Left Ventricular Morphology Research Articles

Left Atrial Strain is an Independent Determinant of Exercise Capacity in Hypertrophic Cardiomyopathy

Aims: The objective was to evaluate the potential contribution of left atrial (LA) function to reduced exercise capacity in patients with hypertrophic cardiomyopathy (HCM).Methods and results: Using a case-control design we randomly selected 95 patients with confirmed HCM based on guidelines criteria and without permanent atrial arrhythmia who underwent a treadmill exercise test. We measured echo-based left ventricular (LV) and LA morphology and function including mechanics using 2D speckle tracking. Preserved exercise capacity was defined as the 25 th percentile of metabolic equivalents (METs) or > 7 METs. Of 95 HCM patients, 36 had reduced exercise capacity (£7 METs) and 59 had preserved exercise capacity (>7 METs). Reduced exercise capacity patients were more likely to be older, female, had higher BMI, and more advanced heart failure symptoms. They also had a higher E/e’ ratio and lower LA reservoir and conduit strain but similar left ventricular outflow tract (LVOT) pressure gradients. By univariate analysis, LA reservoir and conduit strain, age, gender, BMI, NYHA class, and E/e’ correlated with METs. In multivariate analysis, LA conduit strain independently determined METs after adjusting for age, gender, BMI, NYHA and E/e’ (standardized coefficients 0.17, P=0.04). This relationship was primarily noted in non- and labile-obstructive but not in obstructive HCM. History of atrial fibrillation did not impact the association of LA strain with exercise capacity.Conclusion : Even after adjusting for LVOT gradients and diastolic function, reduced LA conduit strain is an independent determinant of exercise tolerance in HCM.

Abstract 10496: Cardiac Function in Postmenopausal Women Are Unaltered by Two Decades of Different Physical Activity Levels

Rationale: In women, the risk of coronary heart disease increases significantly after the onsetof menopause. Exercise and active lifestyle have known benefits such as a significantly reducedrisk of heart failure. To date, most of the knowledge on physical activity induced changes incardiac function in older individuals are based on males and with a sparsity of data from healthypostmenopausal women with differing physical activity and fitness. Aim: The aim was to determine the impact of more than twenty years of differing physicalactivity levels and maximal oxygen consumption on cardiac morphology and function inpostmenopausal women. Method: The study design was cross-sectional with age-matched non-smoking, non-medicatedhealthy women divided in to three groups based on their self-reported physical activity levelwith regard to intensity and volume over the past two decades. Forty-one women was included(age of 61 ± 1 years; 11 ± 2 postmenopausal years; body mass index 23 ± 3 kg • m 2 ) and dividedinto groups based on activity level categorized as sedentary (SED; ≤1 h exercise weekly; n=14);Moderate (MOD; ≥2 ≤6h low/moderate intensity exercise weekly; n=12) and high (HIGH; <4h of moderate/high intensity exercise weekly; n=15). Cardiac function and dimensions wereassessed with transthoracic echocardiography and maximal pulmonary oxygen uptake wasdetermined by graded bike ergometer exercise to exhaustion. Results: The three groups displayed significantly different levels of maximum oxygen uptake(24.9 ± 5.8; 30.5 ± 5.8; 38.4 ± 4.4 ml/kg, for SED, MOD and HIGH respectively) (p < 0.01).No differences were observed in resting left ventricular (LV) morphology (LVmass, LVmassindex) systolic function (EF%, GLS and mitral valve S′), diastolic function (E/A ratio, IVRT)or right ventricular function (TAPSE and tricuspid annular velocity S’) between the threegroups. Conclusions: These data show that the level of lifelong physical activity and correspondingdifferences in maximal oxygen consumption, may have less impact on left ventricularmorphology and systolic/diastolic function in healthy postmenopausal women than previouslyexpected.

Abstract 12644: Clinical Features and Outcomes by Systemic Ventricle Morphology in Adult Fontan Patients

Introduction: Single ventricle physiology is commonly encountered in patients after Fontan palliation. However, limited data exists on the differences in clinical characteristics and long-term outcomes in adults with systemic left ventricular morphology (SLV) compared to systemic right ventricular morphology (SRV). Methods: Retrospective review of medical records from a tertiary medical center for 2010-2018 identified 191 Fontan patients ≥ 18 years of age for whom ventricular morphology data was available. Results: Of 191 patients, 62 (32%) had SRV and 129 (68%) had SLV. Mean age was 28.9 ± 9.1 years and mean age at the time of Fontan palliation was 6.4 ± 6.7 years. Patients with SLV were older (30.9 ± 9.6 years vs. 24.7 ± 6.0 years) and more likely to have classic atriopulmonary connection (17% vs. 2%). Differences in adverse outcomes by ventricular morphology are shown in the figure. After adjusting for age, patients with SRV were more likely to have atrioventricular valve regurgitation (adjusted odds ratio 3.42, 95% confidence interval 1.56-7.52, p=0.002). There were no significant age-adjusted differences between SRV and SLV patients for NYHA class, arrhythmia/pacemaker placement/implantable cardioverter-defibrillator (ICD) placement, heart failure hospitalization, thromboembolic complications, cirrhosis, protein-losing enteropathy, Fontan revision, or death. Data from cardiac catheterization, cardiopulmonary exercise testing, and liver function tests showed no significant differences. Conclusion: Adverse outcomes among adult recipients of the Fontan procedure did not differ significantly based on ventricular morphology. Further multicenter studies will be necessary to understand finer differences in SRV and SLV pathophysiology and eventually the impact of ventricular modeling on long term outcomes as the adult Fontan population continues to age.

