Systolic Impairment Research Articles

Subclinical cardiac impairments in fetuses conceived through assisted reproductive technology by speckle tracking echocardiography.

To evaluate the changes of cardiac morphology and function in fetuses conceived through assisted reproductive technologies (ART) by speckle tracking echocardiography. A retrospective study was conducted in 101 spontaneously conceived (SC) fetuses and 99 ART-conceived ones. Fetal echocardiography was performed, fetal cardiac morphology and function were analyzed using two-dimensional speckle tracking software, including global sphericity index (GSI), global longitudinal strain (GLS), fractional area change (FAC) of the left and right ventricles, as well as segmental sphericity index (SI), end-diastolic diameter (ED), and fractional shortening (FS) in 24 segments. Compared to the SC fetuses, the ART-conceived fetuses exhibited decreased GSI (median [interquartile range], 1.22 [1.16-1.27] vs. 1.18 [1.11-1.24], p=0.007), decreased right ventricular GLS (24.9 [21.5-27.6] vs. 23.2 [20.4-26.8], p=0.026), and decreased right ventricular FAC (mean±standard deviation, 39.7±6.4 vs. 37.2±7.1, p=0.003). Analysis of the 24 segments showed that ART-conceived fetuses had reduced SI in the apical segments of right ventricle and increased ED in several segments of the right ventricle. Fetuses conceived through ART had a more spherical shape of the global heart and predominantly right-sided cardiac remodeling and systolic function impairment.

Troponin I Tyrosine Phosphorylation Beneficially Accelerates Diastolic Function.

A healthy heart is able to modify its function and increase relaxation through post-translational modifications of myofilament proteins. While there are known examples of serine/threonine kinases directly phosphorylating myofilament proteins to modify heart function, the roles of tyrosine (Y) phosphorylation to directly modify heart function have not been demonstrated. The myofilament protein TnI (troponin I) is the inhibitory subunit of the troponin complex and is a key regulator of cardiac contraction and relaxation. We previously demonstrated that TnI-Y26 phosphorylation decreases calcium-sensitive force development and accelerates calcium dissociation, suggesting a novel role for tyrosine kinase-mediated TnI-Y26 phosphorylation to regulate cardiac relaxation. Therefore, we hypothesize that increasing TnI-Y26 phosphorylation will increase cardiac relaxation in vivo and be beneficial during pathological diastolic dysfunction. The signaling pathway involved in TnI-Y26 phosphorylation was predicted in silico and validated by tyrosine kinase activation and inhibition in primary adult murine cardiomyocytes. To investigate how TnI-Y26 phosphorylation affects cardiac muscle, structure, and function in vivo, we developed a novel TnI-Y26 phosphorylation-mimetic mouse that was subjected to echocardiography, pressure-volume loop hemodynamics, and myofibril mechanical studies. TnI-Y26 phosphorylation-mimetic mice were further subjected to the nephrectomy/DOCA (deoxycorticosterone acetate) model of diastolic dysfunction to investigate the effects of increased TnI-Y26 phosphorylation in disease. Src tyrosine kinase is sufficient to phosphorylate TnI-Y26 in cardiomyocytes. TnI-Y26 phosphorylation accelerates in vivo relaxation without detrimental structural or systolic impairment. In a mouse model of diastolic dysfunction, TnI-Y26 phosphorylation is beneficial and protects against the development of disease. We have demonstrated that tyrosine kinase phosphorylation of TnI is a novel mechanism to directly and beneficially accelerate myocardial relaxation in vivo.

Heart rhythm complexity analysis in patients with inferior ST-elevation myocardial infarction

Heart rhythm complexity (HRC), a subtype of heart rate variability (HRV), is an important tool to investigate cardiovascular disease. In this study, we aimed to analyze serial changes in HRV and HRC metrics in patients with inferior ST-elevation myocardial infarction (STEMI) within 1 year postinfarct and explore the association between HRC and postinfarct left ventricular (LV) systolic impairment. We prospectively enrolled 33 inferior STEMI patients and 74 control subjects and analyzed traditional linear HRV and HRC metrics in both groups, including detrended fluctuation analysis (DFA) and multiscale entropy (MSE). We also analyzed follow-up postinfarct echocardiography for 1 year. The STEMI group had significantly lower standard deviation of RR interval (SDNN), and DFAα2 within 7 days postinfarct (acute stage) comparing to control subjects. LF power was consistently higher in STEMI group during follow up. The MSE scale 5 was higher at acute stage comparing to control subjects and had a trend of decrease during 1-year postinfarct. The MSE area under scale 1–5 showed persistently lower than control subjects and progressively decreased during 1-year postinfarct. To predict long-term postinfarct LV systolic impairment, the slope between MSE scale 1 to 5 (slope 1–5) had the best predictive value. MSE slope 1–5 also increased the predictive ability of the linear HRV metrics in both the net reclassification index and integrated discrimination index models. In conclusion, HRC and LV contractility decreased 1 year postinfarct in inferior STEMI patients, and MSE slope 1–5 was a good predictor of postinfarct LV systolic impairment.

