Systolic Left Ventricular Research Articles

Right ventricular energetic biomarkers from 4D Flow CMR are associated with exertional capacity in pulmonary arterial hypertension

BackgroundCardiovascular magnetic resonance (CMR) offers comprehensive right ventricular (RV) evaluation in pulmonary arterial hypertension (PAH). Emerging four-dimensional (4D) flow CMR allows visualization and quantification of intracardiac flow components and calculation of phasic blood kinetic energy (KE) parameters but it is unknown whether these parameters are associated with cardiopulmonary exercise test (CPET)-assessed exercise capacity, which is a surrogate measure of survival in PAH. We compared 4D flow CMR parameters in PAH with healthy controls, and investigated the association of these parameters with RV remodelling, RV functional and CPET outcomes.MethodsPAH patients and healthy controls from two centers were prospectively enrolled to undergo on-site cine and 4D flow CMR, and CPET within one week. RV remodelling index was calculated as the ratio of RV to left ventricular (LV) end-diastolic volumes (EDV). Phasic (peak systolic, average systolic, and peak E-wave) LV and RV blood flow KE indexed to EDV (KEIEDV) and ventricular LV and RV flow components (direct flow, retained inflow, delayed ejection flow, and residual volume) were calculated. Oxygen uptake (VO2), carbon dioxide production (VCO2) and minute ventilation (VE) were measured and recorded.Results45 PAH patients (46 ± 11 years; 7 M) and 51 healthy subjects (46 ± 14 years; 17 M) with no significant differences in age and gender were analyzed. Compared with healthy controls, PAH had significantly lower median RV direct flow, RV delayed ejection flow, RV peak E-wave KEIEDV, peak VO2, and percentage (%) predicted peak VO2, while significantly higher median RV residual volume and VE/VCO2 slope. RV direct flow and RV residual volume were significantly associated with RV remodelling, function, peak VO2, % predicted peak VO2 and VE/VCO2 slope (all P < 0.01). Multiple linear regression analyses showed RV direct flow to be an independent marker of RV function, remodelling and exercise capacity.ConclusionIn this 4D flow CMR and CPET study, RV direct flow provided incremental value over RVEF for discriminating adverse RV remodelling, impaired exercise capacity, and PAH with intermediate and high risk based on risk score. These data suggest that CMR with 4D flow CMR can provide comprehensive assessment of PAH severity, and may be used to monitor disease progression and therapeutic response.Trial registration number: https://www.clinicaltrials.gov. Unique identifier: NCT03217240.

Chamber sizes and left ventricular mass in sub-Saharan Africans: Normal echocardiographic values from the TAHES study

Reported ranges of normal echocardiographic values for chambers size or left ventricular (LV) mass are mostly issued from Caucasian cohorts and they may not be representative of diverse world population. Our study aimed to establish reference values in a community-dwelling Beninese population cohort. This study is a part of TAHES, a population-based prospective cohort study initiated in 2015 in Benin. Overall transthoracic echocardiography examinations were performed by 4 cardiologist, and analyzed off-line by a single observer. Interventricular septal (IVSWT), posterior wall thicknesses (PWT) and LV internal diameters were measured from the parasternal long-axis acoustic window in M mode. The LV mass was calculated from linear measurements obtained from parasternal views. LV, left atrial (LA) and right atrial (RA) volumes were measured using the discs’ summation method. Normal limits were defined as the 95th percentiles. We included 513 normotensive individuals (206 men and 307 women, age 40 ± 14 years, BSA 1.59 ± 0.18 m 2 ). End-diastolic IVSWT, LV internal diameter, PWT, and systolic LV internal diameter were respectively 10.4 ± 2.5, 48 ± 5, 9.8 ± 1.9, 15 ± 2.7 mm for men and 9.1 ± 2.4, 45 ± 4.3, 9 ± 1.8, 13.2 ± 2.5 mm for women. LV mass was significantly greater in men (172 ± 53 vs. 135 ± 37 g). Upper limits of LV mass were 260 g for men and 206 g for women. There was a correlation between LV mass and age in both sexes ( r = 0.20, P < 0.0001). The indexed values with the upper limits are summarized in Table 1 . Normal values in West Africa differ from those established in Caucasian populations with greater LV mass, wall thicknesses and LV sizes.

Impact of sacubitril/valsartan on systolic heart failure: Right heart location and clustering analysis.

Heart failure with reduced ejection fraction (HFrEF) is a heterogeneous syndrome. In heart failure (HF) classifications, right ventricle (RV) function was for a long time unrecognized in favor of left ventricular ejection fraction (LVEF). The response to sacubitril/valsartan might differ according to phenotypes and the impact of right ventricular characteristics on this response remains controversial. First, we applied clustering analysis in a HFrEF population undergoing sacubitril/valsartan treatment according to guidelines, to identify phenotypes and their associated clinical outcomes. Secondly, we evaluated RV-remodeling. It is a prospective, observational, single-center study conducted on 108 symptomatic patients (mean age 66 ±12.8 years, 22.2% women). First, the clustering analysis was applied in a HFrEF population undergoing sacubitril/valsartan treatment, according to the guidelines, in order to identify phenotypes and clinical outcomes associated with them. Secondly, we evaluated RV-remodeling. Two distinct clusters were identified. Among the differences between phenotypes, RV (tricuspid annular plane systolic excursion (TAPSE) 16 ±4 mm compared to 19 ±4 mm, p < 0.001; RV free wall strain -19 ±5% compared to -21 ±4%, p = 0.046; RV fraction area change (FAC) 31 ±9% compared to 38 ±9%, p < 0.001), LV-filling pressure (E-wave deceleration time 138 (median: 41) ms compared to 180 (median: 94) ms, p < 0.001; E/e' 16.7 (median: 8.0) ms compared to 13.0 (median: 9.7) ms, p = 0.02) and creatinine level (106 ±34 μmol/L compared to 90 ±19 μmol/L, p = 0.002) were substantially different at the initiation of therapy. Major adverse cardiac events (MACEs) or death occurred in 38 out of 107 patients: 51.1% in cluster 1 compared to 24.2% in cluster 2 (p = 0.0074). A significant improvement in RV-functional parameters was observed under treatment. The TAPSE improved and correlated with the change in left ventricular (LV) function. Yet, it did not correlate with systolic pulmonary artery pressure (sPAP) and LV end-diastolic diameter. The HFrEF phenotype characterized by more severe RV dysfunction has a worse prognosis during sacubitril/valsartan therapy. Both RVand LV functions significantly improve when the patient is treated with sacubitril/valsartan.