Compound Mutation in Cardiac Sarcomere Proteins Is Associated with Increased Risk for Major Arrhythmic Events in Pediatric Onset Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is associated with adverse left ventricular (LV) remodeling causing dysfunction and malignant arrhythmias. Severely affected patients present with disease onset during childhood and sudden cardiac death risk (SCD) stratification is of the highest importance in this cohort. This study aimed to investigate genotype–phenotype association regarding clinical outcome and disease progression in pediatric onset HCM. Medical charts from forty-nine patients with pediatric HCM who had undergone genetic testing were reviewed for retrospective analysis. Demographic, clinical, transthoracic echocardiographic, electrocardiographic, long-term electrocardiogram, cardiopulmonary exercise test, cardiac magnetic resonance, and medication data were recorded. Childhood onset HCM was diagnosed in 29 males and 20 females. Median age at last follow-up was 18.7 years (range 2.6–51.7 years) with a median follow-up time since diagnosis of 8.5 years (range 0.2–38.0 years). Comparison of patients carrying mutations in distinct genes and comparison of genotype-negative with genotype-positive individuals, revealed no differences in functional classification, LV morphology, hypertrophy, systolic and diastolic function, fibrosis and cardiac medication. Patients with compound mutations had a significantly higher risk for major arrhythmic events than a single-mutation carrier. No association between affected genes and disease severity or progression was identified in this cohort.

Left ventricular vortex analysis by high-frame rate blood speckle tracking echocardiography in healthy children and in congenital heart disease.

High-frame rate blood speckle tracking (BST) echocardiography is a new technique for the assessment of intracardiac flow. The purpose of this study was to evaluate the characteristics of left ventricular (LV) vortices in healthy children and in those with congenital heart disease (CHD). Characteristics of LV vortices were analyses based on 4-chamber BST images from 118 healthy children (median age 6.84years, range 0.01-17years) and 43 children with CHD (median age 0.99years, range 0.01-14years). Both groups were compared after propensity matching. Multiple linear regression was used to identify factors that independently influence vortex characteristics. Feasibility of vortex imaging was 93.7% for healthy children and 95.6% for CHD. After propensity matching, there were no overall significant differences in vortex distance to apex, distance to interventricular septum (IVS), height, width, sphericity index, or area. However, multiple regression analysis revealed significant associations of LV morphology with vortex characteristics. Furthermore, CHD involving LV volume overload and CHD involving LV pressure overload were both associated with vortices localized closer to the IVS. LV vortex analysis using high-frame rate BST echocardiography is feasible in healthy children and in those with CHD. As they are associated with LV morphology and are modified in some types of CHD, vortices might yield diagnostic and prognostic value. Future studies are warranted to establish applications of vortex imaging in the clinical setting.

Left ventricular strain-curve morphology to distinguish between constrictive pericarditis and restrictive cardiomyopathy.

AimsTo distinguish between constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM) using cardiac magnetic resonance feature tracking (CMR‐FT) left ventricle (LV) diastolic time–strain curve patterns and myocardial strain.Methods and ResultsA total of 32 CP patients, 27 RCM patients, and 25 control subjects were examined by CMR‐FT and analysed for global strain, segmental strain, and LV time–strain curve patterns in the longitudinal, circumferential, and radial directions. Speckle tracking echocardiography (STE) strain imaging was performed in some cases. The peak global longitudinal strain (GLS) and global circumferential strain (GCS) of the RCM group were lower than those of the CP group. GLS [median (interquartile range) CP vs. RCM: −11.15 (−12.85, −9.35) vs. −6.5 (−8.75, −4.85), P < 0.001] and GCS (CP vs. RCM: −16.89 ± 5.11 vs. −13.37 ± 5.79, P < 0.001). In circumferential and radial directions, the strain ratios of the LV lateral/septal wall (LW/SW) of the CP group were significantly lower than those of the RCM group at the basal and mid segments. The CS ratio of LW/SW at the basal segment [CP vs. RCM: 0.95 (0.85, 1.25) vs. 1.43 (1.18, 1.89), P < 0.001] and mid segment [CP vs. RCM: 1.05 (0.92, 1.15) vs. 1.18 (1.06, 1.49), P = 0.026]. The RS ratio of LW/SW at the basal segment [CP vs. RCM: 0.97 (0.76, 1.37) vs. 1.55 (1.08, 2.31), P = 0.006] and mid segment [CP vs. RCM: 0.95 (0.70, 1.28) vs. 1.79 (1.32, 2.92), P < 0.001]. In the longitudinal and circumferential directions, the characteristic ‘plateau’ pattern of time–strain curves could be seen in the CP but not in the RCM during the diastole. The GCS ratio of 0–50%/50–75% diastolic period of the CP was higher than that of the RCM [CP vs. RCM: 17.01 (8.67, 23.75) vs. 5.38 (1.93, 11.24), P = 0.001], while the GCS ratio of 50–75%/75–100% diastolic period was lower than that of the RCM [CP vs. RCM: 0.36 (0.15, 1.67) vs. 1.12 (0.70, 5.58), P < 0.001]. The peak GLS (sensitivity, 85%; specificity, 78%) and the GCS ratio of 0–50%/50–75% diastolic period (sensitivity, 88%; specificity, 73%) had higher differential diagnosis value.ConclusionsThe CMR‐FT could distinctly differentiate CP from RCM based on LV myocardial strain and LV time–strain curve patterns. The characteristic ‘plateau’ pattern of the time–strain curve is specific for CP and not RCM and this curve can also be duplicated by STE.

