0.766, P<0.00, 99%CI [0.691,0.824]) between the TTE and BCG derived MPI values. The result was validated over predetermined subgroups of subjects with reduced EF (EF<50) and subjects with normal EF (EF>=50). The AI algorithm had correlation of 0.54(p<0.01) with the MPI calculated by TTE and 0.34(P<0.10) with the manually calculated MPI on the BCG. Conclusion: BCG derived manual and automated MPI correlates well with TTE derived MPI in a variety of EF fraction subgroups. Automated calculation algorithms for MPI derived from BCG remain a work under progress.

Deficiency of Ataxia-Telangiectasia Mutated Kinase Modulates Functional and Biochemical Parameters of the Heart in Response to Western-type Diet

Ataxia telangiectasia mutated kinase (ATM) deficiency exacerbates heart dysfunction late after myocardial infarction. Here, we hypothesized that ATM deficiency modulates Western-type diet (WD)-induced cardiac remodeling with an emphasis on functional and biochemical parameters of the heart. Weight gain was assessed in male wild-type (WT) and ATM heterozygous knockout (hKO) mice on weekly basis, while cardiac functional and biochemical parameters were measured 14 weeks post-WD. hKO-WD mice exhibited rapid body weight gain at weeks 5, 6, 7, 8 and 10 vs WT-WD. WD decreased percent fractional shortening and ejection fraction, and increased end systolic volumes and diameters to a similar extent in both genotypes. However, WD decreased stroke volume, cardiac output, peak velocity of early ventricular filling and aortic ejection time, and increased isovolumetric relaxation time (IVRT) and Tei index in vs WT-NC (normal chow). Conversely, IVRT, isovolumetric contraction time and Tei index were lower in hKO-WD vs hKO-NC and WT-WD. Myocyte apoptosis and hypertrophy were higher in hKO-WD vs WT-WD. WD increased fibrosis and expression of Collagen-1α1, MMP-2, and MMP-9 in WT. WD enhanced AMPK activation, while decreasing mTOR activation in Hko. Akt and IKK-α/β activation, and Bax, PARP-1 and Glut-4 expression were higher in WT-WD vs WT-NC, while NFкB activation and Glut-4 expression were lower in hKO-WD vs hKO-NC. Circulating concentrations of IL-12(p70), eotaxin, IFN-γ, MIP-1α and MIP-1β were higher in hKO-WD vs WT-WD. Thus, ATM deficiency accelerates weight gain, induces systolic dysfunction with increased preload, and associates with increased apoptosis, hypertrophy and inflammation in response to WD.

Tei index and anthracycline induced cardiotoxicity: a systematic review

Background: Anthracycline agents are known to be effective treatments for solid tumors and hematological malignancies. Although these agents improve survival, their use is associated with cardiotoxic effects, which most commonly manifests as left ventricular systolic dysfunction (LVSD). As such guidelines recommend the periodic assessment of left ventricular ejection fraction (LVEF). However, as diastolic dysfunction likely proceeds systolic impairment in this setting, the role of Tei index may offer additional benefit in detecting subclinical LVSD. Methods: We conducted a systematic review to investigate the evidence for the use of Tei index in assessing for subclinical cardiotoxicity in patients receiving anticancer agents. A search of Medline and EMBASE was performed and relevant studies were reviewed and narratively synthesized. Results: A total of 13 studies were included with a total of 800 patients (mean age range 46-62 years, percentage of male participants ranged from 0%-86.9%). An increase in Tei index was observed in 11 studies, which suggesting a decline in cardiac function following chemotherapy. Out of these, 6 studies indicated that the Tei index is a useful parameter in predicting cardiotoxic LVSD. Furthermore, 5 studies indicated Tei index to be superior to LVEF in detecting subclinical cardiotoxicity. Conclusions: While there are some studies that suggest that Tei index may be a useful indicator in assessing for subclinical anthracycline related cardiotoxicity, the findings are inconsistent so more studies are needed before the evaluation of Tei index should be performed routinely in patients receiving chemotherapy.