NP202 treatment improves left ventricular systolic function and attenuates pathological remodelling following chronic myocardial infarction

AimsMyocardial injury is a major contributor to left ventricular (LV) remodelling activating neurohormonal and inflammatory processes that create an environment of enhanced oxidative stress. This results in geometric and structural alterations leading to reduced LV systolic function. In this study we evaluated the efficacy of NP202, a synthetic flavonol, on cardiac remodelling in a chronic model of myocardial infarction (MI). Main methodsA rat model of chronic MI was induced by permanent surgical ligation of the coronary artery. NP202 treatment was commenced 2 days post-MI for 6 weeks at different doses (1, 10 and 20 mg/kg/day) to determine efficacy. Cardiac function was assessed by echocardiography prior to treatment and at week 6, and pressure-volume measurements were performed prior to tissue collection. Tissues were analysed for changes in fibrotic and inflammatory markers using immunohistochemistry and gene expression analysis. Key findingsRats treated with NP202 demonstrated improved LV systolic function and LV geometry compared to vehicle treated animals. Furthermore, measures of hypertrophy and interstitial fibrosis were attenuated in the non-infarct region of the myocardium with NP202 at the higher dose of 20 mg/kg (P < 0.05). At the tissue level, NP202 reduced monocyte chemoattractant protein-1 expression (P < 0.05) and tended to attenuate active caspase-3 expression to similar levels observed in sham animals (P = 0.075). SignificanceImproved LV function and structural changes observed with NP202 may be mediated through inhibition of inflammatory and apoptotic processes in the MI setting. NP202 could therefore prove a useful addition to standard therapy in patients with post-MI LV dysfunction.

644 Clinical outcomes of patients with end-stage heart failure treated with left ventricular assist devices

Abstract Aims During the last decades left ventricular assist devices (LVAD) have assumed a central role in the management of patients with symptomatic end-stage heart failure (HF). The mortality rate and prognosis of these patients is poor, but the substantial progress in LVAD technologies has led to significant improvements in clinical outcomes. The third generation LVADs are small, centrifugal flow pumps, contained within the pericardium and based on full magnetic levitation, which allow to reduce the risks of pump thrombosis. The aim of our study is to evaluate the clinical outcomes and functional capacity of patients with end-stage HF before and after the implantation of a third generation LVAD, the HeartMate 3™. Methods and results We evaluated eight patients with end-stage HF, followed to Cardiology Unit of Brotzu Hospital in Cagliari and consecutively implanted with the HeartMate 3™ LVAD in the Cardiac Surgery Unit from 12 May 2017 to 24 October 2019. For each patient we collected socio-demographic and clinical features, as well as laboratory tests, therapy, echocardiographic and haemodynamics parameters and any complication. Most of our patients were male (87.5%), with mean age 65.6 ± 5.7 years and higher prevalence of cardiovascular risk factors, like smoke (87.5%), hypertension (62.5%) and hypercholesterolaemia (62.5%). The etiology of HF was mainly due to idiopatic dilated cardiomyopathy (62.5%) and ischaemic heart disease (25%); the only female patient had a history of iatrogenic dilated cardiomyopathy, post-chemo and radiotherapy. Before the implantation most of our patients experienced severe symptoms, recurrent decompensations resulting in NYHA class IV (50%) and III (37.5%); the 100% was inotrope dependant and needed short-term support devices like IABP (75%) and ECMO (25%); the 62.5% underwent mechanical ventilation. The patients had severe left ventricular (LV) dysfunction, with low LV ejection fraction (18.6 ± 1.8%), cardiac output (3.08 ± 1.2 l/min) and cardiac index (1.81 ± 0.83 l/min/m2) and increasing filling pressure (26.5 ± 9.7 mmHg), central venous pression (12.7 ± 5 mmHg) and pulmonary arteries resistance (3.81 ± 1 μW). We also found important LV structural changes, with a severe dilatation and increased volumes (EDV 140.62 ± 67.1 ml/m2; ESV 113.7 ± 55.3 ml/m2). Mild right ventricle dysfunction was present only in 50% of patients with normal diameters. We observed few complications, mainly driveline infections (42.8%) and only one case of in-hospital mortality due to multiple organ failure. The seven patients presenting at FU shown a significant improvement in everyday symptoms and functional capacity compared to pre-operative features (P = 0.029). We also found a mild improvement of systolic LV function compared to pre-operatory values, with increase of CO (3.58 ± 0.65 l/min vs. 3.08 ± 1.2) and EF (21.2 ± 9.4% vs. 18.71 ± 97) even though not statistically significant. Conclusions Our study confirms that patients with end-stage HF are mostly male, older, experience severe symptoms and require frequent hospitalizations. The survival rate reached the 87.5% and remained stable even three years after implantation. On the whole our study showed that LVADs can significally improve clinical outcomes and survival rates, confirming the role as treatment of choice for many patients with end-stage HF who cannot undergo heart transplantation, which still remains the gold standard. The complications related to LVAD were few, thanks to careful patients selection, showing a favourable risk benefit ratio.