Phenotyping the right heart according to left ventricular geometry patterns in severe HFrEF

Abstract Background Right ventricular (RV) failure significantly impact on heart failure with reduced ejection fraction (HFrEF) prognosis. How and whether specific functional and geometrical phenotypes of the RV function adapt and combined with left ventricular (LV) geometry is unknown. Purpose To test the RV function across LV geometrical patterns looking at respective prognostic roles. Methods We retrospectively examined a population of patients homogenously diagnosed with chronic HFrEF (defined as LV ejection fraction (EF) less than 35%) and treated with optimal therapy (OT) and all implanted with ICD for primary prevention of sudden cardiac death. Patients were categorized by echocardiography according to remodeling pattern based on left ventricular mass index and relative wall thickness into four groups: normal geometry (NG), concentric remodeling (CR), concentric hypertrophy (CH) and eccentric hypertrophy (EH). RV parameters were: tricuspid annulus plane systolic excursion (TAPSE), TAPSE/pulmonary artery pressures (PAPs), RV basal diameter and fractional area change (FAC). Outcome variable was all-cause mortality, assessed with multivariable Cox proportional hazard (PH) models. Results Among 193 patients (age 66±11 years, 81% men, 74% with ischemic etiology of HF and EF 28±5%) 21% had NG, 3% had CR, 8% had CH, and 68% had EH. Distribution of RV echo parameters across LV remodeling groups is shown in table 1. Over a median follow-up time of 4 (1.9 – 6.1) years, 65 deaths occurred. In multivariable Cox PH models adjusted for age, LVEF, ischemic etiology and LV geometry, TAPSE, TAPSE/PAPs, RV basal diameter and FAC strongly and independently predicted the outcome variable [HR 0.92 (95% C.I. 0.86–0.98), HR 0.08 (95% C.I. 0.01–0.57), HR 1.87 (95% C.I. 1.29–2.71), HR 0.97 (95% C.I. 0.95–1.00), respectively all p-value &amp;lt;0.05]. Conclusion In a homogeneously defined population of severe HFrEF outpatients receiving OT, the majority showed EH remodeling pattern, which did not predict the primary outcome. LV geometry did not further stratify patients in this high risk group. Conversely, RV dysfunction proved to be a strong predictor of mortality, independently of age, LV function and etiology of HF, regardless LV morphology. Funding Acknowledgement Type of funding sources: None.

Different myocardial microRNA expression patterns are observed in pressure overload- and volume overload-induced chronic heart failure

Abstract Introduction MicroRNAs (miRNA) are short, single-stranded non-coding RNA molecules that regulate gene expression on the post-transcriptional level. Dysregulation of distinct miRNAs has been found to contribute to the development of chronic heart failure (CHF). However, whether distinct types of CHF are associated with different miRNA expression patterns is debated. Aim To characterize left ventricular (LV) miRNA expression in rat models of pressure overload (PO) versus volume overload (VO)-induced CHF. Methods Transverse aortic constriction (TAC) was performed to evoke PO-induced CHF. Aortocaval fistula (ACF) was created to establish VO-induced CHF. Age-matched sham-operated rats served as controls for TAC (ShamT) and ACF (ShamA), respectively. Pressure-volume analysis, echocardiography, histology and quantitative real-time PCR were carried out to assess alterations of the LV. Global miRNA expression profiling was performed using Nanostring technology. Bioinformatics analysis of differentially expressed miRNAs was also carried out to predict relevant miRNA-target interactions. Results Reduced LV systolic function (ejection fraction: 38±5 vs. 65±2% TAC vs. ShamT, 55±3 vs. 67±3%, ACF vs. ShamA, P&amp;lt;0.01) as well as elevated myocardial B-type natriuretic peptide and increased β-to-α myosin heavy chain gene expression confirmed the development of pathological remodeling and CHF in both models. Nevertheless, characteristic differences could be observed in LV morphology and ultrastructure. Accordingly, the TAC model was associated with robustly increased wall thickness, concentric LV hypertrophy and marked fibrotic remodeling. On the contrary, LV dilatation, eccentric LV hypertrophy and moderate fibrosis were the main morphometric findings in the ACF model. A group of miRNA (rno-miR-130a, 132, 199a-5p, 21, 210, 27b, 326) showed similar alterations in both phenotypes of CHF. However, other miRNAs demonstrated unique (specific to TAC: rno-miR-148b-3p, 150, 199a-3p, 203, 23b, 27b, let-7e; specific to ACF: rno-miR-140, 142-3p, 17-5p, 195, 20a, 204, 214, 27a, 29b, 322, 365, 425, 450a, let-7i) LV expressional changes in distinct phenotypes of CHF. In silico bioinformatics analysis revealed that the altered miRNA expression pattern predominantly controls the cardiac neural crest cell development, the inositol-phosphate pathway and the expression of microtubules-binding proteins. In contrast, alterations in the expression of genes responsible for redox state and epithelial-mesenchymal transition were modified only in the ACF group. Despite of the different signaling cascades, expression of Arhgap12 (Rho GTPase activating protein 12) was predicted to be strongly inhibited in both CHF models. Conclusions PO and VO-induced CHF are associated with unique miRNA expression patterns, which drive different signaling pathways. miRNA-controlled downregulation of Arhgap12 might represent a common feature in both phenotypes of CHF. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): ÚNKP-20-4-II-SE-20/New National Excellence Program of the Ministry of Human CapacitiesNVKP_16-1–2016-0017 (“National Heart Program”) National Research, Development and Innovation Fund of Hungary

