751 Quantitative changes in intracardiac vortices between patients with different ventricular geometry

Aims Over the past decades growing evidence have demonstrated the promising role of intracardiac fluid-dynamics in evaluating cardiac performance. To investigate quantitative changes in vortices parameters in patients with different ventricular geometry. Methods and results We enrolled 50 consecutive patients with one of the following: LV concentric hypertrophy (CH), eccentric hypertrophy (EH), concentric remodelling, and normal LV geometry (CTRL). They underwent a complete echocardiographic examination with intracardiac fluid-dynamic analysis by Color Vector Flow Mapping (Hyperdoppler). The following parameters were obtained: vortex area (VA); vortex length (VL); and vortex depth (VD). Bland Altman Plot has been used to assess intra and inter-observer variability. Mean VD was higher in CR, CH, and EH compared to CTRL (P = 0.013, P = 0.001, and P = 0.022, respectively). Moreover, CH showed higher VL (P = 0.006) and larger VA (P = 0.012) compared to CTRL. A similar trend was noticed in EH patients, despite did not reach statistical significance (P = 0.21 and P = 0.07 for VA and VL, respectively). No significative differences in vortices parameters have been observed between CH and EH. Conclusions This is the first study providing quantitative echocardiographic parameters of vortex location and morphology in different LV geometries. Quantitative fluid-dynamic assessment was feasible and reliable in the whole population.

Utility of Three Adiposity Indices for Identifying Left Ventricular Hypertrophy and Geometric Remodeling in Chinese Children

BackgroundPrevious studies have shown that waist-to-height ratio (WHtR) performed similarly well when compared to body mass index (BMI) and waist circumference (WC) for identifying cardiovascular risk factors. However, to our knowledge, the performance of these three adiposity indices for identifying left ventricular hypertrophy (LVH) and left ventricular geometric (LVG) remodeling in youth has not been assessed. We aimed to determine the utility of BMI, WC and WHtR for identifying LVH and LVG in Chinese children.MethodsThis study included 1,492 Chinese children aged 6-11 years. Adiposity indices assessed were BMI, WC and WHtR. LVH and high relative wall thickness (RWT) were defined using sex- and age-specific 90th percentile values of left ventricular mass index and RWT, respectively, based on the current population. LVG remodeling included concentric remodeling (CR), eccentric hypertrophy (EH) and concentric hypertrophy (CH), which was defined based on the combination of LVH and high RWT.ResultsThe magnitude of association of central obesity defined by WHtR with LVH [odds ratio (OR) =10.09, 95% confidence interval (CI) =6.66-15.29] was similar with general obesity defined by BMI (OR=10.49, 95% CI=6.97-15.80), and both were higher than central obesity defined by WC (OR=6.87, 95% CI=4.57-10.33). Compared with BMI, WHtR had better or similar predictive utility for identifying LVH, EH, and CH [the area under the curve (AUC): 0.84 vs. 0.79; 0.84 vs. 0.77; 0.87 vs. 0.88, respectively]; WC had worse or similar discriminatory utility with AUCs of 0.73, 0.70, 0.83, respectively.ConclusionWHtR performed similarly or better than BMI or WC for identifying LVH and LVG remodeling among Chinese children. WHtR provides a simple and convenient measure of central obesity that might improve the discrimination of children with cardiac structural damage.

Sex differences in left ventricular remodeling in patients with severe aortic valve stenosis