Prognostic Implications of Progressive Systemic Ventricular Dysfunction in Congenitally Corrected Transposition of Great Arteries

ObjectivesThe purpose of this study was to determine the risk factors for and prognostic implications of progressive right ventricular systolic dysfunction (RVD) in adults with congenitally corrected transposition of great arteries. BackgroundThere are no effective therapies for RVD; hence the need to identify and modify risk factors for progressive RVD. MethodsRV systolic function was assessed by using RV longitudinal strain (RV-LS). The first echocardiogram (baseline echocardiogram) and all subsequent annual echocardiograms performed within 5 years from the baseline echocardiogram were analyzed. Progressive RVD (temporal decline in RV-LS) was assessed as the average annual change in RV-LS within 5 years of imaging follow-up. ResultsOf 186 patients (mean age 40 ± 12 years), the RV-LS at baseline was –17% ± 4%, and the annual decline in RV-LS was –4% (95% CI: –6 to –2). The risk factors for progressive RVD were left ventricular (LV) systolic dysfunction, LV pacing, and systemic hypertension. Cardiovascular events (heart failure hospitalization, heart transplant, and death) occurred in 57 (27%) patients. Progressive RVD was associated with cardiovascular events, independent of RV systolic function at baseline. In subgroup analyses assessing impact of therapies (medical therapy, cardiac resynchronization therapy, and tricuspid valve replacement), only tricuspid valve replacement was associated with improvement in RV systolic function when performed before onset of RVD. ConclusionsPatients with congenitally corrected transposition of great arteries were at risk for progressive RVD, and the risk factors for progressive RVD were LV pacing, systemic hypertension, and concomitant LV dysfunction. Further studies are required to determine whether strict blood pressure control and early tricuspid valve replacement will prevent progressive RVD.

Wenxin Granules Regulate Endoplasmic Reticulum Stress Unfolded Protein Response and Improve Ventricular Remodeling on Rats with Myocardial Infarction.

Background. Arrhythmia after myocardial infarction is the leading cause of death in clinical heart disease. Increasing studies have shown that the response to endoplasmic reticulum (ER) stress (ERS) caused by myocardial infarction is related to prognosis and the development of arrhythmias. The unfolded protein response (UPR) could serve as an important regulatory signaling pathway following myocardial infarction. The traditional Chinese medicine Wenxin Granules improve arrhythmias following myocardial infarction, which may be related to ERS intervention and the activation of the UPR and apoptosis. We aimed to investigate the involvement of Wenxin Granules in the activation of the UPR and apoptosis following myocardial infarction. Left coronary artery ligation was established as a rat model of myocardial infarction. The rats were randomly divided into the model group, low-dose Wenxin Granule group, high-dose Wenxin Granule group, and metoprolol group. Rats with only wire insertion and no ligature were used as the sham group. Small animal ultrasound systems were used to detect changes in heart structure and function, and the electrical stimulation threshold for ventricular fibrillation was detected. The expression of glucose-regulated protein (GRP)78, activating transcription factor (ATF)6, X-box binding protein (XBP)1, protein kinase–like ER kinase (PERK), phosphorylated (p)-PERK, Bax, Bcl2, C/EBP homologous protein (CHOP), caspase 12, caspase 8, and caspase 3 were detected by western blot, and terminal deoxynucleotidyl transferase dUTP Nick end labeling (TUNEL) was used to determine the cardiomyocyte apoptosis index. Compared with the sham group, rats in the model group displayed immediate ST-segment elevation and pathological Q waves after 24 hours. After 2 weeks, the left ventricular (LV) anterior wall thickness (LVAW) became thinner, and the inner diameter (LVID) increased. The end-diastolic LVAW (LVAWd), end-systolic LVAW (LVAWs), ejection fraction (EF), and fractional shortening (FS) were significantly reduced (P < 0.01), whereas the LVIDd, LVIDs, diastolic LV volume (LV Vold), and systolic LV volume (LV Vols) significantly increased (P < 0.01). The ventricular fibrillation threshold decreased significantly (P < 0.01). ERS proteins GRP78, p-PERK, PERK, ATF6, and XBP1 and apoptotic proteins CHOP, Bax, caspase 12, caspase 8, and caspase 3 significantly increased (P < 0.01, P < 0.05), whereas Bcl-2 expression and the Bcl-2/Bax ratio decreased (P < 0.01). Compared with the sham group, LVAWd, LVAWs, FS, and Bcl-2 protein expression were significantly increased in the low-dose Wenxin Granule group (P < 0.01, P < 0.05), and p-PERK and ATF6 decreased (P < 0.01, P < 0.05). Compared with the sham group, LVAWd, LVAWs, EF, FS, and the ventricular fibrillation threshold significantly increased in the high-dose Wenxin Granule and metoprolol groups (P < 0.01, P < 0.05), whereas LVIDs, LV Vols, and ERS proteins were significantly decreased (P < 0.01, P < 0.05). CHOP, Bax, caspase 12, caspase 8, and caspase 3 protein expression decreased in the Wenxin Granule group (P < 0.01, P < 0.05), whereas Bcl-2 and the Bcl-2/Bax ratio increased (P < 0.01, P < 0.05). LVIDd and Bax decreased in the metoprolol group (P < 0.01, P < 0.05), and the Bcl-2/Bax ratio increased (P < 0.05). The cardiomyocyte apoptosis index values for the low- and high-dose Wenxin Granule and metoprolol groups were significantly reduced (P < 0.05). This study suggested that the UPR is an essential mechanism underlying pathological injury after myocardial infarction. Wenxin Granule treatment can improve ventricular remodeling and cardiac function and inhibit arrhythmia by preventing excessive ERS from activating the UPR and apoptosis.

