Measures Of Ventricular Function Research Articles

Assessment of echocardiographic parameters in children with permanent ventricular pacing

BackgroundEchocardiography is important in the follow-up of children with permanent pacemakers due to the risk for cardiomyopathy. However, the value of standard measurements is unclear in the setting of expected dyssynchrony caused by ventricular pacing. ObjectivesThe study sought to assess and compare echocardiographic parameters of ventricular function in children with chronic ventricular pacing. MethodsEchocardiographic studies of patients with normal cardiac anatomy and ventricular pacing for heart block were retrospectively evaluated for routine measurements of systolic and diastolic ventricular function. ResultsIn 60 echocardiograms that were analyzed, fractional shortening (FS) had moderate correlation with ejection fraction (EF; R = 0.64, p < 0.001) while tissue Doppler (TDI) s waves had poor correlation to EF in the assessment of systolic function. When excluding the two patients with clinical cardiomyopathy, EF and FS had near normal mean z-scores (−0.26 ± 1.68 and 0.07 ± 1.65, respectively). For diastolic function, mean left atrial (LA) area measurements were also normal (mean z-score −0.01 ± 0.9). However, TDI measures and E/A wave ratio had poor correlation and appeared to underestimate diastolic function. ConclusionsFS and EF are moderately correlated to each other and may both be appropriate in the evaluation of systolic function in chronically paced children. TDI values may be misleading, measuring low diastolic function despite normal LA area.

Effect of empagliflozin on myocardial structure and function in patients with type 2 diabetes at high cardiovascular risk: the SIMPLE randomized clinical trial.

To investigate the effects of 13weeks treatment with empagliflozin in patients with high-risk type-2 diabetes mellitus on echocardiographic measures of left ventricular (LV) structure and function compared to placebo. A total of 91 patients were randomized to treatment with empagliflozin (25mg/day, n = 45) or matching placebo (n = 45) for 13weeks. Left ventricular (LV) mass, volumes and geometry as well as measures of LV systolic and diastolic function were measured using echocardiography at baseline and follow up. Mean LV mass index (LVMi) was reduced by -11.5g/m2 (95% CI -56.4; 33.4, p = 0.03) with empagliflozin compared to -1.4g/m2 (95% CI -36.5; 33.8, p = 0.63) for placebo. The proportion of patients with LV hypertrophy was reduced by 16.3% (p = 0.04) in the empagliflozin group compared to 1.1% in the placebo group (p = 1.00). The proportion of patients with left atrial volume index > 34mL/m2 was reduced by 20.0% (p = 0.02) with empagliflozin compared to 9.5% for placebo (p = 0.45) and the E/e' ratio decreased (∆-0.8 (1.9) vs. ∆0.5 (2.0), p < 0.01). 13weeks empagliflozin treatment in patients with type-2 diabetes at high CV risk significantly reduced LV mass, improved LV geometry and improved diastolic function compared to placebo.

Changes in aortic valve hemodynamics and ventricular functional measurements in patients undergoing transcatheter and surgical aortic valve replacement: a head-to-head comparison

Abstract Introduction Both surgical and transcatheter aortic valve replacement are effective interventions for treatment of patients with severe aortic stenosis. Data from landmark randomized trials have shown comparable improvement in aortic valve hemodynamics and left ventricular remodeling. Whether similar patterns will be observed in real-world practice has not been completely investigated. Purpose To compare the impact of transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) on short- and intermediate-term changes in aortic valve hemodynamics and left ventricular reverse-remodeling. Methods A total of 213 patients with severe AS were referred for TAVR (n=137) or SAVR (n=76) at a single center (August/ 2015-Feb/ 2021). Patient demographics and echocardiographic parameters of aortic valve stenosis severity were collected retrospectively. Changes over-time in aortic valve area, mean gradient, dimensionless index, left ventricular ejection fraction (EF), and ventricular septal thickness were examined using linear mixed models. Results Patients undergoing TAVR were older with higher STS risk scores and a greater burden of comorbidities (Table). Over a median follow-up of 13 months (IQR 4–31), both groups experienced a significant reduction in aortic valve mean gradient (25.7 mmHg with TAVR and 18.8 mmHg with SAVR), with no significant between-group difference (P=0.15). Aortic valve dimensionless index significantly increased in TAVR and SAVR groups (0.23 and 0.13, respectively) and was more pronounced in the TAVR group (P=0.01). Similarly, aortic valve area increased significantly in both groups (0.66 cm2 and 0.42 cm2, respectively) without a significant across-group difference (P=0.07). On the other hand, left ventricular ejection fraction did not change significantly over time (−0.61 and 1.15 EF points, respectively) with no significant between-group difference at 12 months (P=0.06). Ventricular septal thickness was significantly reduced in both groups, with no significant between group difference (P=0.4; Figure). Conclusion In this real-world experience, both TAVR and SAVR were associated with significant improvement in aortic valve hemodynamic parameters and modest reverse left ventricular remodeling. Furthermore, these changes were comparable with both modalities, adding to available evidence from randomized clinical trials on beneficial effects of both TAVR and SAVR. Funding Acknowledgement Type of funding sources: None. Table 1Figure 1

