Myocardial Shortening Research Articles

Evaluation of Right and Left Ventricular Deformation Analysis in İdiopathic Right Bundle Branch Block by Speckle Tracking Echocardiography.

Idiopathic right bundle branch block (RBBB) is often seen as harmless and common. However, many studies show it might be linked to negative health outcomes. So, it is crucial to fully understand how RBBB affects the heart's ventricles. This study aims to examine the right and left ventricular systolic functions in patients with idiopathic RBBB and compare them to those in a healthy control group. Echocardiographic images were obtained from patients with idiopathic RBBB and healthy control participants. Conventional echocardiographic parameters were measured. Two-dimensional (2D) speckle tracking strain analysis was used to assess deformation indices. Thirty-nine patients with idiopathic RBBB and 35 healthy participants were included in the study. There were no significant differences in the chamber dimensions of the left ventricle (LV) and right ventricle (RV) between the groups. LV ejection fraction (EF), RV fractional area change (FAC), and tricuspid annular plane systolic excursion (TAPSE) measurements were similar between the groups. LV global longitudinal strain (GLS) (-25.5±5.7% vs. -22.1±4.2%, p<0.05), RV GLS (-26.9±4.6% vs. -24.0±4.4%, p<0.05), and interventricular septum longitudinal strain (IVS LS) (-24.3±4.9% vs. -19.1±4.2%, p<0.05) were significantly reduced in patients with idiopathic RBBB compared to controls, indicating impaired myocardial shortening. Significant differences were also observed in LV (15 [5-30] vs. 30 [20-60], p<0.05) and RV (18 [7-35] vs. 36 [24-80], p<0.05) mechanical dispersion, with the differences being more pronounced for the RV between the groups. LV torsion (2.1±0.6 vs. 1.6±0.5, p<0.05) was also worse in patients with idiopathic RBBB. Our findings show that idiopathic RBBB significantly affects the longitudinal strain and synchronization of both the LV and RV.

Cardiovascular problems in rabbits in reference to hypothyroidism - a four-year retrospective study.

The effects of T4 are mainly manifested by positive ino- and chronotropism. The syndrome accompanying hypothyroidism in rabbits (impaired myocardial contractility and reduced ejection capacity) is caused by a deficiency of thyroid hormones - especially T4. The study group consisted of a total of 41 animals: 15 males and 26 females, ranging in age from 2 months to 8 years, with echocardiogram showing reduced fractional shortening (<30%), with normal results of heamatological and biochemical tests. Blood was collected in order to measure T4 level. Echocardiographic examinations were performed with two-dimensional (2D) imaging, M-mode measurements and the pulsed/colour-labelled Doppler technique. Statistical analysis was performed using Statistica 13.0. Correlations were determined: between serum thyroxine concentration and the value of the fraction of shortening in the groups: young animals (up to 5 years of age) and older animals, females and males, and sterilised and non-sterilised animals. Statistical analysis showed a positive correlation between T4 levels in the blood of the test animals and myocardial fractional shortening and heart rate and left-atrial to aortic ratio (LA/Ao) in the pre-treatment period. A positive correlation was also shown after dividing the patients into 2 groups based on their age (below 5 years vs. 5 years and over), sex (male and female rabbits) and fact of sterilization (yes/no). Our study unequivocally confirmed a positive correlation between the decreased serum T4 concentration and reduced fractional shortening, indicating decreased cardiac systolic function in hypothyroid rabbits.

Retrospective study of left and right ventricular strain mechanics among neonates undergoing therapeutic hypothermia for neonatal encephalopathy

PurposeEarly diagnosis of impaired myocardial function and timely therapeutic hypothermia is vital among patients with Neonatal Encephalopathy (NE). Traditional markers of myocardial function (Left Ventricular Ejection Fraction (LV EF) & LV Fractional Shortening (LV FS) can be variably reduced. Speckle tracking echocardiography (STE) is a more sensitive marker for impairment but remains inadequately studied in this patient population. MethodsA retrospective study of neonates who underwent therapeutic hypothermia (TH) for NE from 2009 to2020 were matched 1:1 with normal neonates with normal echocardiograms performed for indications other than NE. Matching was based on gestational age, birth weight, days of age, and sex. Left ventricular 4 Chamber (4Ch) strain, right ventricular 4 Chamber (RV 4Ch), and RV free wall strain (RV FWS) were measured offline using vendor independent strain software (TomTec, GMBH, Munich, Germany). ResultsNinety pairs of NE patients and controls were studied. Compared to controls, RV 4Ch strain (−17.3 % vs. -19.6 %), RV FWS (−18.8 % vs. -21.9 %), and RV fractional area change (FAC) (35 % vs. 37 %) were lower in NE cases (all p < 0.001), while differences in LV 4Ch strain, LV EF, and LV FS did not reach statistical significance. Moderate/severe NE (72 %) was associated with lower LV 4Ch strain compared to mild NE (−22.2 %/−19.3 % vs. -25.4 %, p = 0.004). RV 4Ch strain (−14.9 % vs. -18.8 %, p = 0.020) and RV FAC (27 % vs. 36 %, p = 0.006) were lower in severe NE compared to mild NE. Lower LV 4Ch was associated with need for chest compressions (−18.5 % vs. -23.3 %), epinephrine at delivery (−19.3 % vs. -23.4 %), and decreased survival to discharge (−15.9 % vs. -22.7 %). ConclusionsRV and LV strain mechanics are impaired in NE patients. Lower RV Strain and LV 4Ch strain were associated with need for increased medical support and decreased survival to discharge.