Background Women with severe aortic valve stenosis (AS) have better long-term outcomes after transcatheter aortic valve implantation (TAVI) but worse survival after surgical aortic valve replacement compared to men. Whether this is related to sex differences in left ventricular (LV) remodeling is unknown. Purpose To examine sex differences in LV remodeling and outcomes in patients with severe AS undergoing TAVI. Methods Patients with severe AS who underwent TAVI between 2007 and 2018 with a pre-procedural multidetector row computed tomography (MDCT) scan were included. LV volumes, mass and function were analyzed with MDCT. Patients were classified into 4 LV remodeling patterns based on LV mass index and LV mass-to-volume ratio: 1) normal geometry, 2) concentric remodeling, 3) concentric hypertrophy and 4) eccentric hypertrophy. The primary endpoint was all-cause mortality after TAVI. Results A total of 289 patients (age 80±6 years, 54% male) were included. Women showed smaller LV volumes and mass compared to men. Concentric hypertrophy (50%) was the most frequent pattern of LV remodeling followed by eccentric hypertrophy (33%), normal geometry (13%) and concentric remodeling (4%). Concentric remodeling was more frequently observed in men compared to women (91% vs. 9% respectively, p=0.011). However, no sex differences were observed in the remaining LV remodeling patterns (Figure 1). During a median follow-up of 3.8 (IQR 2.2–5.1) years after TAVI, 87 patients died. Women demonstrated better outcome after TAVI compared to men (log-rank χ2=4.29, p=0.038). The survival benefit of women over men was mainly present among patients with concentric hypertrophy (log-rank χ2=4.91, p=0.027, Figure 2). Conclusion LV concentric and eccentric hypertrophy are similarly observed in men and women with severe AS. Women demonstrated better outcome after TAVI as compared to men, particularly among those with LV concentric hypertrophy. However, the outcome benefit of females after TAVI seems not to be related to sex-differences in LV remodeling. FUNDunding Acknowledgement Type of funding sources: None. Distribution of sex in LV remodeling All-cause mortality after TAVI

Effects of Trandolapril on Structural, Contractile and Electrophysiological Remodeling in Experimental Volume Overload Heart Failure

Chronic volume overload induces multiple cardiac remodeling processes that finally result in eccentric cardiac hypertrophy and heart failure. We have hypothesized that chronic angiotensin-converting enzyme (ACE) inhibition by trandolapril might affect various remodeling processes differentially, thus allowing their dissociation. Cardiac remodeling due to chronic volume overload and the effects of trandolapril were investigated in rats with an aortocaval fistula (ACF rats). The aortocaval shunt was created using a needle technique and progression of cardiac remodeling to heart failure was followed for 24 weeks. In ACF rats, pronounced eccentric cardiac hypertrophy and contractile and proarrhythmic electrical remodeling were associated with increased mortality. Trandolapril substantially reduced the electrical proarrhythmic remodeling and mortality, whereas the effect on cardiac hypertrophy was less pronounced and significant eccentric hypertrophy was preserved. Effective suppression of electrical proarrhythmic remodeling and mortality but not hypertrophy indicates that the beneficial therapeutic effects of ACE inhibitor trandolapril in volume overload heart failure might be dissociated from pure antihypertrophic effects.

Abstract P325: The Role Of Runx1 In Cardiomyocyte Cell Cycle And Ploidy

Adult mammalian cardiomyocytes (CMs) are thought to be post-mitotic and therefore unable to regenerate the myocardium after injury. In recent years various studies have shown that the adult mammalian CM is capable of a small amount of proliferation, potentially restricted to a subset of CMs. One such study demonstrated that having greater percentages of the rare mononuclear diploid cardiomyocyte (MNDCM) is associated with improved outcomes after myocardial infarction (MI). An accompanying genome-wide association analysis identified genetic loci associated with the frequency of the MNDCM population. One candidate to come out of this screen was Runx1. Concurrently, RUNX1 captured the attention of cardiac regeneration researchers due to its increased presence in disease states, with some suggesting it may be a marker for dedifferentiation (fetal gene induction). One recent study demonstrated improved calcium handling and decreased eccentric hypertrophy following RUNX1 ablation after injury, perhaps corroborating the idea that RUNX1 is involved with CM dedifferentiation. We hypothesize that Runx1 influences dedifferentiation in CMs, impacting ploidy, as well as CM cell cycle activity and post-MI outcomes. We found that CM-specific overexpression (OE) of Runx1 results in a doubling of the MNDCM population, thereby validating its influence on the population. Via multiple contexts including postnatal development and adult injury, knocking out Runx1 decreases DNA synthesis while Runx1 OE increases DNA synthesis. Furthermore, an initial analysis of RNAseq data demonstrates that RUNX1 OE in a neonatal mouse hearts demonstrated differential expression in genes related to cardiac conduction, contraction, heart development, regeneration, and regulation of cell differentiation . After MI in the adult mouse heart, the effects of Runx1 OE resulted in transient benefits which included increased cell cycle activity and preservation of function. These data suggest that Runx1 is not simply a marker of CM dedifferentiation, but also a regulator of the process including cell cycle activation. Ongoing work will tease apart this role in more detail and could establish RUNX1 as a prominent therapeutic target for mitigating effects of cardiac injury.