Left ventricular outflow morphology as a predictor of arrhythmic disturbances after TAVI

Abstract Introduction Left bundle branch block (LBBB) and permanent pacemaker (PM) are frequent complications after transcatheter aortic valve implantation (TAVI), but few predictors have been reported. Purpose This study sought to determine the relationship between left ventricular outflow tract (LVOT) morphology and the development of conduction disturbances after TAVI. Methods From 1/2020 to 12/2020 consecutive patients who underwent TAVI and an analyzable CT scan in our center were selected. Patients were categorized according to the LVOT morphology into three groups. The delta value between mean aortic root diameter (AA-d) and mean LVOT-d were calculated, and divided into terciles. In patients in the third tercile the AA-d was greater than LVOT-d and was defined as tapered-LVOT (group 1). First and second terciles had tubular or flared-LVOT shape and were defined as group 2. We compared conductance disorders after TAVI with and without tapered-LVOT. Primary endpoint was the combined of new-onset of transient/persistent LBBB, and PM. Factors with p&amp;lt;0.05 on the univariate analysis were entered into the multivariate analysis. Results Among 98 eligible patients thirty-two patients (33%) presented a tapered-LVOT (Group 1) and 66 (67%) had tubular or flared-LVOT morphology (group 2). The mean age was 80.5±5.5 years and 60% were female. Baseline characteristics were similar between groups except for the incidence of dyslipidemia that was higher in group 2. The primary study endpoint was significantly higher in group 1 (78% vs. 59%: p=0.036). After adjusting for confounding factors, this relationship remained statistically significant (OR: 2.81 (CI95%: 1–7.96), p 0.046). Independent predictors of conduction disturbance were: tapered-LVOT, prior coronary artery disease and prior surgical valve replacement. Conclusions After TAVI, patients presenting a tapered-LVOT morphology have a 2.8-fold greater risk to develop LBBB or require permanent PM when compared to another LVOT shapes. Funding Acknowledgement Type of funding sources: None.

Effect of migalastat on cardiac involvement in Fabry disease: preliminary results from MAIORA study

Abstract Background Fabry Disease (FD) is a rare X-linked lysosomal storage disorder. Since 2016, pharmacological chaperone Migalastat has been approved for treatment of FD patients with amenable mutations to stabilize defective forms of the enzyme α-galactosidase A. A small but significant reduction in left ventricular (LV) mass after 18 months of Migalastat treatment has been previously reported by echocardiography. However, an integrated assessment of the effect of Migalastat on cardiac involvement, combining LV morphology and tissue composition by CMR with exercise capacity by cardiopulmonary test, is lacking. Purpose To determine the effects of 18 month treatment with Migalastat on LV mass, native T1 value and functional capacity in naïve patients with genetically confirmed FD cardiomyopathy. Methods Sixteen treatment naïve FD patients (4 females, mean age 46.4±16.2) with amenable mutations and signs of cardiac involvement underwent CMR with T1 mapping and cardio-pulmonary testing before and after 18 months of migalastat therapy as a part of MAIORA Study. Cardiac involvement was defined as presence of reduced native T1 values at CMR (a surrogate of myocardial glycosphingolipid storage) and/or LV hypertrophy (LVH). Nine patients (56%, 2 females, mean age 56.4±12.7 years) had LVH at baseline. Results Migalastat treatment was well tolerated in all patients, with no serious adverse event. No change in LV mass was detected at 18 months compared to baseline (95.2 (66.0–184.0) vs 103.0 (71.0–182.0) g/m2; p=0.5516). The same result was found after stratifying patients according to presence/absence of Late Gadolinium Enhancement (LGE) (LGE+ n=8, 2 females, mean age 56.2±13.1 years). There was a trend towards an increased native septal T1 value (870.0 (848–882) vs 860.0 (833.0–875.0) ms at baseline; p 0.056) with unchanged extracellular volume (ECV) (0.26 (0.23–0.028) vs 0.26 (0.22–0.29) at baseline; p 0.276) in the overall cohort. An improvement in functional capacity with a trend towards an increase in percent-predicted peak VO2 (72.0 (61.25–80.75) vs 67.0 (45.2–79.2) at baseline; p 0.056) and a significant increase in VO2 at anaerobic threshold (14.8 (12.6–20.0) vs 13.10 (6.8–18.6) ml/kg/min at baseline; p 0.004) was reported in the total population. Conclusion In treatment naïve FD patients with amenable mutations and signs of early or overt cardiac involvement, 18-month treatment with Migalastat stabilized LV mass both in patients with and without LGE and was associated with an improvement in exercise tolerance. The trend towards an increase in T1 value associated with unchanged ECV suggests partial clearance of cardiomyocyte glycoshingolipid storage. These real-world data are consistent with a beneficial impact of migalastat on the progression of cardiac involvement in FD. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Amicus Therapeutics