Left ventricular myocardial work predicts clinical course in patients with heart failure with mildly reduced ejection fraction

Abstract Heart failure with mildly reduced ejection fraction (HFmrEF) often represents a movable patients subset that changes its HF category by increasing or reducing EF. Course prediction is challenging due to insufficient evidence to date. We studied multiple newly established parameters in order to find predictors of clinical course of HFmrEF. Methods 135 patients (61 women) 62±5 years with HFmrEF NYHA II-III on GDMT were enrolled. Longitudinal (GLS), circumferential (GCS) and radial strain (GRS), peak LV twist (LVTR) were measured by speckle tracking from apical and short axis views. Left ventricular (LV) global myocardial work (GW) index (GWI) was obtained from pressure-strain loops derived from LV GLS and supine systemic blood pressure measured right before the image acquisition. Then constructive GW (GCW) as the sum of positive work due to myocardial shortening during systole and negative work due to lengthening during isovolumic relaxation, wasted GW (GWW) as energy loss by myocardial lengthening in systole and shortening in isovolumic relaxation and GW efficiency (GWE) as the percentage ratio of constructive work to the sum of constructive work and wasted work were obtained by dedicated software. All parameters were analyzed offline by one experienced specialist. Patients were followed up for 1 year. Results 38 (28%) patients improved EF to the value ≥50%, 31 (23%) reduced EF to ≤40%. Patients with improved EF had significantly higher absolute values of GLS (17.3±2.2 vs 15.8±3.1%, p&amp;lt;0.03), GCS (18.9±2.6 vs 16.1±1.9%, p&amp;lt;0.02), GRS (42.5±7.2% vs 31.3±4.7%, p&amp;lt;0.02), LVT (6.2±2.5° vs 5.3±2.3°, p&amp;lt;0.03), GCW (2253±121 vs 1872±132 mmHg%, p&amp;lt;0.001) and lower GWW (108±7 vs 128±12 mmHg%) compared with patients with later reduced EF. Multivariate analysis showed that lower GCW was associated with EF reduction (HR 0.982, 95% CI 0.969–0.996, p = 0.012). GCW was the powerful predictor of CV events (AUC 0.94) with cut off value of 1495 mmHg% that had 98% sensitivity and 86% specificity. Conclusion LV GCW predicts EF changes in patients with HFmrEF.

Myocardial Strain Imaging: Theory, Current Practice, and the Future.

Myocardial strain imaging by echocardiography or cardiac magnetic resonance (CMR) is a powerful method to diagnose cardiac disease. Strain imaging provides measures of myocardial shortening, thickening, and lengthening and can be applied to any cardiac chamber. Left ventricular (LV) global longitudinal strain by speckle-tracking echocardiography is the most widely used clinical strain parameter. Several CMR-based modalities are available and are ready to be implemented clinically. Clinical applications of strain include global longitudinal strain as a more sensitive method than ejection fraction for diagnosing mild systolic dysfunction. This applies to patients suspected of having heart failure with normal LV ejection fraction, to early systolic dysfunction in valvular disease, and when monitoring myocardial function during cancer chemotherapy. Segmental LV strain maps provide diagnostic clues in specific cardiomyopathies, when evaluating LV dyssynchrony and ischemic dysfunction. Strain imaging is a promising modality to quantify right ventricular function. Left atrial strain may be used to evaluate LV diastolic function and filling pressure.

Myocardial work across different etiologies of right ventricular dysfunction and healthy controls.

Evaluating right ventricular (RV) function remains a challenge. Recently, novel echocardiographic assessment of RV myocardial work (RVMW) by non-invasive pressure-strain loops was proposed. This enables evaluation of right ventriculoarterial coupling and quantifies RV dyssynchrony and post-systolic shortening. We aimed to assess RVMW in patients with different etiologies of RV dysfunction and healthy controls. We investigated healthy controls (n=17), patients with severe functional tricuspid regurgitation (FTR; n=22), and patients with precapillary pulmonary hypertension (PCPH; n=20). Echocardiography and right heart catheterization were performed to assess 1) RV global constructive work (RVGCW; work needed for systolic myocardial shortening and isovolumic relaxation), 2) RV global wasted work (RVGWW; myocardial shortening following pulmonic valve closure), and 3) RV global work efficiency (RVGWE; describes the relation between RV constructive and wasted work). RVGCW correlated with invasive RV stroke work index (r=0.66, P<0.001) and increased in tandem with higher afterload, i.e., was low in healthy controls (454±73 mmHg%), moderate in patients with FTR (687±203 mmHg%), and highest among patients with PCPH (881±255 mmHg%). RVGWE was lower and RVGWW was higher in patients with FTR (86±8% and 91 mmHg% [53-140]) or PCPH (86±10% and 110 mmHg% [66-159]) as compared with healthy controls (96±3% and 10 mmHg%). RVMW by echocardiography provides a promising index of RV function to discriminate between patients with RV volume or pressure overload. The prognostic value of this measure needs to be settled in future studies.

