Endocardial Circumferential Strain Research Articles

The clinical application of longitudinal layer specific strain as a diagnostic and prognostic instrument in ischemic heart diseases: A systematic review and meta-analysis.

2-dimensional Speckle-Tracking Echocardiography, to obtain longitudinal layer specific strain (LSS), has recently emerged as a novel and accurate non-invasive imaging technique for diagnosis as well as for prediction of adverse cardiac events. This systematic review and meta-analysis aimed to give an overview of the possible clinical implication and significance of longitudinal LSS. We conducted a systematic review and meta-analysis with all the studies involving layer specific strain in patients with ischemic heart disease (IHD). Of 40 eligible studies, 9 met our inclusion criteria. Studies that were included either investigated the prognostic value (n = 3) or the diagnostic value (n = 6) of longitudinal LSS. The pooled meta-analysis showed that longitudinal LSS is a significant diagnostic marker for coronary artery disease (CAD) in patients with IHD. Endocardial LSS was found to be a good diagnostic marker for CAD in IHD patients (OR: 1.28, CI95% [1.11-1.48], p < 0.001, per 1% decrease). Epicardial (OR: 1.34, CI95% [1.14-1.56], p < 0.001, per 1% decrease), Mid-Myocardial (OR: 1.24, CI95% [1.12-1.38], p < 0.001, per 1% decrease) and endocardial (OR: 1.21, CI95% [1.09-1.35], p < 0.001, per 1% decrease) LSS all entailed diagnostic information regarding CAD, with epicardial LSS emerging as the superior diagnostic marker for CAD in patients with SAP. Endocardial LSS proved to be the better diagnostic marker of CAD in patients with non-ST elevation acute coronary syndrome (NSTE-ACS). LSS was shown to be a good prognostic maker of adverse cardiac events in IHD patients. Two studies found endocardial circumferential strain to be the good predictor of outcome in CAD patients and when added to baseline characteristics. Epicardial LSS emerged as best predictor in acute coronary syndrome (ACS) patients. In patients with SAP, epicardial LSS was the stronger diagnostic marker while in NSTE-ACS patients, endocardial LSS was the stronger diagnostic marker. In addition, endocardial circumferential strain is the better predictor of adverse outcome in CAD patients whilst in ACS patients, epicardial LSS was found to be a better predictor of outcome.

Left and Right Myocardial Functionality Assessed by Two-Dimensional Speckle-Tracking Echocardiography in Cats with Restrictive Cardiomyopathy.

Simple SummaryThe endomyocardial form of restrictive cardiomyopathy, a primary disorder of the myocardium, is one of the diseases with poor prognosis in cats. While two-dimensional speckle-tracking echocardiography has been known to identify myocardial deformations, its function relative to cats with the endomyocardial form of restrictive cardiomyopathy has yet to be characterized. We hypothesized that both the left and right myocardial functional abnormalities may occur in cats with the endomyocardial form of restrictive cardiomyopathy, causing this disease pathophysiology and clinical status. In the current study, cats were assessed for layer-specific myocardial function (whole, endocardial, and epicardial) in the left ventricular longitudinal and circumferential directions, and right ventricular longitudinal direction, via two-dimensional speckle-tracking echocardiography. Our study indicated that cats with restrictive cardiomyopathy have reduced left ventricular myocardial function. Notably, left ventricular systolic circumferential endocardial strain and circumferential endocardial-to-epicardial strain ratio were lower in cats with restrictive cardiomyopathy. Furthermore, some right ventricular myocardial deformations were also differerent in cats with restrictive cardiomyopathy. Myocardial function assessed by two-dimensional speckle-tracking echocardiography could reveal left and right myocardial dysfunction.The endomyocardial form of restrictive cardiomyopathy (EMF-RCM), a primary disorder of the myocardium, is one of the diseases with poor prognosis in cats. We hypothesized that both the left and right myocardial functional abnormalities may occur in cats with EMF-RCM, causing this disease pathophysiology and clinical status. Out of the 25 animals included in this study, 10 were client-owned cats with EMF-RCM, and 15 were healthy cats. In this study, cats were assessed for layer-specific myocardial function (whole, endocardial, and epicardial) in the left ventricular longitudinal and circumferential directions, and right ventricular longitudinal direction, via two-dimensional speckle-tracking echocardiography (2D-STE). Cats with EMF-RCM had depressed left ventricular myocardial deformations both in systole (whole longitudinal strain, epicardial longitudinal strain, and endocardial circumferential strain) and diastole (early and late diastolic longitudinal strain rates, and late diastolic circumferential strain rate) compared to controls. Furthermore, some right ventricular myocardial deformations (systolic longitudinal strain in epicardial layers, and endocardial-to-epicardial strain ratio) were significantly differerent in cats with EMF-RCM. Myocardial function assessed by 2D-STE could reveal left and right myocardial dysfunction.