The role of premorbid transthoracic echocardiogram in identifying adverse clinical outcomes in patients admitted with COVID-19

Abstract Background/Introduction The novel coronavirus disease (COVID-19) inpatient mortality rate is approximately 20% in the United States. Reports have described a wide pattern of abnormalities in echocardiograms performed in patients admitted with COVID-19. The role of premorbid transthoracic echocardiogram (TTE) in the prediction of COVID-19 severity and mortality is yet to be fully assessed. Purpose To assess whether a pre-COVID TTE can identify patients at high risk of adverse outcomes who are admitted with COVID-19. Methods All patients who underwent a TTE from one year to one month prior to an index inpatient admission for COVID-19 were retrospectively enrolled across five clinical sites. Demographic information, medical history, and laboratory data were included for analysis. Echocardiograms were analyzed by an observer blinded to clinical data. Linear and logistic regressions were performed to detect the association of variables with death, invasive mechanical ventilation, initiation of dialysis, and a composite of these endpoints during the COVID-19 admission. Outcomes were then adjusted for a risk score using inverse propensity weighting incorporating age, sex, diabetes, hypertension, obstructive sleep apnea, history of atherosclerotic cardiovascular disease, atrial fibrillation, diuretic use, and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use. Results There were 104 patients (68±15 years old, 49% male, BMI 31.4±9.1kg/m2) who met inclusion criteria (baseline characteristics in Table 1). Mean time from TTE to positive SARS-CoV-2 PCR test was 139±91 days. Twenty-nine (28%) participants died during the index COVID-19 admission. There was no association of pre-COVID echocardiographic measures of systolic ventricular function with any endpoint. Diastolic function, as assessed by LV e', was associated with mortality (Table 2). There were 25 patients (24%) with a normal lateral e' (≥10cm/s); none died. There were 35 (34%) patients with LV e' lateral velocity &amp;lt;8 cm/s, of whom 15 (43%) died. LV e' lateral velocity &amp;lt;8 cm/s was associated with an unadjusted odds ratio of 7.69 (95% confidence interval [CI] 2.26–26.19) for death and 3.25 (95% CI 1.11–9.54) for the composite outcome. The odds ratio for death was 4.76 (95% CI 1.10–20.61) and 3.78 (95% CI 0.98–14.6) for the composite outcome after adjustment for clinical risk factors (Table 2). Conclusion In patients with an echocardiogram prior to COVID-19, impaired diastolic function as represented by an abnormal LV e' lateral velocity was associated with both inpatient COVID-19 mortality and a composite outcome of death, mechanical ventilation, and initiation of dialysis, even after adjustment for multiple co-morbidities and medication use. Knowledge of the pre-COVID TTE results may help clinicians identify patients at higher risk of adverse outcomes during an admission for COVID-19. Funding Acknowledgement Type of funding sources: None.

Assessment of Myocardial Function During Blood Pressure Manipulations Using Feature Tracking Cardiovascular Magnetic Resonance.