Determinants of left ventricular structure, filling and long axis function in systemic sclerosis.

Abnormalities of left ventricular (LV) structure, filling and long-axis function have all been reported in subjects with systemic sclerosis (SSc) and a normal LV ejection fraction (EF), but previous study findings have not been consistent. The aim of this study was to identify factors which could have confounded the analyses in previous studies of SSc, and in particular to consider the variables of body surface area (BSA), sex, age, heart rate, blood pressure (BP), disease duration (DD), disease type (limited versus diffuse) and interstitial lung disease (ILD). Echocardiography was performed on 100 subjects with SSc (79 women; age 56±15 years) with a LVEF ≥50% and free of pulmonary arterial hypertension, coronary artery disease, more than mild valvular heart disease and atrial fibrillation. Measurements were performed of the LV end-diastolic dimension (LVEDD) and septal wall thickness (SWT), the transmitral Doppler E, A and deceleration time (DT), and the peak systolic (s') and early diastolic (e') LV long-axis velocities. Multivariate analyses were performed to investigate correlations of the above LV variables with BSA, sex, age, heart rate, BP, DD, disease type, and the presence of ILD. DD varied between 0.1 and 41.2 years, 25% had diffuse and 75% had limited disease, and 37% had ILD. SWT and LVEDD were positively correlated with BSA, SWT was also positively correlated with age and larger in males, and LVEDD was larger in diffuse disease. Age was positively correlated with A and DT, and inversely correlated with E and E/A, and heart rate was inversely correlated with E and E/A. None of E, A, E/A, or DT were independently associated with DD or disease type. Septal and lateral LV wall s' and e' were all inversely correlated with age, and there was a small independent contribution to the prediction of lateral s' from DD, but no association of either s' or e' with disease type. The presence of ILD was not a predictor of any of the LV variables. In SSc there are associations of sex, body size, age and disease type with LV structural variables, of age and heart rate with E/A, and of age with both systolic and early diastolic LV long-axis velocities. Appropriate adjustment for these variables could help to resolve current uncertainties regarding SSc effects on the left ventricle.

Phenotyping heart failure using model-based analysis and physiology-informed machine learning.

To phenotype mechanistic differences between heart failure with reduced (HFrEF) and preserved (HFpEF) ejection fraction, a closed-loop model of the cardiovascular system coupled with patient-specific transthoracic echocardiography (TTE) and right heart catheterization (RHC) data was used to identify key parameters representing haemodynamics. Thirty-one patient records (10 HFrEF, 21 HFpEF) were obtained from the Cardiovascular Health Improvement Project database at the University of Michigan. Model simulations were tuned to match RHC and TTE pressure, volume, and cardiac output measurements in each patient. The underlying physiological model parameters were plotted against model-based norms and compared between HFrEF and HFpEF. Our results confirm the main mechanistic parameter driving HFrEF is reduced left ventricular (LV) contractility, whereas HFpEF exhibits a heterogeneous phenotype. Conducting principal component analysis, -means clustering, and hierarchical clustering on the optimized parameters reveal (i) a group of HFrEF-like HFpEF patients (HFpEF1), (ii) a classic HFpEF group (HFpEF2), and (iii) a group of HFpEF patients that do not consistently cluster (NCC). These subgroups cannot be distinguished from the clinical data alone. Increased LV active contractility ( ) and LV passive stiffness ( ) at rest are observed when comparing HFpEF2 to HFpEF1. Analysing the clinical data of each subgroup reveals that elevated systolic and diastolic LV volumes seen in both HFrEF and HFpEF1 may be used as a biomarker to identify HFrEF-like HFpEF patients. These results suggest that modelling of the cardiovascular system and optimizing to standard clinical data can designate subgroups of HFpEF as separate phenotypes, possibly elucidating patient-specific treatment strategies. KEY POINTS: Analysis of data from right heart catheterization (RHC) and transthoracic echocardiography (TTE) of heart failure (HF) patients using a closed-loop model of the cardiovascular system identifies key parameters representing haemodynamic cardiovascular function in patients with heart failure with reduced and preserved ejection fraction (HFrEF and HFpEF). Analysing optimized parameters representing cardiovascular function using machine learning shows mechanistic differences between HFpEF groups that are not seen analysing clinical data alone. HFpEF groups presented here can be subdivided into three subgroups: HFpEF1 described as 'HFrEF-like HFpEF', HFpEF2 as 'classic HFpEF', and a third group of HFpEF patients that do not consistently cluster. Focusing purely on cardiac function consistently captures the underlying dysfunction in HFrEF, whereas HFpEF is better characterized by dysfunction in the entire cardiovascular system. Our methodology reveals that elevated left ventricular systolic and diastolic volumes are potential biomarkers for identifying HFrEF-like HFpEF patients.