Right ventricular myocardial work by echocardiography: non-invasive assessment of right ventricle function in patients with pulmonary hypertension

Abstract Background Right ventricular myocardial work (RVMW) assessed by transthoracic echocardiography allows to study and analyze the right ventricular (RV) function non-invasively, using RV pressure-strain loops. The association between these novel indexes of RVMW and invasive hemodynamic parameters has not yet been extensively studied, namely in precapillary pulmonary hypertension (PH) population. In right heart catheterization, stroke volume directly reflects right ventricular function in response to its load, and has prognostic implication in PH. Objectives To evaluate the relationship between RVMW and stroke volume index (SVi) measured invasively by right heart catheterization (RHC), in a cohort of patients with group I and group IV PH. Methods A prospective registry of pre-capillary PH patients evaluated in a single tertiary center was used. Echocardiography and RHC were performed in the same day. Dedicated software for left ventricle myocardial work was used for the RV. RV global myocardial work index (RVGWI) was calculated as the area of the RV pressure-strain loops. From RVGWI, RV global constructive work (RVGCW; work contributing to myocardial shortening during systole and lengthening during isovolumic relaxation), RV global wasted work (RVGWW; work contributing to myocardial lengthening during systole and shortening during isovolumic relaxation), and RV global work efficiency (RVGWE; relation between RVGCW and RVGWW) were estimated. Pearson’s correlation was applied to assess correlations between continuous variables. Results 17 pts (80% women, mean age 67 ± 10 years) were included. The average of mean pulmonary arterial pressure (mPAP) was 33 mmHg (± 9,5), of pulmonary vascular resistance (PVR) was 5,7 WU (± 5,1) and of SVi was 40,7 ml/m2 (± 10,8). Conventional echocardiographic parameters for the evaluation of RV systolic function, such as TAPSE, annular tricuspid s’ velocity and fractional area change (FAC), did not correlate with SVi. Moreover, right ventricle-pulmonary artery (RV-PA) coupling and RV GLS also did not correlate with this invasive parameter of right ventricle function. Of the RVMW indexes, RVGWW and RVGWE strongly correlated with SVi: as this invasive parameter decreases, RVGWW (r = -0,560, p = 0,019) increases significantly, whereas RVGWE (r= 0,539, p = 0,026) declines (Fig 1). In our population, RVGWI and RVGCW didn’t correlate significantly with SVi. Conclusions Finding non-invasive methods to evaluate RV function is essential in patients with RV hemodynamic overload, since conventional echocardiographic parameters do not perform well, and RV function is central in prognosis assessment in this population. Novel echocardiographic assessment of RVMW seems to provide a promising index of RV function in PH patients, as demonstrated with its correlation with SVi.Figure 1:Correlation of RVMW with SVi.

Abstract 13419: Transient Coronary Artery to Left Ventricular Fistula With Diastolic Mitral Regurgitation

Introduction: A fistula from a coronary artery to the cardiac chamber is incidentally found in 0.08% to 0.3% of patients undergoing coronary angiography. Case Presentation: A 73-year-old woman with hypertension, diabetes mellitus, chronic renal failure, and nephrosis visited our department due to dyspnea. The patient’s physical examination revealed a blood pressure of 191/109 mmHg and a pulse rate of 77 beats per min. The blood sampling results revealed a plasma brain natriuretic peptide level of 2,001 pg/mL. A 12-lead electrocardiogram showed poor R wave progression in leads V1 to V4. Chest radiography revealed left pleural effusion. Parasternal transthoracic echocardiography showed left ventricular hypertrophy. Left ventricular (LV) ejection fraction was 41%. A pulsed-wave Doppler echocardiography at the mitral inflow showed diastolic mitral regurgitation and a fusion of E and A waves. An unusual myocardial flow was noted in the apical myocardium. It was directed toward the apical surface during systole (Fig. 1a), and directed toward the LV lumen during diastole (Fig. 1b), suggesting coronary artery to LV fistula through sinusoid. Global strain obtained from apical long axis imaging showed myocardial shortening continued to diastole, suggesting post-systolic shortening (PSS). After treatment for hypertension, both of myocardial flow and diastolic MR disappeared. A longitudinal global strain imaging revealed disappearance of PSS. Conclusion: This is a rare case of diastolic MR due to PSS at the fistula from the coronary artery to the left ventricle.