A multimodality assessment of the protective capacity of statin therapy in a mouse model of radiation cardiotoxicity

PurposeDespite technological advances in radiotherapy (RT), cardiotoxicity remains a common complication in patients with lung, oesophageal and breast cancers. Statin therapy has been shown to have pleiotropic properties beyond its lipid-lowering effects. Previous murine models have shown statin therapy can reduce short-term functional effects of whole-heart irradiation. In this study, we assessed the efficacy of atorvastatin in protecting against the late effects of radiation exposure on systolic function, cardiac conduction, and atrial natriuretic peptide (ANP) following a clinically relevant partial-heart radiation exposure. Materials and MethodsFemale, 12-week old, C57BL/6j mice received an image-guided 16 Gy X-ray field to the base of the heart using a small animal radiotherapy research platform (SARRP), with or without atorvastatin from 1 week prior to irradiation until the end of the experiment. The animals were followed for 50 weeks with longitudinal transthoracic echocardiography (TTE) and electrocardiography (ECG) every 10 weeks, and plasma ANP every 20 weeks. ResultsAt 30–50 weeks, mild left ventricular systolic function impairment observed in the RT control group was less apparent in animals receiving atorvastatin. ECG analysis demonstrated prolongation of components of cardiac conduction related to the heart base at 10 and 30 weeks in the RT control group but not in animals treated with atorvastatin. In contrast to systolic function, conduction disturbances resolved at later time-points with radiation alone. ANP reductions were lower in irradiated animals receiving atorvastatin at 30 and 50 weeks. ConclusionsAtorvastatin prevents left ventricular systolic dysfunction, and the perturbation of cardiac conduction following partial heart irradiation. If confirmed in clinical studies, these data would support the use of statin therapy for cardioprotection during thoracic radiotherapy.

Shared and distinguishing phenotypic characteristics of filamin c and desmoplakin cardiomyopathy

Abstract Background Rare truncating variants in the genes Filamin C (FLNC) and Desmoplakin (DSP) are increasingly recognised causes of Dilated Cardiomyopathy and Arrhythmogenic Cardiomyopathy (1,2). A direct comparison of both genotypes is needed to aid in subclassification and genotype-specific risk modelling. Purpose We sought to identify shared and distinguishing clinical characteristics and imaging phenotypes between FLNC and DSP cardiomyopathy. Methods 41 patients with ‘pathogenic’ or ‘likely pathogenic’ FLNC or DSP variants by American College of Medical Genetics (ACMG) criteria were identified from a tertiary centre cardiovascular genetics laboratory. Clinical, genetic and imaging data were compiled. Continuous variables are presented as median [IQR] or mean±SD and analysed by nonparametric Mann Whitney U or t-test. Categorical variables were analysed by Chi-Squared or Fisher’s exact test. Results FLNC and DSP cohorts included a similar proportion of patients with truncating variants (91% vs 100%) and female sex (12/21, 57% vs 13/20, 65%). FLNC patients were younger (median age 30 [13-51] vs 57 [41-65] years, p<0.0008) and more likely to present with sustained ventricular arrhythmia (5/21 24% vs 3/20, 15%) (Table 1). Acute myocarditis episodes were exclusively linked to DSP cardiomyopathy (4/20, 20%) with no association to FLNC (0/21, 0%, p<0.05). FLNC cardiomyopathy patients had normal left ventricular (LV) systolic function (LVEF 57±9% SD vs 46±13% DSP, p<0.03) and normal left ventricular cavity side (mean indexed LV end diastolic volume (EDV) 85±12 vs 112±26ml/m2 DSP, p<0.02) (Table 2). Both FLNC and DSP cause exclusive left ventricular or biventricular late gadolinium enhancement (75% Vs 82%) on cardiac magnetic resonance imaging (MRI). Fibrosis was predominantly in a subepicardial distribution in both cohorts (66% FLNC vs 57% DSP). In FLNC, circumferential fibrosis was the most frequent pattern of distribution (5/9, 55%), whereas in DSP inferior and lateral wall fibrosis was the predominant feature (8/14, 57%). There were no cases of isolated RV involvement and no cases fulfilled ‘definite’ ARVC taskforce diagnostic criteria. Over a follow up of median 45months, there was no significant difference in the proportion of FLNC and DSP patients experiencing a composite end point of LVAD implantation, heart transplant, aborted sudden cardiac death or mortality (7/21, 33% FLNC Vs 7/20, 29% DSP p>0.99). Conclusion Normal systolic function with marked circumferential fibrosis is the predominant feature of FLNC cardiomyopathy whereas mild LV dilatation, mild systolic impairment and inferolateral fibrosis are more frequent in DSP cardiomyopathy. Myocarditis episodes are a distinguishing feature of DSP cardiomyopathy, suggesting a different underlying molecular mechanism driven by inflammation. The overall clinical trajectory of FLNC and DSP cardiomyopathy patients are comparable.