Background: Coronary autoregulation is a feedback system, which maintains near-constant myocardial blood flow over a range of mean arterial pressure (MAP). Yet in emergency or peri-operative situations, hypotensive or hypertensive episodes may quickly arise. It is not yet established how rapid blood pressure changes outside of the autoregulation zone (ARZ) impact left (LV) and right ventricular (RV) function. Using cardiovascular magnetic resonance (CMR) imaging, measurements of myocardial tissue oxygenation and ventricular systolic and diastolic function can comprehensively assess the heart throughout a range of changing blood pressures.Design and methods: In 10 anesthetized swine, MAP was varied in steps of 10–15 mmHg from 29 to 196 mmHg using phenylephrine and urapidil inside a 3-Tesla MRI scanner. At each MAP level, oxygenation-sensitive (OS) cine images along with arterial and coronary sinus blood gas samples were obtained and blood flow was measured from a surgically implanted flow probe on the left anterior descending coronary artery. Using CMR feature tracking-software, LV and RV circumferential systolic and diastolic strain parameters were measured from the myocardial oxygenation cines.Results: LV and RV peak strain are compromised both below the lower limit (LV: Δ1.2 ± 0.4%, RV: Δ4.4 ± 1.2%, p < 0.001) and above the upper limit (LV: Δ2.1 ± 0.4, RV: Δ5.4 ± 1.4, p < 0.001) of the ARZ in comparison to a baseline of 70 mmHg. LV strain demonstrates a non-linear relationship with invasive and non-invasive measures of oxygenation. Specifically for the LV at hypotensive levels below the ARZ, systolic dysfunction is related to myocardial deoxygenation (β = −0.216, p = 0.036) in OS-CMR and both systolic and diastolic dysfunction are linked to reduced coronary blood flow (peak strain: β = −0.028, p = 0.047, early diastolic strain rate: β = 0.026, p = 0.002). These relationships were not observed at hypertensive levels.Conclusion: In an animal model, biventricular function is compromised outside the coronary autoregulatory zone. Dysfunction at pressures below the lower limit is likely caused by insufficient blood flow and tissue deoxygenation. Conversely, hypertension-induced systolic and diastolic dysfunction points to high afterload as a cause. These findings from an experimental model are translatable to the clinical peri-operative environment in which myocardial deformation may have the potential to guide blood pressure management, in particular at varying individual autoregulation thresholds.

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

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

Myocardial efficiency in severe asymptomatic primary mitral regurgitation: relation to quantitative measures of regurgitation

Abstract Objectives To study the association of myocardial external efficiency (MEE) in mitral regurgitation (MR) towards routinely used quantitative indicators of disease severity and progression. Background Quantitative assessment of LV function and regurgitation in asymptomatic severe primary MR is crucial for management. MEE is a load-independent indicator of mechano-energetic coupling and can be measured non-invasively using 11C-acetate positron emission tomography (PET). The role of MEE in this setting has not been studied. Methods 48 asymptomatic patients with severe primary mitral regurgitation underwent PET, echo, and CMR on the same day. MEE was automatically derived from PET as the ratio of cardiac work (cardiac output * mean arterial pressure) and total left ventricular (LV) oxygen consumption (mean MVO2 * LV mass). LV function and mitral regurgitant volumes (RegVol) were measured by echo and CMR. MEE in MR was compared to healthy volunteers (n=9). MEE and parameters of regurgitation severity and of LV volumes and function were studied as predictors of outcome (valve surgery or death). Results MEE was reduced in MR (21.5±4.2%) vs healthy volunteers (32.0±5.6%, p&amp;lt;0.001) and showed weak but significant correlations (r2&amp;lt;0.25) with regurgitation severity and LV volumes. There were 23 cardiac events (valve surgery: 22; cardiovascular death: 1) during follow-up (median 2.7 years, IQR 1.9–3.2). Univariate Cox models showed that MEE, echocardiographic left atrial volume as well as RegVol and LV ventricular volumes from both echo and CMR were significant outcome predictors (all p&amp;lt;0.05), while LVEF and NT-pro-BNP were not (p&amp;gt;0.05). Prediction by MEE was not affected by age, sex or BMI. When categorically divided by the median MEE was a strong predictor in Kaplan-Meier analysis (log-rank p=0.0004, figure 1) and remained independently significant, compared to all other univariate predictors in bivariate Cox models. Conclusions This study suggests an important role of energetic insufficiency in progression of asymptomatic severe primary MR. Reduced MEE was linked to outcome independently of standard functional measures of regurgitation severity or left ventricular size and function. Strategies for improvement of myocardial energetics in MR are warranted. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swedish Heart-Lung Foundation Figure 1