Myocardial Function in Fetuses with Congenital Cytomegalovirus Infection

Introduction: The objective of this study was to investigate myocardial deformation of left (LV) and right ventricle (RV) using 2-dimensional speckle-tracking echocardiography (2D-STE) in fetuses with and without congenital cytomegalovirus (CMV) infection. Methods: This was a prospective single-center study. Vertical transmission was defined by a positive CMV polymerase chain reaction (PCR) test on the amniotic fluid or on the neonate’s urine. Fetuses were divided into group 1 and group 2 if CMV-PCR was positive or negative, respectively. LV and RV global longitudinal strain (GLS) values were obtained and adjusted for gestational age by calculating Z-scores. Univariate analysis was carried out to compare cardiac indices between group 1 and group 2. Results: Fetuses from group 1 (n = 11) had a significantly lower LV myocardial shortening than those from group 2 (n = 32). GLS was −20.7 ± 5.2% and −26.3 ± 4.1%, respectively (p = 0.001). Similarly, GLS Z-score was lower (0.02 ± 0.72) in group 1 than in group 2 (−0.80 ± 0.59) (p = 0.001). Similarly, RV GLS Z-score was significantly impaired in group 1 compared to group 2 (−0.44 ± 1.03 vs. −1.04 ± 0.71, p = 0.041). Conclusion: Fetuses with congenital CMV showed subclinical biventricular myocardial dysfunction. Further studies are needed to confirm the potential role of 2D-STE in identifying fetuses with congenital CMV at risk of postnatal cardiovascular morbidities.

Right ventricular myocardial work characterization in patients with pulmonary hypertension and association with pulmonary hypertension severity

Abstract Funding Acknowledgements Type of funding sources: None. Background Right ventricular myocardial work (RVMW) assessed by transthoracic echocardiography allows to study and analyze the right ventricular (RV) function non-invasively, using RV pressure-strain loops. The association between these novel indexes of RVMW and invasive hemodynamic parameters has not yet been extensively studied, namely in precapillary pulmonary hypertension (PH) population. Objectives To evaluate the relationship between RVMW and the severity of PH through invasive indices of right heart catheterization (RHC) in a cohort of patients with group I and group IV PH. Methods A prospective registry of pre-capillary PH patients evaluated in a single tertiary center was used. Echocardiography and right heart catheterization were performed in the same day. Dedicated software for left ventricle myocardial work was used for the RV. RV global myocardial work index (RVGWI) was calculated as the area of the RV pressure-strain loops. From RVGWI, RV global constructive work (RVGCW; work contributing to myocardial shortening during systole and lengthening during isovolumic relaxation), RV global wasted work (RVGWW; work contributing to myocardial lengthening during systole and shortening during isovolumic relaxation), and RV global work efficiency (RVGWE; relation between RVGCW and RVGWW) were estimated. Pearson’s correlation was applied to assess correlations between continuous variables. Results 17 pts (80% women, mean age 67 ± 10 years) were included. Conventional echocardiographic parameters for the evaluation of RV systolic function, such as TAPSE, annular tricuspid s’ velocity and fractional area change (FAC), did not correlate with mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR). Strong correlations were found between right ventricle-pulmonary artery (RV-PA) coupling and mPAP (r = -0,655, p = 0,006) and RVP(r = - 0,610, p = 0,017), as well as with RV GLS (r = 0,749, p = 0,001 and r = 0,622, p = 0,01, respectively). Of the RVMW indexes, RVGWI, RVGWW and RVGWE strongly correlated with mPAP and PVR: as these invasive parameters increase, RVGWI (r = -0,581, p = 0,015 and r = -0,536, p = 0,027, respectively) and RVGWE (r = -0,779, p &amp;lt; 0,001 and r = -0,773, p &amp;lt; 0,001, respectively) decline significantly, whereas RVGWW (r = 0,735, p = 0,001 and r = 0,800, p &amp;lt; 0,001) increases. In our population, only RVGCW didn’t correlate significantly with high afterload (r= −0,304, p = 0,235 for mPAP, and r = -0,181, p = 0,488 for RVP). Conclusions New methods to evaluate RV function are crucial in patients with RV hemodynamic overload, since conventional echocardiographic parameters do not perform well. Novel echocardiographic assessment of RVMW are associated with severity of PH in our population.

Aortic valve stenosis in familial hypercholesterolaemic: Should we systematically screen?