Abstract 13706: Determinants of Right Ventricular Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction: The PARAGON-HF Trial Experience

Introduction: Right ventricular dysfunction (RVD) is a major prognostic factor in patients with heart failure with preserved ejection fraction (HFpEF), however determinants of RVD in HFpEF are not well described. Although sex-specific mechanisms have been incriminated in the development of HFpEF, it is unclear whether this is also true for RVD. Goals: (1) Assess the prevalence of RVD (defined as a tricuspid annular plane systolic excursion [TAPSE] <1.7 cm, a fractional area change [FAC] <35% or a RV free wall longitudinal strain [RVFWLS] <20%, absolute value) in patients with HFpEF; (2) identify determinants of RVD, overall and according to sex, in patients with HFpEF. Methods: We used data from patients enrolled in the echocardiographic sub-study of the PARAGON-HF trial with adequate image quality (N=809, 53% women, mean age 74±8 years). Determinants of RVD, in the whole study population and according to sex, were identified using a multivariable logistic regression model. Results: There were 461 patients (57%) with RVD. After multivariable adjustment, RVD was cross-sectionally associated with a history of atrial fibrillation of flutter (AFF), older age, higher heart rate, greater LV mean wall thickness and higher NT-proBNP values. Systolic blood pressure and LV global longitudinal strain (absolute value) showed an inverse association ( Figure ). These results were consistent between men and women, except for AFF and LV mean wall thickness, which were associated with a greater likelihood of RVD in men (OR 2.46, 95%CI 1.33-4.56, OR 1.61, 95%CI 1.18-2.21 respectively) but not in women (OR 0.99, 95%CI 0.58-1.68, OR 0.90 95%CI 0.69-1.17 respectively, p-values for interaction=0.028 and 0.006). Conclusions: RVD was highly prevalent in our study population. Determinants of RVD included AFF, LV remodeling and systolic impairment, and increased NT-proBNP levels. Differences between men and women suggest gender-specific mechanisms in the development of RVD in HFpEF.

Speckle tracking tissue motion mitral annulus displacement to assess early changes in the left ventricle and its association with lung function in patients with chronic obstructive pulmonary disease.

To evaluate the early changes in left ventricular (LV) in patients with chronic obstructive pulmonary disease (COPD) by measuring tissue motion mitral annulus displacement (TMAD) and three-dimensional (3D) parameters using speckle tracking imaging (STI), and to explore its correlation with lung function. Forty two COPD patients (GOLD I, GOLD II, GOLD III) and 30 healthy individuals (control group) were included. STI was used to assess the changes in LV structure and systolic function. Receiver operating characteristic (ROC) curves were drawn, and correlations among TMAD parameters, LV systolic function, structural, pulmonary artery systolic pressure (PASP), and lung function were analyzed. Compared to the control group, COPD patients were able to undergo LV remodeling, with a decrease in the absolute value of global longitudinal strain (GLS) and TMAD, but no significant modification of LVEF. Correlation analysis showed that TMAD was positively related to the absolute value of GLS (r > 0.51, P < 0.01) and predicted forced expiratory volume in the first second (FEV1%) (r > 0.56, P < 0.01), and negatively to PASP (r < -0.52, P < 0.01). The LV posterior wall thickness (LVPWd), relative wall thickness (RWT), end-diastolic volume (LVEDV) and PASP negatively correlated with FEV1%. The LV geometric changes and systolic function impairment in COPD patients were found to correlate with airflow restriction (FEV1%). TMAD aided in detection of early changes in LV systolic function in COPD patients. It negatively correlated with PASP and positively with FEV1%. Moreover, it was more convenient than GLS.