Inclusion of echocardiographic measure of right ventricular function in the non-invasive French pulmonary arterial hypertension risk stratification method

Abstract Background Although preserved right ventricular (RV) function is consistently associated with better survival in pulmonary arterial hypertension (PAH), the French risk assessment method has not yet considered echocardiographic criteria of RV function. Purpose In the present study, we tested the value of tricuspid annular plane systolic excursion (TAPSE) measured by echocardiography for non-invasive PAH risk assessment. Methods We retrospectively studied a cohort of 306 incident PAH patients treated in two French expert centers who underwent follow-up TAPSE measurement from echocardiographic apical 4-chamber view in addition to previously validated invasive and non-invasive risk stratification variables. The primary composite outcome was 3-year lung transplantation free survival after follow-up assessment. Results At re-evaluation, 66% of patients were in NYHA functional class I-II and mean pulmonary arterial pressure, cardiac index, N-Terminal pro brain natriuretic peptide (NTproBNP), and 6-minute walk distance (6MWD) were 40±16 mmHg, 3.5±1.1 L/min/m2, 270 [interquartile range (IQR) 896] ng/L and 401 (IQR 213) meters, respectively. The primary outcome occurred in 58 (19%) patients. In multivariable Cox regression analysis, NYHA functional class I-II (p=0.02), NTproBNP &amp;lt;300 ng/L or BNP &amp;lt;50 ng/L (p=0.02), 6MWD &amp;gt;440m (p=0.049) and TAPSE≥17 mm (p=0.02) were associated with lung transplantation free survival. TAPSE provided similar information over 6MWD when both were used alternatively to stratify PAH patients at low risk (log-rank&amp;lt;0.001); Harrell's c-index 0.73. Conclusion Three dichotomized low-risk criteria (TAPSE, 6MWD and NTproBNP or BNP plasma levels) allow non-invasive risk assessment in PAH. Funding Acknowledgement Type of funding sources: None. 3-years transplant-free survival

Myocardial contraction fraction by echocardiography and mortality in cardiac intensive care unit patients

BackgroundThe myocardial contraction fraction (MCF) is proposed as an improved measure of left ventricular (LV) systolic function that overcomes important limitations of the left ventricular ejection fraction (LVEF). We sought to determine whether a low MCF was associated with higher mortality in cardiac intensive care unit (CICU) patients. MethodsWe retrospectively analyzed unique Mayo Clinic CICU patients from 2007 to 2018 with MCF calculated as the ratio of the stroke volume to the left ventricular myocardial volume from a transthoracic echocardiogram within 1 day of CICU admission. Multivariable logistic regression analyzed the association between MCF and hospital mortality, after adjustment for LVEF and clinical variables. ResultsWe included 4794 patients with a mean age of 68.0 ± 14.8 years (37.1% females). The mean MCF was 0.41 ± 0.16, and was lower in the 6.6% of patients who died in the hospital (0.32 ± 0.14 versus 0.42 ± 0.16, p < 0.001). On multivariable analysis, higher MCF remained associated with lower hospital mortality (adjusted OR 0.78 per 0.1 higher, 95% CI 0.69–0.89, p < 0.001), whereas LVEF was not significantly associated with hospital mortality (unadjusted OR 0.91 per 10% higher, OR 95% CI 0.82–1.02, p = 0.09). Patients with MCF <0.2 had the highest in-hospital mortality, and those with MCF ≥0.5 had the lowest in-hospital mortality, irrespective of admission diagnosis or LVEF. ConclusionsMCF demonstrated a strong, inverse relationship with hospital mortality in CICU patients, even after adjusting for LVEF and clinical variables. MCF can be used to identify prognostically-relevant myocardial dysfunction at the bedside, even among patients with preserved LVEF.