VP22.23: Fetal complex rare cardiac malformation

A 27-year-old gravida 1 para 0 attended for anomaly scan with a singleton pregnancy. There were no significant events of interest nor consanguinity between both parents. Second-trimester ultrasound scan at 22+3 weeks showed a single live fetus in changing lie. Fetal Echo revealed: Situs solitus. The 4- chamber view showed univentricular heart, left handed ventricular topology, right sided main ventricle of left ventricular morphology, hypoplastic left sided (morphological right) ventricle, left sided AV valve (likely tricuspid valve) atresia, VSD (subaortic), AV & VA discordance - congenitally corrected transposition. Foramen ovale was largely restrictive with significant a-wave reversal. Aorta was located to right and anterior to pulmonary artery - D malposition. Aortic arch hypoplasia, mild preductal aortic coarctation, main pulmonary arterial dilatation, bilateral branch pulmonary artery origin stenosis was noted. No arrhythmias, no disturbances in the heart rate. Fetal cardiac function was normal. Amniocentesis and microarray offered but refused by patient. At 39+3 weeks of gestation a 3.05 kg male infant was born by spontaneous vaginal delivery, required PPV and CPAP at birth, due to poor respiratory effort then recovered. Postnatal echocardiography confirmed the diagnosis and on second day after birth the newborn underwent Norwood surgery with right modified Blalock-Taussig shunt and recovered uneventfully. The second stage surgery (Glenn superior cavo pulmonary shunt) and PA plasty was performed at 6 months of age and the patient recovered uneventfully. The patient will be followed in multidisciplinary fashion along with pediatric cardiac critical care and pediatric cardiology teams. He will proceed along the univentricular pathway, with a Fontan procedure (at a weight of 15 kg or greater) at 3 to 4 years of age, preceded by cardiac catheterisation. He should remain on aspirin (5 mg/kg once daily) until his Fontan (if feasible).

Abstract MP237: Multi-omics Profiling Reveals Stearoylcarnitine As A Novel Biomarker Of Cardiometabolic Disease Development In Rat Offspring Exposed To Gestational Diabetes

Through unknown mechanisms, fetal exposure to gestational diabetes mellitus (GDM) increases the risk for cardiovascular disease development later in life. We hypothesize that fetal exposure to GDM alters offspring cardiomyocyte metabolism and left ventricular (LV) function with age. To induce GDM, female rats were fed a high fat (45% kcal) and sucrose diet prior to mating, throughout pregnancy and lactation. Lean controls received a low fat (10% kcal) diet. Fetal rat ventricular cardiomyocytes (FRVC) were isolated from e20 offspring for U-13C glucose metabolic flux analysis, mitochondrial respiration and calcium handling. The cardiac transcriptome and metabolome were measured in 3-month old offspring. LV morphology and function was assessed in the offspring from e18 to 12-months of age by transthoracic ultrasound. Offspring exposed to GDM exhibited increased LV posterior wall thickness and impaired LV filling across their life course (fetal to 12-months of age; p&lt;0.05). Consistent with the development of diastolic dysfunction in vivo, alterations in calcium flux and sarcoplasmic reticulum-dependent calcium re-uptake (1.5 and 1.6-fold greater, respectively) were observed in FRVC isolated from GDM offspring (p&lt;0.05). When FRVC were treated with isoproterenol, U-13C glucose metabolic flux through glycolysis and the citric acid cycle was reduced in GDM offspring, compared to Lean controls. In 3-month old GDM offspring serum and cardiac metabolomics revealed an altered acylcarnitine profile, with specific elevation in long chain acylcarnitine species including stearoylcarnitine. Alterations in the metabolome corresponded to changes in gene expression patterns identified by RNA-Seq associated with glucose metabolism and fatty acid transport pathways (e.g. Irs2, Slc2a4, Pfkfb2, Pdk4 and Cpt1a). These alterations corresponded with mitochondrial dysfunction, impaired cardiomyocyte metabolic flux and contractility, in concert with LV hypertrophy and diastolic dysfunction in the rat offspring. Multi-omics profiling reveals stearoylcarnitine as a novel biomarker and implicates mitochondrial oxidative metabolism as a mechanism that links early-life GDM exposure to the development of cardiovascular disease later in life.

Anomalous origin of left main coronary artery from pulmonary artery: Patient characteristics and imaging associations on multidetector computed tomography angiography.