Right Ventricular Function in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia: From the CTOXALL Study

There are limited data regarding right ventricle (RV) impairment in long-term survivors of childhood acute lymphoblastic leukemia (CLS). The aim of this study was to assess RV function in these patients using echocardiographic conventional measurements and automated RV strain. Echocardiographic recordings of 90 CLS and 58 healthy siblings from the CTOXALL cohort were analyzed. For group comparisons, inverse probability weighting was used to reduce confounding. The CLS group (24.6 ± 9.7 years, 37.8% women) underwent an echocardiographic evaluation 18 (11–26) years after the diagnosis. RV systolic dysfunction was found in 16.7% of CLS individuals using RV free-wall strain (RVFWS) compared to 2.2 to 4.4% with conventional measurements. RV systolic function measurements were lower in the CLS than in the control group: TAPSE (23.3 ± 4.0 vs. 25.2 ± 3.4, p = 0.004) and RVFWS (24.9 ± 4.6 vs. 26.8 ± 4.7, p = 0.032). Modifiable cardiovascular risk factors such as obesity (p = 0.022) and smoking (p = 0.028) were independently associated with reduced RVFWS. In conclusion, RV systolic function impairment was frequent in long-term survivors of childhood leukemia, underscoring the importance of RV assessment, including RVFWS, in the cardiac surveillance of these patients.

Sustained Increases in Cardiomyocyte Protein O-Linked β-N-Acetylglucosamine Levels Lead to Cardiac Hypertrophy and Reduced Mitochondrial Function Without Systolic Contractile Impairment.

Background Lifestyle and metabolic diseases influence the severity and pathogenesis of cardiovascular disease through numerous mechanisms, including regulation via posttranslational modifications. A specific posttranslational modification, the addition of O-linked β-N acetylglucosamine (O-GlcNAcylation), has been implicated in molecular mechanisms of both physiological and pathologic adaptations. The current study aimed to test the hypothesis that in cardiomyocytes, sustained protein O-GlcNAcylation contributes to cardiac adaptations, and its progression to pathophysiology. Methods and Results Using a naturally occurring dominant-negative O-GlcNAcase (dnOGA) inducible cardiomyocyte-specific overexpression transgenic mouse model, we induced dnOGA in 8- to 10-week-old mouse hearts. We examined the effects of 2-week and 24-week dnOGA overexpression, which progressed to a 1.8-fold increase in protein O-GlcNAcylation. Two-week increases in protein O-GlcNAc levels did not alter heart weight or function; however, 24-week increases in protein O-GlcNAcylation led to cardiac hypertrophy, mitochondrial dysfunction, fibrosis, and diastolic dysfunction. Interestingly, systolic function was maintained in 24-week dnOGA overexpression, despite several changes in gene expression associated with cardiovascular disease. Specifically, mRNA-sequencing analysis revealed several gene signatures, including reduction of mitochondrial oxidative phosphorylation, fatty acid, and glucose metabolism pathways, and antioxidant response pathways after 24-week dnOGA overexpression. Conclusions This study indicates that moderate increases in cardiomyocyte protein O-GlcNAcylation leads to a differential response with an initial reduction of metabolic pathways (2-week), which leads to cardiac remodeling (24-week). Moreover, the mouse model showed evidence of diastolic dysfunction consistent with a heart failure with preserved ejection fraction. These findings provide insight into the adaptive versus maladaptive responses to increased O-GlcNAcylation in heart.