The impact of chronic heart failure on heart remodeling in patients with atrial fibrillation

Atrial fibrillation (AF) and chronic heart failure (CHF) often coexist due to common pathophysiological mechanisms and risk factors. However, the effect of CHF on heart remodeling in patients with permanent AF has been insufficiently studied. The aim: to study the influence of CHF on changes in structural and geometric parameters and diastolic function of the heart in patients with permanent AF. Materials and methods. The study included 100 patients (men – 60 % (n = 60); women – 40 % (n = 40)) with CHF of ischemic origin and AF, stage II AB, NYHA II-IV FC, and 16 coronary heart disease patients (men – 62.5 % (n = 10), women – 37.5 % (n = 6)) with AF without signs of CHF. Patients were comparable in age (P = 0.267), height (p = 0.406), weight (P = 0.518), body surface area (P = 0.388). Doppler echocardiography was performed on the device Esaote MyLab Eight (Italy) according to standard methods. Results. Patients with AF and signs of CHF were dominated by individuals with eccentric hypertrophy (49 % vs. 19 %; P = 0.0270), and patients with AF without signs of CHF – with eccentric remodeling (0 % vs. 25 %; P = 0.0001). Patients with AF and signs of CHF had significantly higher systolic pressure in the pulmonary artery (54.85 ± 14.23 mm Hg vs. 42.99 ± 11.94 mm Hg; P = 0.028) and pulmonary capillary wedge pressure (PCWP) (12.18 (9.80; 15.33) mm Hg vs. 8.92 (7.62; 10.50) mm Hg; P = 0.005) than patients with AF without signs of CHF, indicating more pronounced pulmonary hypertension and a more significant increase in left atrium pressure. AF patients with signs of CHF demonstrated significantly higher left ventricle end-diastolic pressure (LVEDP), as evidenced by the parameters: E\E’ medial (9.87 ± 5.24 vs. 6.15 ± 1.39; P = 0.001), E/E’ mean (8.38 ± 4.21 vs. 6.06 ± 1.97; P = 0.005), e’ medial (9.96 ± 3.79 cm/s vs. 12.81 ± 3.60 cm/s; P = 0.004). AF patients with signs of CHF had decreased LV EF (55.58 ± 14.65 % vs. 65.44 ± 10.87 %; P = 0.006), systolic velocity of the medial fibrous ring of the mitral valve S (6.92 ± 2.41 cm/s vs. 8.40 ± 2.03 cm/s; P = 0.015), and significantly higher values of TEI RV (0.58 ± 0.16 c. u. vs. 0.48 ± 0.11 c. u.; P = 0.011), but decreased TAPSE values (16.22 ± 4.60 mm vs. 19.54 ± 5.00 mm; P = 0.067), indicating more pronounced systolic dysfunction of both ventricles. Conclusions. Comorbidity of CHF and AF in patients is accompanied by the increased percentage of eccentric hypertrophy (49 %; P = 0.027), more pronounced systolic dysfunction of the left and right ventricles, increased LVEDP, PCWP, systolic pressure in the pulmonary artery, dilation of the inferior vena cava.