Associations of the Dietary Approaches to Stop Hypertension dietary pattern with cardiac structure and function

Background and aimsVarious food groups have been associated with measures of left ventricular geometry and function. Whether the Dietary Approaches to Stop Hypertension (DASH) dietary pattern in mid-life is associated with a favorable cardiac structure and function later in life is unknown. Methods and resultsThe study population consisted of the Atherosclerosis Risk in Communities study participants free of cardiovascular disease at study visit 3 in 1993–1995. Dietary intake was assessed by food frequency questionnaire at study visits 1 (1987–1989) and 3 (1993–1995). Participants who underwent transthoracic echocardiograms at the Jackson field center at visit 3 (n = 1974) and at all field centers at study visit 5 (2011–2013; n = 4651) were included in this study. General linear regression was used to evaluate associations between dietary intake and markers of cardiac structure and function adjusting for potential confounders. Higher DASH score was associated with lower left ventricle mean wall thickness and higher absolute value of longitudinal strain at visit 5 (ptrend = 0.004 and < 0.001, respectively). ConclusionThe DASH dietary pattern in midlife was favorably associated with left ventricle structure and systolic function later in life. These results emphasize the importance of adhering to a healthy eating plan as one lifestyle measure to preserve cardiac structure and function.

Citrate-Saline-Formulated mRNA Delivery into the Heart Muscle with an Electromechanical Mapping and Injection Catheter Does Not Lead to Therapeutic Effects in a Porcine Chronic Myocardial Ischemia Model

Based on recent success in using modified RNA in clinical applications, we tested the safety, feasibility, and efficacy of direct delivery of citrate-saline-formulated mRNA into an hibernating ischemic heart muscle using an electromechanical mapping and injection catheter system (NOGA/Myostar) in a porcine chronic myocardial ischemia model. Chronic ischemia was induced in domestic pigs (n = 24) using a bottleneck stent placed in the left anterior descending coronary artery. Low (1 mg) and high (7.5 mg) doses of citrate-saline-formulated vascular endothelial growth factor (VEGF)-A165 mRNA were administered in the study. LacZ mRNA and citrate-saline buffer were used as controls. Ten intramyocardial injections (200 μL each) of the mRNAs or citrate-saline buffer were given endovascularly into the hibernating ischemic myocardium using the NOGA catheter. Positron emission tomography 15O-radiowater imaging was performed 7 days after the induction of ischemia and 28 days after the mRNA delivery to measure quantitative myocardial blood perfusion. Coronary angiography, left ventricular function measurements, and clinical chemistry were obtained at each time point. Thirty-five days after the mRNA transfers, pigs were sacrificed, and infarct size and general histology were analyzed. LacZ mRNA pigs were sacrificed 24 h after the transduction. Citrate-saline-formulated mRNA delivery into the ischemic myocardium with endovascular injection catheter did not lead to meaningful transduction with the translation of VEGF-A165, nor therapeutic effects in the heart. VEGF-A165 mRNA showed no statistically significant improvements in left ventricular ejection fraction (LVEF), cardiac output, myocardial perfusion, infarct size, collateral growth, or capillary area in the study groups. However, there was a trend in the high-dose group toward an improved LVEF and cardiac output at rest. No significant adverse effects were observed. In conclusion, the NOGA/Myostar injection catheter system is ineffective in delivering citrate-saline-formulated mRNAs into the heart muscle with the doses and methods used in a porcine chronic myocardial ischemia model.

Right ventricular function as assessed by cardiac magnetic resonance imaging-derived strain parameters compared to high-fidelity micromanometer catheter measurements.

Right ventricular function has prognostic significance in patients with pulmonary hypertension. We evaluated whether cardiac magnetic resonance-derived strain and strain rate parameters could reliably reflect right ventricular systolic and diastolic function in precapillary pulmonary hypertension. End-systolic elastance and the time constant of right ventricular relaxation tau, both derived from invasive high-fidelity micromanometer catheter measurements, were used as gold standards for assessing systolic and diastolic right ventricular function, respectively. Nineteen consecutive precapillary pulmonary hypertension patients underwent cardiac magnetic resonance and right heart catheterization prospectively. Cardiac magnetic resonance data were compared with those of 19 control subjects. In pulmonary hypertension patients, associations between strain- and strain rate-related parameters and invasive hemodynamic parameters were evaluated. Longitudinal peak systolic strain, strain rate, and early diastolic strain rate were lower in PAH patients than in controls; peak atrial-diastolic strain rate was higher in pulmonary hypertension patients. Similarly, circumferential peak systolic strain rate was lower and peak atrial-diastolic strain rate was higher in pulmonary hypertension. In pulmonary hypertension, no correlations existed between cardiac magnetic resonance-derived and hemodynamically derived measures of systolic right ventricular function. Regarding diastolic parameters, tau was significantly correlated with peak longitudinal atrial-diastolic strain rate (r = −0.61), deceleration time (r = 0.75), longitudinal systolic to diastolic time ratio (r = 0.59), early diastolic strain rate (r = −0.5), circumferential peak atrial-diastolic strain rate (r = −0.52), and deceleration time (r = 0.62). Strain analysis of the right ventricular diastolic phase is a reliable non-invasive method for detecting right ventricular diastolic dysfunction in PAH.