High level of growth differentiation factor 15 and lower left ventricular ejection fraction as predictors of left atrial thrombosis in patients with nonvalvular atrial fibrillation

Abstract Background The presence of left atrial/left atrial appendage (LA/LAA) thrombus is used as a surrogate marker of potential stroke in patients (pts) with atrial fibrillation (AF). Purpose To assess the role of growth differentiation factor 15 (GDF-15) level, clinical and echocardiographic (EchoCG) data as predictors of LA/LAA thrombus in pts with nonvalvular AF. Methods Out of 158 pts with nonvalvular AF admitted to Cardiology Center for radiofrequency ablation or elective cardioversion in 2019–2020 2 groups were formed according to transesophageal EchoCG results: group 1 included pts without LA/LAA thrombus (n=102, mean age 59.5±6.0 years) and group 2 (n=42, mean age 60.9±8.8 years) – pts with LA/LAA thrombus. Arterial hypertension was found in 93 pts of group 1 (91%) and in 40 pts of group 2 (95%, p=0.42), coronary artery disease - in 53 pts (52%) and 29 pts (69%), respectively (p=0.06). Both groups did not differ in frequency and spectrum of oral anticoagulants administration. General clinical assessment, EchoCG, and laboratory tests were performed, including GDF-15 (pg/ml) levels using Human GDF-15/MIC-1 ELISA kit and NT-proBNP (pg/ml) in blood. Results Pts with LA/LAA thrombus more often had persistent AF, while paroxysmal AF was more common in pts without thrombus. There was a tendency to more significant congestive heart failure in group 2. Mean CHA2DS2-VASc score was higher in pts with LA/LAA thrombus, also there was a tendency to a larger proportion of pts with scores ≥3. According to EchoCG data, sizes and volumes of both atria, right ventricle, end-systolic volume, left ventricular (LV) size, pulmonary artery systolic pressure and LV mass index were higher in group 2; LV ejection fraction (LVEF) was normal in both groups, but it was significantly lower in pts with LA/LAA thrombus: 59.1±5.1 and 64.0±7.3, respectively (p&amp;lt;0.001). GDF-15 and NT-proBNP levels were significantly higher in group 2 compared to group 1: p=0.00025 and p=0.ehab724.048801 respectively. According to ROC analysis cut-off were set at level &amp;gt;935.0 pg/ml for GDF-15 (AUC=0.705, 95% CI 0.609–0.800, p&amp;lt;0.001) and &amp;gt;143 pg/ml for NT-proBNP (AUC=0.759, 95% CI 0.670–0.849, p&amp;lt;0.001). Multivariate logistic regression revealed the following variables as independent predictors of LAAT: GDF-15 &amp;gt;935.0 pg/ml (OR=4.132, 95% CI 1.305–13.084) and LVEF (OR=0.859, 95% CI 0.776–0.951). According to ROC analysis, the model had a good quality: AUC=0.776 (p&amp;lt;0.001), sensitivity was 78.3%., specificity - 78.3%. Conclusion High level of GDF-15 (&amp;gt;935.0 pg/ml) along with lower LVEF are independent predictors of LA/LAA thrombus in pts with nonvalvular AF. Funding Acknowledgement Type of funding sources: None.

The impact of left atrial strain parameters on systolic and diastolic improvement following TAVI

Abstract Introduction Transcatheter aortic valve implantation (TAVI) can improve left ventricular (LV) mechanics and has been shown to improve long term survival. Data on the prognostic value of left atrial (LA) strain following TAVI are scarce. LA strain – a surrogate of LV filling pressure - can aid the early detection of diastolic dysfunction and correlates with the extent of fibrosis in atrial remodelling. Purpose In this multimodality study, we aimed to evaluate the prognostic value of LA function measured before hospital discharge following TAVI and to further elucidate its association with LV and LA reverse remodelling. Methods In this prospective single center study, we investigated 90 patients (mean age 78.5 years, 46.7% female) with severe, symptomatic aortic stenosis (AS) who underwent transthoracic echocardiography immediately after TAVI and 6 months later. LA and LV global longitudinal strain parameters were obtained by speckle tracking echocardiography. CT angiography (CTA) was performed for pre-TAVI planning and repeated at 6 months follow-up. LV mass values were derived from the serial CTA images. We defined LV reverse remodelling as reduction of myocardial mass quantified on CTA and as an improvement of LV global longitudinal strain (GLS). LA reverse remodelling was assessed based on the peak reservoir strain values (LAGS). The association of LA and LV global strain parameters, LA stiffness, systolic and diastolic functional parameters and LV mass based reverse remodelling were analysed using Pearson correlation coefficient and linear regression models. Results The mean LAGS and LVGLS values were 17.7% and 15.3% at discharge and 20.2% and 16.6% at follow-up, respectively (p=0.024, p&amp;lt;0.001). LA and LV strain values improved in 60.6% and 74.5% of all patients. Reduced LAGS (&amp;lt;20%) was found in 66.7% of all patients at baseline. LA strain at discharge correlated significantly with diastolic parameters (E wave, E/e', LAVI, all p&amp;lt;0.05). Atrial reverse remodelling based on LAGS change correlated with LVGLS change (p&amp;lt;0.01, standardized β=0.53) and LAGS at discharge (p=0.012, standardized β=−0.30). LAGS correlated with the extent of morphological LV remodelling based on LV mass reduction (p=0.002, coeff: 0.36). Elevated LA stiffness at discharge (upper tercile) leads to substantially lower LAGS at 6 months versus patients with lower LA stiffness value (1. and 2. tercile): 16.4±10.0 vs 21.9±9.8, p=0.042. Conclusion Patients with reduced LAGS immediately after TAVI showed a larger extent of LV reverse remodelling during follow up. On the other hand, increased LA stiffness at discharge was consistent with irreversible LA damage as demonstrated by a lack of improvement in LA function. Funding Acknowledgement Type of funding sources: None.