Structural and functional changes of the heart in chronic heart failure with preserved left ventricular ejection fraction with excess body weight depending on the presence and form of atrial fibrillation

The aim. To examine the features of structural and functional changes of the heart in patients with chronic heart failure with preserved left ventricular ejection fraction (CHF pr EF) with excess body weight depending on the presence and form of atrial fibrillation (AF). Materials and methods. The study involved 248 patients with CHF pr EF and excess body weight, the mean age was 65.0 ± 11.0 years, 146 females (58.9 %) and 102 males (41.1 %). The first group included 181 patients without concomitant AF, the mean age was 64.0 ± 11.0 years, 110 females (60.8 %) and 71 males (39.2 %); the second group included 67 patients with AF, the mean age was 67.9 ± 11.3 years, 36 females (53.7 %) and 31 males (46.3 %). Subjects with AF were further divided into subgroups: 7 patients with paroxysmal AF, the mean age – 6.7 ± 10.4 years, 3 females (42.9 %) and 4 males (57.1 %), 12 patients with persistent AF, the mean age – 70.8 ± 10.3 years, 10 females (83.3 %) and 2 males (16.7 %); 48 patients with permanent AF, the mean age – 67.3 ± 11.7 years, 23 females (47.9 %) and 25 males (52.1 %). Results. Patients with concomitant AF had a significantly larger aorta diameter (by 3.0 %), systolic left atrium size (LAs) (by 14.5 %), right atrium size (RA) (by 8.3 %), left ventricle end-diastolic size (LVEDS) (by 7.1 %), left ventricle end-systolic size (LVESS) (by 10.6 %), right ventricle size (RV) (by 13,1 %), mean pulmonary artery pressure (by 20.0 %) and the prevalence of LV eccentric hypertrophy (by 21.0 %; P ˂ 0.001). At the same time, LV wall relative thickness (LV RT) was lower by 6.3 %, LV EF – by 3.4 % and the frequency of LV concentric hypertrophy – by 19.1 % (P ˂ 0.001). In permanent form of AF compared to paroxysmal one, significantly larger LAs (by 10.6 %), RA (by 10.9 %), LV myocardial mass (LV MM) (by 18.1 %) and LV MM index (by 21.1 %) were determined and in contrast to persistent AF, LAs (by 9.8 %), RA (by 11.4 %), LVEDS (by 15.6 %), LVESS (by 15.8 %), RV (by 27, 9 %), LV MM (by 29.8 %), LV MMI (by 14.9 %) were predominant, at the same, LVRT was 12.8 % less. Conclusions. In patients with CHF pr EF and excess body weight, concomitant AF is associated with greater dilatation of the heart cavities, eccentric hypertrophy predominance, decreased LV contractility and pulmonary hypertension. Compared to other forms, permanent AF is characterized by severe structural and functional changes in the heart, maximal manifestations of LV dilatation and hypertrophy.

Cardiac remodeling induced by exercise in male master athletes

Aims: To describe cardiac remodeling in a population of male master athletes evaluated by transthoracic echocardiography and to analyse its relationship with several exercise-related characteristics.Methods and results: A total of 105 male master athletes aged ≥40 years old, mostly involved in endurance sports (81.0%) with a median training-volume of 66 [44; 103] METs/h/week, were studied. Left ventricular end-diastolic and end-systolic volumes were above the references in 84.8% and 75.8% athletes, decreasing in frequency when adjusted for BSA (26.3% and 23.2%). LV geometry was changed in more than half of the athletes (eccentric hypertrophy 28.3%, concentric remodelling 15.2% and concentric hypertrophy 8.1%) and several right ventricular (RV) dimensions were increased. Left atrium was dilated in 53.5% and right atrium in 37.4% athletes; only one athlete had a dilated aorta. Mean LV ejection fraction was 61±7% and global longitudinal strain -18.3±2.0%. Changes in LV geometry were more common in high intensity sports; LV dilation in athletes exercising >10 hours/week and in high intensity sports; RV dilation in athletes exercising >66 MET-hour/week and in endurance sports. In multivariate analysis high intensity sports remained an independent predictor of changes in LV geometry. There was a significant correlation between volume of exercise and cardiac structural adaptations.Conclusions: Cardiac structural adaptations were frequent in male master athletes, more pronounced in those involved in endurance sports, with high intensity and high volume of exercise. This data reinforces the concept that the characteristics of exercise are major determinants of cardiac remodeling and should be considered during athletes’ evaluation.