Multi-View 3-D Fusion Echocardiography: Enhancing Clinical Feasibility with a Novel Processing Technique

A novel system for fusing 3-D echocardiography data sets from complementary acoustic windows was evaluated in 12 healthy volunteers and 12 patients with heart failure. We hypothesized that 3-D fusion would enable 3-D echocardiography in patients with limited acoustic windows. At least nine 3-D data sets were recorded, while three infrared cameras tracked the position and orientation of the transducer and chest respiratory movements. Corresponding 2-D planes of the fused 3-D data sets and of single-view 3-D data sets were assessed for image quality and compared with measurements of left ventricular function obtained with contrast 2-D echocardiography. The signal-to-noise ratio in accurately fused 3-D echocardiography recordings improved by 55% in systole (p < 0.001) and 47% in diastole (p < 0.00001) compared with the apical single-view recordings. The 3-D data sets acquired during short breath holds were successfully fused in 11 of 12 patients. The improvement in endocardial border definition (from 11.7 ± 6.0 to 24.0 ± 3.3, p < 0.01) enabled quantitative assessment of left ventricular function in 10 patients, with no significant difference in ejection fraction compared with contrast 2-D echocardiography. In patients with heart failure and limited acoustic windows, the novel fusion protocol provides 3-D data sets suitable for quantitative analysis of left ventricular function.

Exercise Training Induces Left- but not Right-sided Cardiac Remodelling in Olympic Rowers.

Whilst the athlete's heart has been extensively described, less work has focused on the potential for elite athletes to demonstrate further cardiac remodelling upon an increase in training volume. Moreover, little work explored potential side-specific cardiac remodelling. Therefore, we examined the impact of an increase in training volume across 9-months in elite rowers on left- and right-sided cardiac structure, function and mechanics (i. e. longitudinal, radial and circumferential strain, twist and strain-volume loops). As part of the preparations to the 2012 Olympic Games, twenty-seven elite rowers (26.4±3.7years, 19 male) underwent echocardiography prior to and post (9 months) an increase in training volume (24 to 30-35 h weekly). Training increased left ventricular structure, including wall thickness, diameter, volume, mass and LV twist (all p<0.05). Female rowers demonstrated larger adaptation in left ventricular diameter and mass compared to male rowers (both p<0.05). No changes were observed in other measures of left ventricular function in both sexes (all p>0.05). The 9-month intervention showed no change in right ventricular/atrial structure, function or mechanics (all p>0.05). In conclusion, our data revealed that 9-month increased training volume in elite rowers induced left-sided (but not right-sided) structural remodelling, concomitant with an increase in left ventricular twist, with some changes larger in women.

Identifying Risk Factors for Complicated Post-operative Course in Tetralogy of Fallot Using a Machine Learning Approach.