To evaluate the various imaging features and associations on multidetector computed tomography (CT) angiography in patients with anomalous origin of left main coronary artery (LMCA) from pulmonary artery (ALCAPA). We retrospectively reviewed multidetector CT angiography studies done for the evaluation of congenital heart diseases at our institution through 2014 to 2021. Cases with ALCAPA were identified and relevant history and imaging findings including the origin of coronary arteries, left ventricular (LV) morphology and functions, intercoronary collaterals, and associated abnormalities were evaluated. Twelve patients (eight males,three adults, and nine children; age range: 2 months to 54 years) with ALCAPA were included. Gradually progressive dyspnea and failure to thrive (6/9; 66.67% each) were the most common symptoms amongchildren, whereas adults were commonly asymptomatic (2/3; 66.67%). The LMCA was originating from pulmonary sinus, main, and right pulmonary artery in 6 (50%), 5 (41.66%), and 1 (8.3%) patients, respectively. In adult-type ALCAPA, right coronary artery (RCA), left anterior descending artery (LAD), and left circumflex artery (LCx) were dilated and tortuous, with the presence of well-developed intercoronary collaterals and preserved LV ejection fractions; these features were not seen in patients of infantile ALCAPA. LV dysfunction with global hypokinesia was the most common wall motion abnormality (7/12; 58.33%). Degree of collateralization could be the key factor determining the time of presentation, clinical symptoms, and LV function, thus influencing clinical outcomes. Patients with infantile ALCAPA present with features of heart failure and have dilated and dysfunctional LV consequent to lack of collaterals, unlike adult-type ALCAPA.

Biventricular Morphology and Function Reference Values Derived From a Large Sample of Healthy Chinese Adults by Magnetic Resonance Imaging.

Background: Quantification of cardiac structure and function is essential for diagnostic interpretation and clinical decision making. We sought to establish cardiovascular magnetic resonance (CMR) reference values of left and right ventricular (LV and RV) morphology and function based on a large sample of healthy Chinese adults.Methods: Five hundred fifty validated healthy Chinese adults (aged 21–70 years; 323 men) free of hypertension, diabetes, and obesity were included in this study. All the subjects were stratified by gender (men and women) and age decades. On cine CMR, measurements of biventricular end-diastolic, end-systolic, and stroke volumes (EDV, ESV, and SV), ejection fraction (EF), and end-diastolic LV wall thickness (LVWT) and mass (LVM) were obtained.Results: Men had greater LVEDV (111.6 ± 19.8 vs. 94.6 ± 15.6 ml), LVESV (36.5 ± 9.8 vs. 28.2 ± 7.9 ml), LVM (121.1 ± 19.9 vs. 86.1 ± 14.5 g), global end-diastolic LVWT (8.1 ± 1.1 vs. 6.7 ± 1.0 mm), RVEDV (128.0 ± 23.6 vs. 101.7 ± 17.0 ml), and RVESV (53.5 ± 13.7 vs. 36.8 ± 8.9 ml), while women had greater LVEF (67.5 ± 5.4 vs. 70.4 ± 5.7%) and RVEF (58.5 ± 5.2 vs. 64.0 ± 5.3%) (all p < 0.001). For both men and women, age was negatively correlated with LVEDV (r = −0.31 and r = −0.32), LVESV (r = −0.37 and r = −0.47), RVEDV (r = −0.31 and r = −0.29), and RVESV (r = −0.33 and r = −0.44), while it was positively correlated with LVEF (r = 0.28 and r = 0.43) and RVEF (r = 0.28 and r = 0.41) (all p < 0.001). Aging was associated with increasing global end-diastolic LVWT and LVM/LVEDV in both sexes (all p < 0.001). Older age was associated with increasing LVM only in women (r = 0.36, p < 0.001), not in men (r = 0.05, p = 0.359).Conclusions: We systematically provide age-, sex-, and body size-specific CMR reference values for biventricular morphology and function based on a large sample of healthy Chinese adults. Biventricular structure and function are significantly associated with age and sex.

Whole-Heart High-Resolution Late Gadolinium Enhancement: Techniques and Clinical Applications.

In cardiovascular magnetic resonance, late gadolinium enhancement (LGE) has become the cornerstone of myocardial tissue characterization. It is widely used in clinical routine to diagnose and characterize the myocardial tissue in a wide range of ischemic and nonischemic cardiomyopathies. The recent growing interest in imaging left atrial fibrosis has led to the development of novel whole‐heart high‐resolution late gadolinium enhancement (HR‐LGE) techniques. Indeed, conventional LGE is acquired in multiple breath‐holds with limited spatial resolution: ~1.4–1.8 mm in plane and 6–8 mm slice thickness, according to the Society for Cardiovascular Magnetic Resonance standardized guidelines. Such large voxel size prevents its use in thin structures such as the atrial or right ventricular walls. Whole‐heart 3D HR‐LGE images are acquired in free breathing to increase the spatial resolution (up to 1.3 × 1.3 × 1.3 mm3) and offer a better detection and depiction of focal atrial fibrosis. The downside of this increased resolution is the extended scan time of around 10 min, which hampers the spread of HR‐LGE in clinical practice. Initially introduced for atrial fibrosis imaging, HR‐LGE interest has evolved to be a tool to detect small scars in the ventricles and guide ablation procedures. Indeed, the detection of scars, nonvisible with conventional LGE, can be crucial in the diagnosis of myocardial infarction with nonobstructed coronary arteries, in the detection of the arrhythmogenic substrate triggering ventricular arrhythmia, and improve the confidence of clinicians in the challenging diagnoses such as the arrhythmogenic right ventricular cardiomyopathy. HR‐LGE also offers a precise visualization of left ventricular scar morphology that is particularly useful in planning ablation procedures and guiding them through the fusion of HR‐LGE images with electroanatomical mapping systems. In this narrative review, we attempt to summarize the technical particularities of whole‐heart HR‐LGE acquisition and provide an overview of its clinical applications with a particular focus on the ventricles.Evidence Level2Technical Efficacy Stage2