A rare cause of mixed hypertrophic and dilated phenotype cardiomyopathy – the MELAS syndrome

Abstract Introduction MELAS is a systemic hereditary condition that can present as hypertrophic or mixed hypertrophic and dilated phenotype cardiomyopathy in young individuals, although a late-onset form is also described in the literature. Genetic testing is essential for correct diagnosis and appropriate management. Case presentation We present the case of a 22-year-old male who was referred to our center after being diagnosed with NYHA class III heart failure with a mixed hypertrophic and dilated cardiomyopathy. His medical history included stroke episodes, seizures, progressive hypoacusis, neurocognitive impairment, and muscle atrophy. Lactic acidosis and elevated CK levels were also noted. The ECG revealed short PR interval and delta wave in lateral leads. TTE showed mildly dilated and hypertrophied LV and RV with severe biventricular systolic impairment. The CMR study was relevant for ring-like subepicardial fibrosis, predominantly in the medium and apical segments. Brain MRI showed multifocal supratentorial subcortical stroke-like lesions in both cerebral hemispheres, involving multiple vascular territories and following a migratory pattern. Genetic testing confirmed a pathogenic MT-TL1 mutation (m.324A&gt;G) and the patient was diagnosed with MELAS. Further management included specific lifestyle recommendations and cascade genetic screening, as well as starting GDMT for HFrEF. Three months after discharge, his clinical status improved. However, the LVEF remained reduced. After careful consideration, an ICD was implanted for primary prevention. Conclusion A red-flag approach in this young patient, which took into consideration the stroke-like episodes, lactic acidosis, seizures, hypoacusis, myopathy, as well as the short PR interval, led to the correct diagnosis, further confirmed by using the appropriate genetic test. Failure to diagnose affects the patient’s prognosis, as their prognosis and clinical status are influenced by enforcing specific recommendations.

Association between systemic inflammatory response index and left ventricular remodeling and systolic dysfunction in atrial fibrillation patients

BackgroundCardiac remodeling and dysfunction can be caused by atrial fibrillation (AF). The aim of this research is to investigate the relationship between the systemic inflammatory response index (SIRI) and left ventricular (LV) remodeling and systolic function in individuals with AF.Methods416 patients with AF who were admitted to the Second Department of Cardiology in the East Ward of the Qingdao Municipal Hospital between January 2020 and May 2022 were included in the present retrospective research. The relationship between SIRI and various cardiac parameters was analyzed. The patients’ left atrial (LA) enlargement and left ventricular (LV) hypertrophy and systolic dysfunction were evaluated. SIRI was calculated by the formula: neutrophil × monocyte/lymphocyte.ResultsSIRI significantly correlated with LV end-diastolic diameter (LVDd), LV posterior wall thickness at end-diastole (LVPWTd), interventricular septal thickness at end-diastole (IVSTd), LV mass index (LVMI), LV ejection fraction (LVEF), LA diameter (LAD), C-reactive protein (CRP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with AF. In multivariate linear regression analyses, SIRI was discovered to be significantly related to LVMI (ln-transformed) (p = 0.025), LVEF (ln-transformed) (p = 0.005), and LAD (ln-transformed) (p = 0.007). In multivariate logistic regression, the highest quartile of SIRI (SIRI > 1.62) was significantly associated with LV hypertrophy (p = 0.026), impaired LV systolic function (p = 0.002), and LA enlargement (p = 0.025).ConclusionsSIRI was significantly associated with LV remodeling and systolic function impairment in patients with AF. SIRI may serve as a reliable and convenient inflammatory biomarker for detecting impaired cardiac structure and systolic function in patients with AF.

Right ventricular strain by speckle tracking echocardiography in patients with systemic scleroderma and absence of pulmonary hypertension

Abstract Funding Acknowledgements Type of funding sources: None. Introduction In patients with scleroderma the morphological remodeling and alteration of right ventricular (RV) function begins even before the setting of pulmonary artery hypertension (PAH). These alterations are associated with worse outcomes and high mortality rate as 30% of deaths are attributed to cardiovascular causes followed by respiratory causes (17%). Purpose Early detection of RV dysfunction is possible using advanced imaging techniques and can lead to specific therapeutic management before installation of PAH and clinical signs and symptoms of heart failure . Purpose of this study is to evaluate new indices, based on speckle tracking echocardiography, for identification of subclinical RV systolic failure. Methods Thirty (30) scleroderma patients without any signs or symptoms of PAH and forty (40) healthy subjects were included in the present study. Two-dimensional echocardiography (2DE) and two-dimensional speckle-tracking echocardiography (2DSTE) were performed. All the usual 2DE, Doppler and tissue Doppler imaging measurements were obtained for the evaluation of RV function. Moreover, TAPSE, maximum systolic myocardial velocity from TDI of lateral tricuspid valve annulus (SRV), auto RV global longitudinal strain (aRVGLS) and auto RV free wall longitudinal strain (aRVFWLS) by 2DSTE were measured. aRVGLS and aRVFWLS are new indices, with appropriate RV function echo logistics in new technology echo systems, independent from known manual measurements. Results In scleroderma patients significantly higher systolic pulmonary artery pressure was recorded, although it remained within normal limits in both groups (24.6+-5.4mmHg vs 19.2+-5.9 mmHg) . Scleroderma patients had significant decreased RV systolic function with significantly lower TAPSE and SRV. Both aRVGLS and aRVFWLS were also lower in scleroderma patients compared to the control group (−18.6+-2.7 vs −23.1+-2.3 % and −25.4+-3.1 vs −26.4+-2.2 % respectively). aRVGLS was the best significant predictor of early RV systolic impairment in patients with scleroderma.The difference in aRVFWLS was not significant. Conclusions Scleroderma is a severe systematic disease associated with high mortality rates. RV remodeling, dysfunction, and progressive pulmonary artery hypertension are among the most important internal organ manifestations of this disease. Early detection of RV dysfunction before installation of pulmonary hypertension is possible by 2DSTE, and may be helpful to guide further therapy in these patients.