Introduction: Tetralogy of Fallot (TOF) repair is associated with excellent operative survival. However, a subset of patients experiences post-operative complications, which can significantly alter the early and late post-operative course. We utilized a machine learning approach to identify risk factors for post-operative complications after TOF repair.Methods: We conducted a single-center prospective cohort study of children <2 years of age with TOF undergoing surgical repair. The outcome was occurrence of post-operative cardiac complications, measured between TOF repair and hospital discharge or death. Predictors included patient, operative, and echocardiographic variables, including pre-operative right ventricular strain and fractional area change as measures of right ventricular function. Gradient-boosted quantile regression models (GBM) determined predictors of post-operative complications. Cross-validated GBMs were implemented with and without a filtering stage non-parametric regression model to select a subset of clinically meaningful predictors. Sensitivity analysis with gradient-boosted Poisson regression models was used to examine if the same predictors were identified in the subset of patients with at least one complication.Results: Of the 162 subjects enrolled between March 2012 and May 2018, 43 (26.5%) had at least one post-operative cardiac complication. The most frequent complications were arrhythmia requiring treatment (N = 22, 13.6%), cardiac catheterization (N = 17, 10.5%), and extracorporeal membrane oxygenation (ECMO) (N = 11, 6.8%). Fifty-six variables were used in the machine learning analysis, of which there were 21 predictors that were already identified from the first-stage regression. Duration of cardiopulmonary bypass (CPB) was the highest ranked predictor in all models. Other predictors included gestational age, pre-operative right ventricular (RV) global longitudinal strain, pulmonary valve Z-score, and immediate post-operative arterial oxygen level. Sensitivity analysis identified similar predictors, confirming the robustness of these findings across models.Conclusions: Cardiac complications after TOF repair are prevalent in a quarter of patients. A prolonged surgery remains an important predictor of post-operative complications; however, other perioperative factors are likewise important, including pre-operative right ventricular remodeling. This study identifies potential opportunities to optimize the surgical repair for TOF to diminish post-operative complications and secure improved clinical outcomes. Efforts toward optimizing pre-operative ventricular remodeling might mitigate post-operative complications and help reduce future morbidity.

Two-Dimensional Echocardiographic Right Ventricular Size and Systolic Function Measurements Stratified by Sex, Age, and Ethnicity: Results of the World Alliance of Societies of Echocardiography Study

Echocardiographic assessment of right ventricular (RV) systolic function is an important component of clinical decision making. Although professional societies have worked to define normal ranges of RV size and function, their guidelines have not included the impacts of age, sex, and ethnicity on these parameters, as they have for the left ventricle. The World Alliance of Societies of Echocardiography study was designed to investigate the effects of age, sex, and ethnicity on all cardiac chambers. The aim of this study was to explore whether these differences exist for RV systolic parameters. Adequate two-dimensional RV-focused views for the measurement of systolic parameters, including fractional area change and global and free wall longitudinal strain, were available in 1,913 subjects (mean age, 47±17years; 51% men). Basal and mid-RV dimensions, length, tricuspid annular peak systolic excursion, tissue Doppler S' velocity, and myocardial performance index were also measured. Subjects were grouped by age (<40, 41-65, and >65years), with results also stratified by sex and ethnicity (Asian, black, or white) and analyzed using vendor-independent software. Differences among groups were evaluated using analysis of variance. Women had smaller absolute and indexed RV areas and absolute RV dimensions and higher magnitudes of fractional area change, free wall strain, and global longitudinal strain compared to men. With respect to age, most of the statistically significant differences were noted between the <40- and >65-year age groups, with RV areas and lengths smaller in older age groups and RV functional parameters (S', fractional area change, tricuspid annular plane systolic excursion, global longitudinal strain, free wall strain, and myocardial performance index) showing minimal decreases or no changes with age. Although there were no meaningful differences in functional parameters among ethnic groups, RV size was smallest in Asians. These findings suggest that although two-dimensional RV parameters are age and sex dependent, association with race is less apparent, excepting that the Asian population appears to have smaller chamber sizes compared with whites and blacks.

Effect of cardiosphere-derived cells on segmental myocardial function after myocardial infarction: ALLSTAR randomised clinical trial

BackgroundMost cell therapy trials failed to show an improvement in global left ventricular (LV) function measures after myocardial infarction (MI). Myocardial segments are heterogeneously impacted by MI. Global LV function...

Gene therapy knockdown of Hippo signaling induces cardiomyocyte renewal in pigs after myocardial infarction.