Echocardiographic parameters of myocardial work in relation to prolonged strenuous physical exercise

Abstract Background Myocardial work (MW) assessed by echocardiography is a novel measure of left ventricular (LV) function. This measure is load-independent, and therefore a more accurate method for assessing LV function when there are changes in loading conditions. The purpose of this study was to examine alterations in MW parameters, blood pressure (BP) and LV global longitudinal strain (LV GLS) in relation to strenuous exercise, and to compare the response between two different physical stress situations. Methods 59 healthy recreational athletes were assessed by echocardiography before-, immediately- and 24 hours after two episodes of high-intensity endurance exercise. The first exercise was a cardiopulmonary exercise (CPX) test, which included both a stepwise lactate threshold- and a maximal oxygen uptake test. The second exercise was a 91-km mountain bike leisure sport cycling competition. Global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE) were estimated from LV pressure-strain loops, constructed from a combination of LV GLS and non-invasive BP, using commercially available software package (Echopac V.202, GE). Results Subjects were 52 (43–59) years old (73% men). The duration of the CPX-test was 43 (40–45) minutes, and the race was 230 (210–245) minutes. The average heart rate during the CPX-test and the race was 144 (140–153) and 154 (148–161) beats per minute (bpm), respectively. The relative changes (percent) in systolic blood pressure (SBP) and LV GLS compared with pre-exercise values are demonstrated in Figure 1a, and GWI and GCW compared with pre-exercise values in Figure 1b. GWI at baseline was 2156 (1899–2400) mmHg% and GCW 2383 (2152–2668) mmHg%. There was a significant reduction in LV GLS (p=0.015), SBP, GWI and GCW following the CPX-test and the race (p&amp;lt;0.001), while there was an increase in heart rate and cardiac output (p&amp;lt;0.001). After the race, there was a significant (p=0.001) increase in GWW, and a reduction (p=0.006) in GWE. Conclusion There was a significant reduction in GWI and GCW after both the CPX-test and the race, suggesting that these markers reflect increased myocardial exhaustion following strenuous physical exercise. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by ConocoPhillips and the Simon Fougner Hartmann Trust Figure 1aFigure 1b

A 3D-TTE left atrial function study in cardio-oncology patients

Abstract Introduction Transthoracic Doppler echocardiography (TTE) remains the standard imaging method to evaluate cancer therapeutics-related cardiac dysfunction (CTRCD). 3D-TTE with strain analysis is a novel technique, proved useful for earlier detection of left ventricular (LV) function impairment. However, diastolic and left atrial (LA) function impact is less studied. Purpose To assess LA volumetric and LA strain (LAS) features by 3D-TTE in cardio-oncology patients. Methods A prospective study of female breast cancer patients (P) submitted to therapy (TH) who underwent serial monitoring by 2D and 3D-TTE. Standard 2D, 3D-TTE and LAS parameters were evaluated, including longitudinal (LALS) and circumferential strain (LACS) during conduit (cd), contraction (ct) and reservoir (r) phases. P were evaluated at T0, T1 and T2 (before, ≥6 and ≥12 months after starting TH). CTRCD was defined as an absolute decrease in 2D LVEF &amp;gt;10% to a value &amp;lt;54% or a relative decrease in 2D GLS &amp;gt;15%, according to literature. P with previous cancer treatment, coronary artery disease, significant valvular disease, and atrial arrhythmias were excluded. Results 98 P (mean age 54.6±12.0 years-old), mostly treated with anthracyclines (78.6%, cumulative dose 268.2±77.6mg/m2), anti-HER (70.4%) and radiotherapy (80.6%) were included. 2D LV and LA volumes had a significantly raise from baseline to T1 (2D LVEDV 82.2±18.8 vs 91.9±18.8 mL, p=0.019 and LA 43.3±12.9 vs 49.8±13.3 mL, p=0.005). 2D and 3D LVEF were significantly reduced during TH, however remaining within the limits of normality. 2D GLS was also impaired at T1 (−19.9±2.6% vs −18.6±3.1%, p=0.009). During a mean follow-up of 14.1±8.1months, 31 P (31.6%) developed CTRCD. 3D LV and LA volumes also globally increased at T1 comparing to baseline with partially recovery at T2. Maximum LA volume was significantly higher at T1 (39.1±9.3 vs 43.6±10.6 ml, p=0.024). 3D LA ejection fraction (T0 53.7±9.7%, T1 53.4±8.6%, T2 49.9±8.6%, pT0-T2=0.039) and LAS values tended to progressively worse during TH. LA dilation (vol&amp;gt;34ml/m2) at baseline was correlated to dysfunction in contraction phase at T1 (LACSct −19.6±8.6 vs −17.3±4.6%, p=0.024). LACSr has substantially decreased from baseline to T2 (31.4±11.6 vs 27.0±10.4%, p=0.05). In univariate analysis, delta LALSr (T1-T0) was a predictor of CTRCD (mean −5.2% vs 1.9%, p=0.05). Conclusion CTRCD was frequent during the earlier phase of breast cancer treatment. LA function was also affected, mirroring LV volumetric and functional changes. Diastolic dysfunction, assessed through LA reservoir strain, was impaired in association with CTRCD. 3D-TTE usefulness in the surveillance and monitoring of CTRCD goes beyond systolic LV function assessment, allowing a detailed LA function analysis. Funding Acknowledgement Type of funding sources: None.