New insights into left ventricular mechanics assessed by cardiac magnetic resonance and myocardial work analysis in non-compaction

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): 2 National Grants of the Romanian Ministry of Research and Innovation - UEFISCDI: "Heart Preserved" and "PRO HEART 3D. Background The so-called left ventricle non-compaction (LVNC), better described as excessive trabeculation, is a highly debated myocardial phenotype. One of the main debates is whether excessive trabeculation is a remodeling feature due to volume load and LV dilation, or is the primary cause of LV dysfunction with LV dilation in the advanced stages. Purpose We aim to evaluate the relationship of LV trabeculations with LV volumes and systolic function in patients with LVNC. Methods 50 patients with suspected LVNC were evaluated by cardiac magnetic resonance (CMR), transthoracic echocardiography (TTE), and N-terminal prohormone of brain natriuretic peptide (NTproBNP). To avoid over-diagnosis of LVNC, we analyzed 27 patients confirmed by CMR, with a positive Jacquier criterion [the percentage of non-compact myocardium mass (NCCM) &amp;gt;20%], excluding those having only a positive Petersen criterion. By CMR, we measured left ventricular end-diastolic volume index (LVEDVi), left ventricular end-systolic volume index (LVESVi), and left ventricular ejection fraction (LVEF). By TTE, we measured global longitudinal strain (GLS), and we performed myocardial work analysis (MWA), as a less afterload-dependent parameter than GLS, measuring global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). Results Clinical and biological characteristics, CMR, GLS, and MWA results are detailed in Table 1. Mean percentage of NCMM was 29.45±10.3%. 89% of patients had HF, with LVEF ranging from 17% to 73%. There was no correlation between percentage of NCMM and LVEDVi. Instead, percentage of NCMM correlated positively with LVESVi (R=0.389, p = 0.045) and negatively with LVEF (R=-0.507, p = 0.007) (Figure 1). There was also no correlation between percentage of NCMM and GLS. Percentage of NCMM correlated negatively with GWE (R=-0.539, p = 0.004) (Figure 1), but not with GWI (p = 0.161), GCW (p = 0.249), or GWW (p = 0.060). By linear regression, per 10% increase in NCMM, LVEF decrease by 8.3% and GWE decrease by 4.2%. Percentage of NCCM had a trend to correlate positively with logNTproBNP (R=0.321, p = 0.103). Conclusions Our results suggest that excessive trabeculation in patients with LVNC is not a marker of chronic preload. LVNC seems to be a distinct cardiomyopathy, with a spectrum of systolic impairment proportional to the degree of hypertrabeculation. MWA is a promising tool to evaluate the functional implication of LV trabeculations.