Human heart failure, a leading cause of death worldwide, is a prominent example of a chronic disease that may result from poor cell renewal. The Hippo signaling pathway is an inhibitory kinase cascade that represses adult heart muscle cell (cardiomyocyte) proliferation and renewal after myocardial infarction in genetically modified mice. Here, we investigated an adeno-associated virus 9 (AAV9)-based gene therapy to locally knock down the Hippo pathway gene Salvador (Sav) in border zone cardiomyocytes in a pig model of ischemia/reperfusion-induced myocardial infarction. Two weeks after myocardial infarction, when pigs had left ventricular systolic dysfunction, we administered AAV9-Sav-short hairpin RNA (shRNA) or a control AAV9 viral vector carrying green fluorescent protein (GFP) directly into border zone cardiomyocytes via catheter-mediated subendocardial injection. Three months after injection, pig hearts treated with a high dose of AAV9-Sav-shRNA exhibited a 14.3% improvement in ejection fraction (a measure of left ventricular systolic function), evidence of cardiomyocyte division, and reduced scar sizes compared to pigs receiving AAV9-GFP. AAV9-Sav-shRNA-treated pig hearts also displayed increased capillary density and reduced cardiomyocyte ploidy. AAV9-Sav-shRNA gene therapy was well tolerated and did not induce mortality. In addition, liver and lung pathology revealed no tumor formation. Local delivery of AAV9-Sav-shRNA gene therapy to border zone cardiomyocytes in pig hearts after myocardial infarction resulted in tissue renewal and improved function and may have utility in treating heart failure.

Associations between menopause, cardiac remodeling, and diastolic function: the CARDIA study.

Heart failure with preserved ejection fraction (HFpEF) affects more women than men. Menopause may influence HFpEF development in women. We assessed cross-sectional and longitudinal associations between menopause and echocardiographic measures of left ventricular (LV) function and cardiac remodeling. We studied 1,723 women with available echo data from at least two of: year 5 (Y5) (1990-1991), Y25 (2010-2011), or Y30 (2015-2016) in the Coronary Artery Risk Development in Young Adults study. Cardiac structure and function were measured using 2D and Doppler echocardiography. Cross-sectional associations between menopausal status and repeated echo measures at Y25 and Y30 were analyzed using linear mixed models. Two-segmented models were used to compare longitudinal changes in echocardiographic measures in the premenopausal period to changes in the postmenopausal period. Mean ± SD age (years) at enrollment was 27 ± 3 in those with menopause by Y25, 25 ± 3 in those with menopause between Y25 and Y30, and 21 ± 3 in those premenopausal at Y30. There were no significant differences in race, body mass index, systolic blood pressure, or diabetes between the groups. Postmenopausal women had higher early diastolic mitral inflow (E) to annular (e') velocity ratio than premenopausal after adjusting for demographics and risk factors (P < 0.05). Menopause was associated with relative increases in the rates of change in LV mass and left atrial volume, even after adjustment. Change in E/e' ratio was similar before and after menopause. Menopause is associated cross-sectionally with worse diastolic function and longitudinally with adverse LV and left atrial remodeling. This may contribute to the increased HFpEF risk in postmenopausal women.

Effects of cardiac medications on ventricular function in patients with Duchenne muscular dystrophy–related cardiomyopathy

The DMD Care Considerations Working Group Guidelines 2010 recommended treating cardiac dystrophinopathy with angiotensin-converting enzyme-inhibitor (ACEi) and beta-blocker (BB) therapy to prevent the progressive decline in left ventricular function expected from earlier, natural history studies. The aim of this research was to audit change in measures of left ventricular function over 8 years to 4 years before and 4 years after deploying an ACEi/BB combination systematically at a dedicated "cardiology-muscle" clinic. This is an institutionally registered, retrospective, case-file-based audit of serial echocardiographic measures of left ventricular fractional shortening accumulated over the period 1995 to 2015. Data from 104 genetically confirmed Duchenne muscular dystrophy (DMD) patients, aged 22.2 ± 5.3 years at data censure, were included. Mean age at first detection of left ventricular dysfunction was 15.1± 4.2 years, but older in those on maintenance steroid therapy (16.8± 4.2 vs 14.5± 4.1 years; P= .04). Group mean fractional shortening fell by 1.5%/year over the 4 years before therapy, but this decreased to 0.9%/year over the first 4 years after starting therapy. Analysis of limited left ventricular ejection fraction measures showed similar but nonsignificant changes. Neither age at detection of left ventricular dysfunction nor fractional shortening percent at time of therapy initiation affected the beneficial response. The results support the international DMD recommendations of the time. This combination of cardiac medications helps stabilize heart function. For the best long-term effects, therapy needs to be initiated no later than on first detection left ventricular impairment.