Intraoperative echocardiography for electrode implantation into the left bundle branch region in patients with indications for cardiac resynchronization therapy

Abstract Background Left bundle branch (LBB) pacing recently became a novel pacing modality for cardiac resynchronization therapy (CRT). Purpose We evaluated the feasibility and utility of intraoperative Echocardiography (TTE) for implantation Select Secure pacing lead 3830 through interventricular septum (IVS) into the LBB area. Methods 60 patients with LBB block and indications for CRT in the period 2019–2020 underwent electrode implantation into the LBB area. Immediately before implantation, the IVS thickness and density (color scale ZOOM function, Siemens SC 2000 Prime) in the basal and middle region of IVS was assessed. White color corresponds to areas with a large amount of fibrosis, gray – conditionally viable myocardium. The implantation of the electrode by screwing it clockwise was carried out under constant echocardiographic control of the electrode advance from the right ventricle perpendicular to the IVS to the left ventricular (LV) endocardium. The ultimate target was the LV subendocardial region. After reaching the end position, the duration of mechanical LV systole was assessed (Velocity Vector 2D Speckle Analysis). Opposite wall delay (OWD) &amp;lt;120 ms – considered as a marker of good mechanical resynchronization. Results Technically, the procedure was successful in 54 from 60 patients (90%). The average IVS thickness at the site of successful implantation was 11±3, the maximum thickness was 18 mm. Average number of attempts to screw in the electrode in IVS per patient – 4.2±2.1. Predictors of failure were: 2 – IVS thickness over 15 mm throughout entire length and in 4 cases – total IVS fibrosis, despite the normal thickness (9±3). In two cases IVS perforation was detected, corrected by immediate electrode repositioning. In 4 (6.6%) cases, the initial point of implantation was not effective: OWD &amp;gt;120 ms, which required reimplantation of the lead in a more optimal position. Conclusion The use of intraoperative echocardiography during electrode implantation in the IVS allows choosing an optimal site for successful implantation, reliably monitoring the electrode position during implantation, and assessing LV intraventricular asynchronism and effectiveness of resynchronization Funding Acknowledgement Type of funding sources: None.

Assessments of left ventricular systolic and diastolic functions with tissue Doppler imaging and myocardial performance index in children with chronic kidney disease.

This study aimed to document early left ventricular (LV) dysfunction in chronic kidney disease (CKD) using methods such as tissue Doppler imaging and the myocardial performance index (MPI). A total of 40 patients diagnosed with CKD (mean age, 10.1 ± 4.1 years) and 40 sex- and age-matched healthy controls (mean age, 9.6 ± 4.3 years) were examined. In the patient group, 20 patients had early stage (Stage 2-3) CKD and 20 patients had late-stage (stage 4-5) CKD, and 18 patients had hypertension. The pulmonary artery systolic pressure (PAPs) and LV mass index (LVMI) were significantly higher in the patient group (P < 0.05). The LV septal and lateral margins of the mitral annulus E'/A' ratio, E/E' ratio and MPI results were significantly different between the groups (P < 0.05). The MPI scores were higher in late-stage CKD than in early stage CKD (P < 0.05). The E'/A' ratio was lower and the MPI was higher in the hypertensive CKD group compared with the normotensive CKD group (P < 0.05). The E/E' ratio was correlated positively with the LVMI, and the PAPs, and negatively with glomerular filtration rate, S' value, E'/A' ratio. The MPI was correlated positively with blood pressure, LVMI, PAPs, and the S value, and negatively with the E'/A' ratio. The E'/A' ratio, the E/E' ratio, and the isovolumetric relaxation time measured by tissue Doppler imaging is highly accurate and easily applicable for detecting diastolic LV function, and the MPI is suitable for detecting both systolic and diastolic LV dysfunction. Their routine use may be useful in evaluating LV functions in children with CKD.

Belgian Heart Rhythm Meeting 2021: Book of Abstracts

Background In patients with atrial fibrillation (AF) and heart failure (HF), pulmonary vein isolation (PVI) was shown to be superior to pharmacological therapy. However, only a variable percentage of patients improves and how these patients should be identified remains uncertain. Objective to investigate the predictors of left ventricular (LV) systolic function recovery after PVI and to develop a prediction model for individualised assessment. Methods We conducted an observational, retrospective, single centre study of consecutive patients with AF and HF undergoing PVI. Patients were divided into Responder vs. Non-Responder (NR) according to the ‘Universal definition and classification of HF’. Clinical predictors were evaluated by multivariate logistic regression analysis and cross-validation technique. Independent predictors were used to build an internally validated prediction model. Results One-hundred-and-eleven patients (61 ± 10 years, 61% male) were included and followed for 34 (20–58) months. Patients in the Responder group had significantly shorter QRS duration (97 vs. 137 ms, p < 0.001) and less dilated left atria (38 vs. 50 mL/m2, p < 0.001). Persistent AF and concomitant AF-HF diagnoses were more frequent among Responders. AF/AFL/AT recurrence was 35% in the Responder vs. 49% in the Non-Responder group (p = 0.2). Time to recovery in the Responder-Group was 4.8 (0.6–10.4) months. The absence of known underlying Cardiomyopathy (CMP), persistent AF, left atrial volume index (LAVI) < 50ml/m2, and QRS <120msec were significant predictors of systolic function recovery and were included in the Antwerp Score. Patients with Antwerp Score ≤1 had a 90% likelihood of Response compared to 5% in patients with ≥3 points. Conclusions HF Patients with systolic LV function recovery after PVI have less frequently wide QRS complex and known underlying CMP, less dilated left atria, and more frequently persistent AF. A new score system based on four clinical parameters (QRS duration, LA volume, persistent AF and known underlying CMP) can accurately predict LV function recovery after PVI.

Echocardiographic Evaluation of LV Function in Patients with Tachyarrhythmia and Reduced Left Ventricular Function in Response to Rhythm Restoration.