Association of left ventricular ejection fraction and long axis function across health and disease

Abstract Funding Acknowledgements Type of funding sources: None. Background Global longitudinal shortening (GLSh) 1,2 and left ventricular ejection fraction (LVEF) are different measures of left ventricular function. LVEF is well-established, but can miss early or mild disease. GLSh, which quantifies long-axis shortening, is easy to measure, and has been shown to have superior reproducibility and prognostication ability than global longitudinal strain3,4. Purpose To assess the relationship between GLSh and EF measured using CMR in a large cohort representing health (healthy volunteers, athletes) and disease (hypertension, aortic stenosis, hypertrophic cardiomyopathy(HCM),cardiac amyloidosis, Fabry disease). Methods CMR scans from a study cohort of 932 subjects were analysed (121 healthy volunteers, 278 athletes, 40 patients with hypertension, 76 severe aortic stenosis, 164 HCM, 51 cardiac amyloidosis, 202 Fabry). EF and GLSh were automatically measured from standard CMR SSFP cine images using machine learning methods described previously3,5. Correlation coefficients between GLSh and LVEF were calculated for each disease category. Normal reference ranges for LVEF and GLSh were estimated from a subset of n=4,342 healthy subjects from the UK Biobank, who had no history of cardiovascular disease or medication use. Results The lower limit of normal in the UK Biobank healthy subjects was 55% for EF and 13% for GLSh. Across the study cohort, for subjects with normal LVEF, only a small minority of healthy volunteers (n=1, 0.8%) and athletes(n=2; 0.7%) had low GLSh, whereas rates increased progressively in hypertension(n=3;9%), Fabry(n=61;31%), aortic stenosis(n=26;44%), HCM (n=87; 56%), and cardiac amyloidosis(N=28; 93%). Conversely, few subjects (n=8/932;0.1%) have the opposite: normal LGSh but low LVEF(Figure 1). The relationship between LVEF and GLSh is shown in Figure 2. Apart from HCM (r=0.019,p = 0.8), all other diseases show a significant association between GLSh and LVEF, with progressively higher correlation from healthy volunteers (r=0.33 p&amp;lt;0.001) to cardiac amyloidosis (r=0.33; p = 0.0016), athletes (r=0.44; p&amp;lt;0.001), and hypertension (R=0.6; p&amp;lt;0.001), with aortic stenosis showing highest correlation (r=0.68,p&amp;lt;0.001). Fabrys patients showed the reverse trend, with an inverse correlation between GLSh and LVEF (r=-0.34; p&amp;lt;0.001). Conclusions In health, impaired GLSh is rare when LVEF is normal, however across diseases with hypertrophy, GLSh impairment is common, illustrating the potential of GLSh to detecting early or mild systolic impairment. There are unexpectedly different associations between GLS and EF. In some diseases, these appears to measure the same aspects (health/AS/hypertension), but in others they are not well correlated with GLS providing new information. In Fabry, there is an unexpected inverse relationship. Further work is needed to understand this.

Association between the atrial tachyarrhythmia recurrence period and long-term major adverse clinical events following catheter ablation for atrial fibrillation

BackgroundWe previously demonstrated the clinical events in patients who underwent catheter ablation (CA) for atrial fibrillation (AF). Data on the association between the period of atrial tachyarrhythmia (ATA) recurrence after CA and long-term major adverse clinical events (MACE) remain unclear. In this study, we evaluated this issue in patients with systolic impairment (left ventricular ejection fraction < 50%) and heart failure with preserved ejection fraction (HFpEF). MethodsWe retrospectively collected data from 81 patients with systolic impairment and 83 patients with HFpEF who underwent CA for AF at our institution (median follow-up: 4.9 [3.6, 6.6] years). In each group, we compared the cumulative incidence of long-term MACE (since 1 year after CA) between patients with and without ATA recurrence at three follow-up periods (3, 6 months, and 1 year after index CA). We evaluated the period of recurrence, which was the most beneficial predictor of MACE among the periods. ResultsIn the systolic impairment group, the cumulative long-term MACE incidence was significantly higher in patients with ATA recurrence than in those without it within 6 months and 1 year (P = 0.04 and P = 0.01, respectively). Recurrence within 1 year showed the highest feasibility for predicting long-term MACE (area under the curve with 95% confidence interval [CI]:0.73 [0.61–0.84]). However, there was no difference in the incidence of MACE between patients with and without recurrence in a group with HFpEF in each period. ConclusionATA recurrence within 1 year could predict long-term MACE in patients with systolic impairment, but not in patients with HFpEF.

α7 nicotinic receptors play a role in regulation of cardiac hemodynamics.