Network analysis of the left anterior descending coronary arteries in swim-trained rats by an in situ video microscopic technique

BackgroundWe aimed to identify sex differences in the network properties and to recognize the geometric alteration effects of long-term swim training in a rat model of exercise-induced left ventricular (LV) hypertrophy.MethodsThirty-eight Wistar rats were divided into four groups: male sedentary, female sedentary, male exercised and female exercised. After training sessions, LV morphology and function were checked by echocardiography. The geometry of the left coronary artery system was analysed on pressure-perfused, microsurgically prepared resistance artery networks using in situ video microscopy. All segments over > 80 μm in diameter were studied using divided 50-μm-long cylindrical ring units of the networks. Oxidative-nitrative (O-N) stress markers, adenosine A2A and estrogen receptor (ER) were investigated by immunohistochemistry.ResultsThe LV mass index, ejection fraction and fractional shortening significantly increased in exercised animals. We found substantial sex differences in the coronary network in the control groups and in the swim-trained animals. Ring frequency spectra were significantly different between male and female animals in both the sedentary and trained groups. The thickness of the wall was higher in males as a result of training. There were elevations in the populations of 200- and 400-μm vessel units in males; the thinner ones developed farther and the thicker ones closer to the orifice. In females, a new population of 200- to 250-μm vessels appeared unusually close to the orifice.ConclusionsPhysical activity and LV hypertrophy were accompanied by a remodelling of coronary resistance artery network geometry that was different in both sexes.

Percutaneous Mitral Valve Annuloplasty in Patients With Secondary Mitral Regurgitation and Severe Left Ventricular Enlargement

ObjectivesThis study sought to determine the effect of percutaneous mitral valve annuloplasty with the Carillon device versus guideline-directed medical therapy (GDMT) alone in patients with secondary mitral regurgitation (MR) and severe left ventricular (LV) enlargement. BackgroundThe clinical impact of the Carillon device in patients with severe LV dilation is not well established. MethodsThis is a pooled analysis involving 3 prospective trials (TITAN [Transcatheter Implantation of Carillon Mitral Annuloplasty Device], TITAN II, and REDUCE FMR [CARILLON Mitral Contour System for Reducing Functional Mitral Regurgitation] trials) in which patients with functional MR and severe LV enlargement (LV end-diastolic diameter >65 mm) were treated with GDMT and the Carillon device versus GDMT alone. Key outcomes of this analysis were changes over 1 year of follow-up in mitral valve and LV echocardiographic parameters, functional outcome, quality of life, mortality, and heart failure hospitalization (HFH). ResultsA total of 95 patients (67 in the Carillon group, 28 in the GDMT group) with severe LV enlargement were included. In the Carillon group, all mitral valve and LV morphology parameters were significantly improved at 1 year. Regurgitant volume decreased by 12 ml (p < 0.001), MR grade decreased by 0.6 U (p < 0.001), LV end-diastolic volume decreased by 25 cm3 (p = 0.005), and LV end-systolic volume decreased by 21 cm3 (p = 0.01). Significant functional improvement differences were also noted between the Carillon group and the GDMT group including an improvement of Kansas City Cardiomyopathy Questionnaire score (15 ± 4 vs. 6 ± 6; p = 0.03). The incidence of HFH was 29.9% versus 50.0% and the cumulative rate of HFH was 0.43 versus 0.75 (p < 0.001). ConclusionsIn patients with functional MR and severe LV enlargement, the Carillon device improved mitral valve function, LV morphology, and functional outcome compared with patients receiving GDMT only. Preoperative LV dimension should not be a limiting factor when evaluating patient eligibility or anticipated response to therapy with the Carillon device.

476 Sleep-Disordered Breathing is More Predictive than Obesity of Increased Left Ventricular Mass Index in Bariatric Surgery Patients

Abstract Introduction Obesity and obstructive sleep apnea (OSA) are associated with left ventricular hypertrophy and increased cardiovascular risk. Alternatively, the “obesity paradox” describes an improved prognosis from heart failure in obesity, though potentially attributable to confounding/bias. We sought to determine the contributions of obesity and sleep-disordered breathing (SDB) to left ventricular function and morphology in bariatric surgery candidates. Methods Patients undergoing polysomnography prior to bariatric surgery from 2011–2018 had demographic (age, gender, race), anthropometric (body mass index [BMI], neck circumference), comorbidities (atrial fibrillation, coronary artery disease, diabetes, hypertension, hyperlipidemia), echocardiographic and sleep-disordered breathing (apnea-hypopnea index [AHI], peak end-tidal CO2 [etCO2]) variables retrospectively examined. The echocardiographic visit closest to polysomnogram within two years was selected with missing values filled by available values within 6 months. Linear regression assessed the relationship of BMI, AHI, and etCO2 with left ventricular mass index (LVMI) after adjustment of demographics and comorbidities. Echocardiographic measures were logarithm transformed before regression analysis. Coefficients and 95% confidence intervals (CI) were calculated by exponential transformation. The analysis was performed based on an overall significance level of 0.05 using SAS software (version 9.4, Cary, NC). Results The total of 832 patients had 24% males, mean age 48.8±12, 60% white, and BMI:49.4±9.5kg/m2. Ejection fraction (%) was 60.0±7.0, and LVMI (g/m2): 80.9±23.7. In adjusted models, LVMI decreased by 2.1% for each 5kg/m2 increase in BMI (coefficient=0.979, 95%CI 0.961–0.997, p=0.022) and increased by 4.3% for each 5 mmHg increase in etCO2 (coefficient=1.043, 95%CI 1.013–1.073, p=0.005). Without adjustment, patients with AHI ≥ 5 had 15.3% higher LVMI than non-OSA group (coefficient=1.153, 95%CI 1.034–1.286, p=0.011) and moderate/severe OSA was associated with a 7.6% higher LVMI than those with AHI&amp;lt;15 (coefficient 1.076, 95%CI 1.003–1.153, p=0.040), but not statistically significant after adjustment. Conclusion In obese patients, nocturnal hypoventilation rather than obesity may have adverse influences on left ventricular morphology. Future studies should focus on clarifying whether obesity is truly protective in terms of LV mass, i.e. reflective of paradox versus a product of bias. The potential benefit of identifying/treating SDB in bariatric surgery candidates to mitigate cardiovascular risk also deserves further investigation. Support (if any) Cleveland Clinic Transformative Resource Neuroscience Award