The optimal timing for mitral valve (MV) surgery in asymptomatic patients with primary mitral regurgitation (MR) remains a matter of debate. Myocardial contraction fraction (MCF) − the ratio of the left ventricular (LV) stroke volume to that of the myocardial volume − is a volumetric measure of LV myocardial shortening independent of size or geometry.To assess the relationship between MCF and outcome in patients with significant chronic primary MR due to prolapse managed in contemporary practice.Clinical, Doppler-echocardiographic and outcome data prospectively collected in 174 patients (mean age 62 years, 27% women) with significant primary MR and no or mild symptoms were analysed. The impact of MCF< or ≥30% on cardiac events (cardiovascular death, acute heart failure or MV surgery) was studied.During an estimated median follow-up of 49 (22–77) months, cardiac events occurred in 115 (66%) patients. The 4-year estimates of survival free from cardiac events were 21 ± 5% for patients with MCF <30% and 40 ± 6% for those with ≥30% (P < 0.001). MCF <30% was associated with a considerable increased risk of cardiac events after adjustment for established clinical risk factors, MR severity and current recommended class I triggers for MV surgery (adjusted hazard ratio: 2.33, 95% confidence interval: 1.51−3.58; P < 0.001). Moreover, MCF < 30% improved the predictive performance of models, with better global fit, reclassification and discrimination.MCF < 30% is strongly associated with occurrence of cardiac events in patients with significant primary MR due to prolapse. Further studies are needed to assess the direct impact of MCF on patient management and outcomes.

Clinical significance of myocardial contraction fraction in significant primary mitral regurgitation

BackgroundThe optimal timing for mitral valve (MV) surgery in asymptomatic patients with primary mitral regurgitation (MR) remains a matter of debate. Myocardial contraction fraction (MCF) − the ratio of the left ventricular (LV) stroke volume to that of the myocardial volume − is a volumetric measure of LV myocardial shortening independent of size or geometry. AimTo assess the relationship between MCF and outcome in patients with significant chronic primary MR due to prolapse managed in contemporary practice. MethodsClinical, Doppler-echocardiographic and outcome data prospectively collected in 174 patients (mean age 62 years, 27% women) with significant primary MR and no or mild symptoms were analysed. The impact of MCF< or ≥30% on cardiac events (cardiovascular death, acute heart failure or MV surgery) was studied. ResultsDuring an estimated median follow-up of 49 (22–77) months, cardiac events occurred in 115 (66%) patients. The 4-year estimates of survival free from cardiac events were 21±5% for patients with MCF <30% and 40±6% for those with ≥30% (P<0.001). MCF <30% was associated with a considerable increased risk of cardiac events after adjustment for established clinical risk factors, MR severity and current recommended class I triggers for MV surgery (adjusted hazard ratio: 2.33, 95% confidence interval: 1.51−3.58; P<0.001). Moreover, MCF<30% improved the predictive performance of models, with better global fit, reclassification and discrimination. ConclusionsMCF<30% is strongly associated with occurrence of cardiac events in patients with significant primary MR due to prolapse. Further studies are needed to assess the direct impact of MCF on patient management and outcomes.

МОБИЛЬНОЕ ПРИЛОЖЕНИЕ В ПРОГНОЗИРОВАНИИ СИСТОЛИЧЕСКОЙ ФУНКЦИИ ЛЕВОГО ЖЕЛУДОЧКА ПРИ ЛЕЧЕНИИ РАКА МОЛОЧНОЙ ЖЕЛЕЗЫ АНТРАЦИКЛИНАМИ

Purpose. To evaluate the effect of complex treatment of breast cancer (BC) on the parameters of systolic myocardial function, and the efficiency of the prescription of cardiotropic therapy (CT) – a fixed combination of valsartan and carvedilol – in the prevention of the identified changes. To develop a mobile application, namely, an electronic statistical calculator for calculating the left ventricular ejection fraction by Simpson during BC treatment with anthracyclines, using the baseline anthropometric and instrumental data of the patient. Methods. We evaluated the cardiovascular health of 100 women who received complex treatment of BC. The patients were divided into three groups, depending on the presence of arterial hypertension and the prescription of CT. In the study, all women received a complex evaluation of the cardiovascular health at the beginning and at the end of BC treatment Results. In the non-CT group af ter the end of complex BC treatment the following was found: a decrease in the shortening fraction (FS) from 41.0 (38.0; 45.0)% to 38.0 (35.0; 43.0)%, (p &lt; 0.05), in ejection fraction (EF) by Teinholz from 72.0 (69.0; 76.0)% to 68.0 (64.0; 73.0)%, (p &lt; 0.05); in ejection fraction by Simpson from 66.0 (62.0; 71.0)% to 60.0 (57.0; 66.0)%, (p &lt; 0.05); an increase in the vagosympathetic interaction LF/HF index (ratio of lowfrequency (LF) to high-frequency (HF) components) from 0.8 (0.7; 1.0) to 1.05 (0.8; 1.2), (p &lt; 0.05); reduction of brachial artery diameter change from 12.5 (11.0; 16.0)% to 9.0 (6.0; 12.0)%, (p &lt; 0.05). A model of the prognosis of EF by Simpson during BC treatment was proposed, which included a total dose of doxorubicin calculated per body surface area, early diastolic rate of transtricuspid blood flow, diameter of the trunk of the pulmonary artery, the rate of circular shortening of myocardial fibers, thickness of the intima-media complex of the left carotid arteries, HF, % of brachial artery diameter change. The prognosis model formed the basis for the development of the mobile application for predicting left ventricular systolic function during BC treatment with anthracyclines. We proposed a model for prediction of LVEF by Simpson against during breast cancer treatment, which included the total doxorubicin dose calculated per body surface area, early diastolic rate of transtricuspidal blood flow, pulmonary artery trunk diameter, myocardial fiber circular shortening rate, left carotid artery intima-media complex thickness, HF, percentage of brachial artery diameter change. The prognostic model formed the basis for the development of the mobile application for predicting left ventricular systolic function during BC treatment with anthracyclines.