The α7 nicotinic receptors (NR) have been confirmed in the heart but their role in cardiac functions has been contradictory. To address these contradictory findings, we analyzed cardiac functions in α7 NR knockout mice (α7-/-) in vivo and ex vivo in isolated hearts. A standard limb leads electrocardiogram was used, and the pressure curves were recorded in vivo, in Arteria carotis and in the left ventricle, or ex vivo, in the left ventricle of the spontaneously beating isolated hearts perfused following Langedorff's method. Experiments were performed under basic conditions, hypercholinergic conditions, and adrenergic stress. The relative expression levels of α and β NR subunits, muscarinic receptors, β1 adrenergic receptors, and acetylcholine life cycle markers were determined using RT-qPCR. Our results revealed a prolonged QT interval in α7-/- mice. All in vivo hemodynamic parameters were preserved under all studied conditions. The only difference in ex vivo heart rate between genotypes was the loss of bradycardia in prolonged incubation of isoproterenol-pretreated hearts with high doses of acetylcholine. In contrast, left ventricular systolic pressure was lower under basal conditions and showed a significantly higher increase during adrenergic stimulation. No changes in mRNA expression were observed. In conclusion, α7 NR has no major effect on heart rate, except when stressed hearts are exposed to a prolonged hypercholinergic state, suggesting a role in acetylcholine spillover control. In the absence of extracardiac regulatory mechanisms, left ventricular systolic impairment is revealed.

Are There Distinct Cardiovascular Subclasses in Acute Respiratory Distress Syndrome? Maybe.

Are There Distinct Cardiovascular Subclasses in Acute Respiratory Distress Syndrome? Maybe.

Sleep apnea in patients with exacerbated heart failure and overweight

Sleep disorders are a common concomitant comorbidity in patients with heart failure. The aims of our study are to determine the incidence and phenotypic characteristics of sleep apnea in overweight patients with exacerbated heart failure and to assess the degree of involvement of systolic and diastolic function impairment in the individual group. From 100 screened patients with heart failure in our department from 2015 to 2017, 61 met the inclusion criteria and participated in the study. 82% (n = 50) of the patients had obstructive sleep apnea (OSA), and 18% (n = 11) had central sleep apnea (CSA). The CSA group had a significantly lower left ventricular ejection fraction (LVEF) than the OSA group (EF% 49.6 ± 8.5 vs 41.8 ± 11.4; p = 0.013). A negative correlation was found between LVEF and the number of central apnea events (r = −0.52; p < 0.001). More frequent hospitalizations for heart failure (HF) and higher mortality rate were found in the CSA group. Screening for sleep apnea in patients with exacerbated heart failure and obesity is necessary for the complex treatment of these patients.

Atrial functional mitral regurgitation: prevalence, characteristics and outcomes from the National Echo Database of Australia

AimsAtrial functional mitral regurgitation (AFMR) is characterised by left atrial and consequent mitral annular dilatation causing mitral regurgitation. AFMR is likely to become more common with population ageing, alongside increases...

INTRACARDIAC HEMODYNAMICS, CEREBRAL BLOOD FLOW AND MICROEMBOLIC SIGNAL BURDEN IN STABLE CORONARY ARTERY DISEASE PATIENTS WITH CONCOMITANT COVID-19.

The aim: To estimate the changes in intracardiac hemodynamics, cerebral blood flow (CBF), and microembolic signals` (MES) burden in stable coronary artery disease (SCAD) patients with concomitant COVID-19. Materials and methods: The cross-sectional study analyzed the data from 80 patients, being subdivided as follows: group 1 (G1) - SCAD without COVID-19 (n=30); group 2 (G2) - SCAD with concomitant COVID-19 (n=25); group 3 (G3) - COVID-19 without SCAD (n=25). The control group (CG) included 30 relatively healthy volunteers. CBF and total MES count were assessed by transcranial Doppler ultrasound. Results: Transthoracic echocardiography data from G2 revealed the most pronounced left ventricular (LV) dilation and its contractility decline (the rise of end-systolic volume (ESV) and ejection fraction decrease), as compared to G1 and G3. G1-G3 patients (vs. CG) presented with lower peak systolic velocities in all the studied intracranial arteries (middle and posterior cerebral arteries bilaterally, and basilar artery), along with the higher MES count. Such a drop in CBF was the most pronounced in G2. Both G2 and G3 demonstrated the highest amount of MES, with slightly higher count in G2. We built a linear neural network, discriminating the pattern of both higher LV ESV and MES count, being inherent to G2. Conclusions: G2 patients demonstrated the LV dilation and its systolic function impairment, and presented with CBF drop and MES burden increase, being more advanced in contrast to G1 and G3. LV contractility decrease was associated with the higher MES load in the case of SCAD and COVID-19 constellation.