A comparative study of left ventricular function during pregnancy without and with gestational hypertension and gestational diabetes mellitus

The use of nanoscale ultrasonic contrast agent greatly improved the reliability of ultrasonic technology detection, and it became an effective tool to detect a series of diseases. Gestational hypertension and Gestational Diabetes Mellitus (GDM) are unique and common complications during pregnancy, and they seriously affect women’s postnatal health. In this study, we evaluated the practical value of echocardiogram in evaluating Left Ventricular (LV) morphology and function changes during pregnancy with gestational hypertension and GDM. 46 pregnant women with gestational hypertension and GDM as disease group and 50 healthy pregnant women as normal group were included in the study. By echocardiogram analysis, the morphology, systole and diastole functions of LV were compared in both groups. With LV morphology change during pregnancy, LA volume (P = 0.011) of disease group was bigger than that of normal group and LV mass (P &lt; 0.0001) and LVMi (P &lt; 0.0001) of disease group were higher than that of normal group. However, the LVPWd (P &lt; 0.0001) and IVSd (P &lt; 0.0001) of disease group thickened clearly relative to that of the normal group. However, these values, including LVIDd (P = 0.185), EF value (P = 0.779), FS value (P = 0.740) and Cardiac Index (P = 0.444) for their cardiac LV systolic functions of two groups, had very few large-scale differences. Compared to normal pregnant cardiac, the E value (P = 0.014) was lower and the A value (P &lt; 0.0001) was higher in the disease group. Moreover, E/A ratio (P &lt; 0.0001) was obviously less than that in the experimental. According to TDI measures for both groups, the E’ value (P &lt; 0.0001) and ratio of E/A’ (P &lt; 0.0001) were lower and A’ value (P = 0.003) was slightly higher in the disease group compared with normal group. In recent years, we found that the E/E’ value (P = 0.0002) in the disease group was also higher. In summary, LV diastolic function during pregnancy with complications changes pregnant LV morphology and function. Echocardiogram can be used for testing and monitoring these changes as one of simple and reliable inspection methods.

BNP LEVELS AND LEFT VENTRICULAR MORPHOLOGY AND FUNCTION IN HYPERTENSIVE PATIENTS BEFORE AND AFTER AN INTRAVENOUS SALINE LOAD

Objective: Previous studies have reported a relationship between BNP levels and left ventricular (LV) morphology and function in essential hypertension (EH), but results are conflicting. The aim of the study was to investigate the relationships between BNP levels measured before and after a standard saline load (SLT), plasma aldosterone (PA), active renin (AR), and LV variables in EH patients without heart failure or valvular disease. Design and method: In 155 EH patients (age 48 ± 12 years, 92 males, 64 treatment-naïve, the remaining 91 after drug wash-out), a SLT (0.9% saline, 2 L in 4 hours) was performed with baseline and post-SLT measurement of PA, AR, BNP pre- and post-test (pre-BNP, post-BNP). Echocardiography with Tissue Doppler Imaging (TDI) was performed, with measurement of indexed LV mass (LVMI), ejection fraction (EF), TDI-S velocity, E/A and E/e’ ratios, and TDI-e’ velocity. Results: Pre-BNP level was higher in females than males, and in patients with previous antihypertensive treatment than in naive patients. Pre-BNP level was significantly and directly related to age, LVMI, E/e’, and inversely related to glomerular filtration (GFR), AR, TDI-S, E/A, and TDI-e’. Post-BNP levels was higher in females and in previously treated patients, and it was positively related to age, E/e’ ratio, and inversely related to GFR, AR, TDI-S, E/A, and TDI-e’. At multivariate analysis pre-BNP level was independently associated with age, female gender, GFR, and AR, while post-BNP level was independently associated with age, AR, and previous antihypertensive treatment. Conclusions: In EH patients, plasma BNP is related with LVMI and LV systolic and diastolic function before and after a SLT, but this relationship seems to be limited to female sex and older subjects. Measurement of BNP might be useful for identification and follow-up of subclinical LV abnormalities in these patients.