Development of a Zebrafish Larvae Model for Diabetic Heart Failure With Reduced Ejection Fraction

Diabetes mellitus (DM)-associated heart failure (HF) causes high morbidity and mortality. In this study, we established a zebrafish larvae model for in vivo research on diabetic HF. DM-like phenotypes were induced by treating zebrafish larvae with a combination of D-glucose (GLU) and streptozotocin (STZ). HF was induced by treatment with terfenadine (TER), a potassium channel blocker. Additionally, myocardial contractility, motility, and viability were evaluated. The zebrafish larvae treated with a combination of GLU and STZ showed significantly higher whole-body glucose concentrations, lower insulin levels, and higher phosphoenolpyruvate carboxykinase levels, which are markers of abnormal glucose homeostasis, than the group treated with only GLU, with no effect on viability. When treated with TER, DM zebrafish showed significantly less myocardial fractional shortening and more irregular contractions than the non-DM zebrafish. Furthermore, in DM-HF with reduced ejection fraction (rEF) zebrafish, a significant increase in the levels of natriuretic peptide B, a HF biomarker, markedly reduced motility, and reduced survival rates were observed. We established a DM-HFrEF zebrafish model by sequentially treating zebrafish larvae with GLU, STZ, and TER. Our findings indicate the potential utility of the developed zebrafish larvae model not only in screening studies of new drug candidates for DM-HFrEF but also in mechanistic studies to understand the pathophysiology of DM-HFrEF.

Myocardial Contraction Fraction is not a Predictor of Clinical Outcomes in Acute Systolic Heart Failure: A Brief Report.

The utility of myocardial contraction fraction (MCF), a volumetric measure of myocardial shortening, has not been well evaluated in patients with systolic heart failure (SHF). A single-center, retrospective cohort study of all adults admitted with acute SHF from 2013 to 2018 at an academic medical center. A chart review was performed to identify key echocardiographic transthoracic echocardiogram (TTE), laboratory, and demographic characteristics. MCF was calculated based on M-mode measurements of estimated stroke volume and myocardial volume based on admission TTE. The primary outcome was 30-day combined all-cause readmission/mortality and 365-day all-cause mortality. A total of 1282 patients were analyzed. The 30-day composite outcome occurred in 310 patients (24.2%), and all-cause death at 365 days occurred in 375 patients (29.3%). There was a weak correlation between the visually estimated ejection fraction (EF) and MCF (r = 0.356, P < 0.001). Neither MCF nor EF was associated with either component of the primary outcome. Other parameters on TTE that were associated with higher risk of primary outcome were higher tricuspid regurgitation (TR) velocity, larger left atrial (LA) diameter, and moderate or greater TR and mitral regurgitation (MR). Echocardiographic predictors of postdischarge adverse events among patients hospitalized with acute SHF include higher TR velocity, larger LA diameter, and at least moderate MR or TR. MCF does not correlate well with visually assessed EF among patients with acute SHF, and neither MCF nor EF provides prognostic information in this population.

Abstract 15: Hypoxia As Therapy For Mitochond​Rial Injury Following Cardiac Arrest

Introduction: Mitochondrial injury occurs following cardiac arrest (CA) and contributes to myocardial stunning and anoxic brain injury. Hypoxia has been proposed as a therapeutic strategy for neurodegenerative diseases associated with mitochondrial respiration defects, but its benefits in the post-CA setting remain unexplored. Here, we hypothesized mild hypoxia as therapy for post-CA mitochondrial injury. Methods and Results: Mice underwent brief asystolic CA (12 min) followed by cardiopulmonary resuscitation (CPR). One hour following successful CPR, mice were randomized to receive a brief episode (6 hours) of hyperoxia (33% O 2 ), normoxia (21% O 2 ), or hypoxia (10% O 2 ) in an environmental chamber. Post exposure, the mice were returned to room air (21% O 2 ). Hypoxia improved myocardial fractional shortening compared to normoxia and hyperoxia (Hypoxia: 45.6±2.3 %, Normoxia: 40.0±0.8 %, Hyperoxia: 29.0±4.0 %, n=5, P&lt;0.05, respectively). Hypoxia also elevated neurological scores (Hypoxia: 8.4±1.3, Hyperoxia: 5.6±1.2, n=5, P&lt;0.05) 48 hours post CA compared to hyperoxia. Ten-day survival was prolonged by hypoxia (Hypoxia: 87.5 %, Normoxia: 62.5 %, Hyperoxia: 12.5 %, n=10, P&lt;0.05, respectively). Hypoxia also improved mitochondrial function (28% increase in basic oxygen consumption and 49% increase in ATP-related oxygen consumption, n=3, P&lt;0.05, respectively) and a 20% decrease in ROS production (n=6, P&lt;0.05) compared to normoxia. Conclusion: This study has two important findings: First , we demonstrate that oxygen availability in the early post-CA period is a critical determinant of long-term post-CA outcomes. Second , we show that mild hypoxic therapy in the early post-CA period improves early mitochondrial function and long-term post-CA outcomes. These findings reveal an important oxygen-dependent therapeutic window following resuscitation from CA that has implications for post-CA critical care.