Aims: Tachyarrhythmia due to atrial fibrillation (AF) is often associated with reduced left ventricular (LV) function and has been proposed to cause arrhythmia-induced cardiomyopathy (AIC). However, the precise diagnostics of AIC and reversibility after rhythm restoration are poorly understood. Our aim was to investigate systolic LV function in tachycardic AF and to evaluate the direct effect of rhythm restoration. Methods: We prospectively studied 24 patients (71% male, age 65 ± 9 years) with tachycardic AF and newly diagnosed reduced left ventricular ejection fraction (LVEF). Just before and immediately after electrical cardioversion (ECV), transthoracic echocardiography was performed. Geometric as well as functional data were assessed. Results: Patients presented with a heart rate (HR) of 117.4 ± 21.6/min and a 2D-/3D-LVEF of 32 ± 9/31 ± 8%. ECV to sinus rhythm normalized HR to 77 ± 11/min with an increase of 2D-/3D-LVEF to 37 ± 9/37 ± 10% (p < 0.01 vs. baseline, each). Left ventricular geometry changed with an increase of end-diastolic volume (LVEDV) while end-systolic volume (LVESV) remained unchanged. Parameters concerning myocardial deformation (global longitudinal strain (GLS), strain rate (SR)) decreased whereas the RR interval-corrected GLS (GLSc) remained unchanged. In a simple linear regression model, GLS correlated with 2D- and 3D-LVEF not only before (pre) ECV, but also after (post) ECV. We demonstrate that the increase of LVEF and GLS (ratios pre/post) correlates with the change of HR (ΔHR; R2 = 0.20, 0.33 and 0.32, p < 0.05 each), whereas ratios of GLSc and SR do not significantly correlate with HR (R2 = 0.03 and 0.01, p = n.s. each). Conclusion: In patients with tachyarrhythmia and reduced ejection fraction, ECV leads to immediate improvement in EF and GLS while HR-corrected LV contractility remains unchanged. This suggests that the immediate effects of rhythm restoration are mostly related to changes in left ventricular volume, but not to an acute improvement of heart-rate independent contractility.

COVID-19 and Heart Failure: From Epidemiology During the Pandemic to Myocardial Injury, Myocarditis, and Heart Failure Sequelae.

A close and intriguing relationship has been suggested between heart failure (HF) and coronavirus disease 2019 (COVID-19). First, COVID-19 pandemic represented a global public health emergency in the last year and had a catastrophic impact on health systems worldwide. Several studies showed a reduction in HF hospitalizations, ranging from 30 to 66% in different countries and leading to a subsequent increase in HF mortality. Second, pre-existing HF is a risk factor for a more severe clinical course of COVID-19 and an independent predictor of in-hospital mortality. Third, patients hospitalized for COVID-19 may develop both an acute decompensation of chronic HF and de-novo HF as a consequence of myocardial injury and cardiovascular (CV) complications. Myocardial injury occurred in at least 10% of unselected COVID-19 cases and up to 41% in critically ill patients or in those with concomitant CV comorbidities. Few cases of COVID-19-related acute myocarditis, presenting with severe reduction in the left ventricular (LV) ejection fraction and peculiar histopathological findings, were described. However, recent data suggested that COVID-19 may be associated with both systolic and diastolic LV dysfunction, with LV diastolic impairment, pulmonary hypertension, and right ventricular dysfunction representing the most frequent findings in echocardiographic studies. An overview of available data and the potential mechanisms behind myocardial injury, possibly leading to HF, will be presented in this review. Beyond the acute phase, HF as a possible long-term consequence of cardiac involvement in COVID-19 patients has been supposed and need to be investigated yet.

Usefulness of Left Ventricular Myocardial Deformation in Children Hospitalized for Acute Myocarditis who Develop Arrhythmias

Cardiac arrhythmias occur in 3-40% of patients with acute myocarditis and cause significant morbidity and mortality. Myocardial injury also results in abnormal myocardial deformation. The relationship between left ventricular (LV) deformation, measured by two-dimensional speckle tracking echocardiography (2D-STE), and arrhythmia in pediatric myocarditis is unknown. We evaluated the association between 2D-STE and arrhythmias in children hospitalized with acute myocarditis. We reviewed patients ≤ 18 years hospitalized for acute myocarditis from 2008 to 2018. Arrhythmias were defined as 1) non-sustained or sustained ventricular tachycardia or ventricular fibrillation, 2) sustained supraventricular tachycardia (SVT), 3) high-grade or complete heart block, and 4) any arrhythmia treated with an antiarrhythmic medication. Systolic LV strain values (including LV global longitudinal strain (GLS), global circumferential strain (GCS), and six segments of LV regional long axis strain) were obtained from initial echocardiograms during hospitalization. Of 66 patients hospitalized, 23 (35%) had arrhythmias. SVT was the predominant arrhythmia (74%). Global and regional strain indices were reduced in the arrhythmia group: LV GLS [-8.9 (IQR -13.6, -6.1) vs. -13.7 (IQR -16.9, -9.7), p=0.038]; basal inferior/septal [-10.7 (IQR -15.5, -7.8) vs. -16.4 (IQR -18, -11.8), p=0.009]; basal anterior/lateral [-7.1 (IQR -12.8, -4.7) vs. -9.4 (IQR -16.7, -7.4), p=0.025]; and mid inferior/septal segments [-9 (IQR -13, -7.7) vs. -14.1 (IQR -22.5, -10.7), p=0.007]. After controlling for age, reductions in GLS and segmental strain in the two basal and two mid-segments were associated with increased arrhythmia occurrence (p <0.05). Our findings suggest that echocardiographic LV deformation by 2D-STE may be useful in identifying pediatric patients with acute myocarditis at risk for arrhythmias.

Efficacy and safety of left bundle branch area pacing versus right ventricular apex pacing in patients with atrioventricular block: study protocol for a randomised controlled trial

IntroductionLeft bundle branch area pacing (LBBaP) is a relatively new approach for physiologic pacing. A limited number of retrospective clinical studies, featuring small sample sizes, have shown that compared with...