Abstract 12077: Impact of Overweight and Obesity on Left Ventricular Structure and Function in a Community Dwelling Cohort Free of Cardiovascular Disease

Introduction: Obesity is associated with excess cardiovascular morbidity and mortality as well as structural and functional differences in left ventricular (LV) mass (LVM), end-diastolic volume (LVEDV), and stroke volume despite indexation. Hypothesis: We hypothesize that overweight and obesity impact LV structure and function in a healthy community dwelling cohort. Methods: Framingham Offspring study participants (N=678, 62%F; 65±9y) free of any history of hypertension, myocardial infarction, heart failure, or CMR wall-motion abnormality and underwent bSSFP CMR at 1.5T. They were stratified by sex and body mass index (BMI) category (normal weight =18.5 to 24.9; overweight =25.0 to 29.9; obese ≥30 kg/m 2 ). LVM was measured from contiguous short-axis images, then indexed to height (HT, m), body surface area (BSA, m 2 ), and weight (WT, kg). We calculated myocardial contraction fraction (MCF), a marker of LV myocardial shortening, as LV stroke volume divided by LV myocardial volume. The ratio of LVM/LVEDV was used as a measure of LV concentricity to evaluate LV structure. Results: The Table shows MCF, LV concentricity, and indexed LVM (LVMi) stratified by BMI. WT-indexation resulted in a declining LVMi with increasing BMI in both men and women. However, indexation to HT showed an increasing LVMi with higher BMI. BSA-indexation remained consistent across BMI categories in both men and women. MCF decreased and concentricity increased with increasing BMI in both sexes. Conclusion: The association of LVMi with BMI varies by indexation method. In a healthy, community-dwelling cohort, BSA yields “consistent” LVM indexation across BMI categories. However, MCF decreased, and concentricity increased with increasing categories of BMI. These adverse alterations of MCF and concentricity may provide insight into obesity-related LV remodeling, whereas consideration of LVM alone may not. These data lay the groundwork for further outcomes analyses in this population.

Abstract 9614: Association Between Myocardial Contraction Fraction and Heart Failure Subtypes in the Multi-Ethnic Study of Atherosclerosis (MESA)

Introduction: Myocardial contraction fraction (MCF) is a non-ejection fraction volumetric measure of myocardial shortening which has been associated with incident heart failure (HF) including in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. However, less is known regarding MCF’s prediction of HF subtypes. Methods: This analysis included men and women aged 45-84 free of clinical cardiovascular disease who underwent cardiac magnetic resonance imaging (cMRI) during the baseline MESA examination and who had data regarding incident adjudicated definite or probable HF events. MCF was calculated using cMRI measurements and defined as the ratio of stroke volume to myocardial volume. HF subtypes were divided into HF with ejection fraction (EF) &lt; 50% (HF EF &lt; 50%, including HF with reduced EF (EF ≤ 40%) and HF with mildly reduced EF (EF 41-49%) and HF with preserved EF (HFpEF, EF ≥ 50%). Cox proportional hazards regression was used to examine the association between MCF and incident HF subtype per decile increase in MCF. Event time was defined as time of first defined HF subtype, and censoring occurred at death or end of follow-up. After an incident HF event, participants were not at risk for another HF subtype. Covariates adjusted for were age, gender, race-ethnicity, education, body-mass index, tobacco and alcohol use, systolic blood pressure (BP), diabetes, physical activity, total cholesterol, and BP and lipid lowering drug use. Results: Among 4,983 participants (mean age 61, 52% female, 61% non-White) over a maximum of 18 years follow-up, there were 275 incident HF events (142 HF EF &lt; 50%, 113 HFpEF, 20 unknown EF). MCF differed across HF status (p&lt;0.001) . Participants without incident HF had a higher mean MCF (0.65) compared to HFpEF (0.62), HF EF &lt; 50% (0.53), and unknown EF (0.52). The adjusted risk of any HF was reduced (HR 0.86, 95% CI 0.82, 0.91) per decile increase of MCF. MCF was strongly associated with incident HF EF &lt; 50% (adjusted HR 0.80, CI 0.74, 0.86) but was not associated with HFpEF (adjusted HR 0.98, CI 0.91, 1.05). Conclusions: In a multi-ethnic cohort, increasing MCF is associated with a decreased risk of incident HF EF&lt;50%. MCF is not significantly associated with incident HFpEF, suggesting different etiologic pathways for these two HF subtypes.

Post-systolic shortening index by echocardiography evaluation of dyssynchrony in the non-dilated and hypertrophied left ventricle

Abstract Background Post-systolic shortening index (PSI) is defined as myocardial shortening that occurs after aortic valve closure, and is an emerging measure of regional LV contractile dysfunction. PSI measurement variability amongst software vendor and its relationship with mechanical dyssynchrony and mechanical dispersion index (MDI) remains unknown. We evaluated PSI by speckle-tracking echocardiography from several vendors in patients with increased left ventricular wall thickness, and associations with MDI. Methods This is a prospective cross-sectional study of 70 patients (36 hypertrophic cardiomyopathy [HCM], 18 cardiac amyloidosis and 16 healthy controls) undergoing clinically indicated echocardiography. PSI was measured using QLAB/aCMQ (Philips), QLAB/LV auto-trace (Philips), EchoPAC (GE), Velocity Vector Imaging (Siemens), and EchoInsight (EPSILON) software packages, and calculated as 100% × (post systolic strain − end-systole strain)/post systolic strain. Results There was a significant difference in mean PSI among controls 2.1±0.6%, HCM 6.1±2.6% and cardiac amyloidosis 6.8±2.7% (p&amp;lt;0.001). Variations between software vendors were significant in patients with pathologic increases in LV wall thickness (for HCM p=0.03, for amyloidosis p=0.008), but not in controls (p=0.11), as seen in Figure 1. Furthermore, there were moderate correlations between PSI and both MDI (r=0.77) and left ventricular global longitudinal strain (r=0.69), as seen in Figure 2. Conclusion PSI was greater in HCM and cardiac amyloidosis patients than controls, and a valuable tool for dyssynchrony evaluation, with moderate correlations to MDI and strain. However, there were significant variations in PSI measurements by software vendor especially in patients with pathological increase in LV wall thickness, suggesting that separate vendor-specific thresholds for abnormal PSI are required. Funding Acknowledgement Type of funding sources: None.

Heterozygous APOE ε4 carriage associates with improved myocardial efficiency in older age

Abstract Background Carriage of the ancestral APOE ε4 allele confers a risk of developing Alzheimer's and coronary artery disease, but its persistence in human populations also suggests some potential survival advantages. To date it remains unclear whether APOE ε4 carriage independently associates with a better or worse long-term cardiac phenotype. Purpose Using data from the 1946 National Survey of Health and Development (NSHD) birth cohort, we investigated whether APOE ε4 carriage associates with adverse or beneficial left ventricular (LV) size and function parameters by echocardiography in older age. Methods Based on the presence or absence of APOE ε4, genotypes were divided into: non-APOE ε4 (ε2ε2, ε2ε3, ε3ε3), heterozygous-APOE ε4 (ε2ε4 and ε3ε4) and homozygous-APOE ε4 (ε4ε4). Echocardiographic data at 60–64 years included: left ventricular ejection fraction (LV EF), E/e', systolic and diastolic LV posterior wall and interventricular septal thickness (LVPWTs/d, IVSs/d), and body-surface area indexed LV mass (LVmassi) and myocardial contraction fraction (MCFi). Generalized linear models explored associations between APOE ε4 genotypes as exposures and echocardiographic biomarkers as outcomes. As a combination of gene variants, APOE ε genotype is expected to be an instrumental variable and therefore unconfounded. Thus, Model 1 was unadjusted. To obtain more precise regression estimates, Model 2 was adjusted for factors associated with the outcome, namely sex and socio-economic position (SEP). To explore the mechanistic pathway downstream of APOE ε genotype but upstream of the echocardiographic outcomes, subsequent models were adjusted for mediators as follows: Model 3 for body mass index, Model 4 for the presence of cardiovascular disease (CVD), Model 5 for diabetes, Model 6 for high cholesterol and Model 7 for hypertension. Results 1464 participants were included. Compared to non-APOE ε4 and homozygous groups, heterozygous-APOE ε4 individuals had similar cardiac phenotypes in terms of EF, E/e', LVPWTs/d, IVSs/d and LVmassi but had a 7% higher MCFi 95% confidence interval [CI]: 1%-13%, p=0.017) which persisted even after adjustment for sex and SEP (95% CI 1%-12%, p=0.026) that was attenuated to 6% after adjustment for CVD (95% CI 0–13% p=0.050) and hypertension (95% CI 1–13% p=0.022). Conclusion The heterozygous-APOE ε4 state associates with improved myocardial shortening in older age resulting in greater LV stroke volume generation per 1 mL of myocardium. As we found no association between APOE ε4 carriage and LVPWTs/d, IVSs/d or LVmassi, MCFi enhancement may be mediated by improved myocardial energetics and contractility, with calcium and androgens potentially implicated, rather than through pathological ventricular thickening. Although a dose relationship is normally expected with ε4 carriage, any benefit from increased energetics and contractility is likely to be counterbalances by the higher risk of CVD and cardiovascular risk factors. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): UK Medical Research Council British Heart Foundation