P1708 Analysis of ventricular mechanics in echo-guided endocardial radiofrequency septal ablation for hypertrophic obstuctive cardiomyopathy

Abstract Introduction Hypertrophic Obstructive Cardiomyopathy (HOCM) is an important cause of sudden death and heart failure, specially in young adults. Approximately 5% to 8% of patients are not suitable for transcoronary ablation, if myectomy is not feasible, Endocardial Radiofrequency Ablation of Septal Hypertrophy (ERASH) has shown acceptable efficacy and safety for left ventricular outflow tract (LVOT) gradient reduction. 20 ERASH cases have been reported in the literature. Case report 39 year old woman with diagnosis of HOCM, symptoms of dyspnea (NYHA III), and aborted sudden death as first clinical manifestation; a cardiac defibrillator was implanted. A transthoracic echocardiogram (TTE) revealed normal left ventricle (LV) ejection fraction, moderate mitral regurgitation (systolic anterior valve motion), basal inter-ventricular septal wall thickness of 20 mm generating a LVOT gradient of 51 mmHg. A coronary angiography showed inadequate septal branch anatomy to perform alcohol ablation. The patient refused myectomy. Heart Team decided to perform ERASH. Using a 3D Cardiac Mapping System and 2D Echocardiography, the basal interventricular septum received 50 Watts/50˚C radiofrequency ablation without any acute complication. Three days later, a TTE showed LVOT gradient 26 mmHg. The description of the LV mechanics is described on Table 1. Pre and post ERASH ventricular mechanics was analyzed including circumferential endocardial and mesocardial strain and strain rate, as well as longitudinal strain involved in the LV segments that received ERASH (Figure 1.) . Conclusion We report the analysis of ventricular mechanics after a successful case of ERASH, an alternative technique for treating HOCM. In our analysis, pre- ERASH longitudinal strain was significantly more negative at the basal anterior and anteroseptal segments than the other LV segments. This may be a predictor of focal LV remodeling at these segments in the future. Table 1. Pre ERASH Post ERASH Ventricular Segment Strain Strain Rate Strain Strain Rate Longitudinal Strain Basal Anteroseptal -14.4% -1.2 1/s -7% -0.6 1/s Endocardial Circumferential Strain Basal Anteroseptal -13.7% -1.9 1/s -32% -2.2 1/s Basal Anterior -44.6% -4.2 1/s -18.6% -1.6 1/s Mesocardial Circumferential Strain Basal Anteroseptal -7.7% -1.0 1/s -20.2% -1.2 1/s Basal Anterior -24.9% -1.7 1/s -13.8% -0.9 1/s Left ventricular mechanics pre and post ERASH. Abstract P1708 Figure 1.

Evaluation of myocardial mechanical changes in patients with acute myocardial infarction before and after percutaneous coronary intervention by speckle tracking technique

Objective To evaluate the changes of myocardial mechanics before and after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction(AMI) by ultrasonic speckle tracking technique, and investigate the recovery of left ventricular myocardium mechanics and the effects of common complications on the improvement of myocardial mechanics. Methods Sixty-two patients with AMI were examined by echocardiography within 12 hours, 1 week and 3 months after PCI. According to the complications the patients were divided into simple AMI group (21 cases), AMI with diabetes mellitus group (21 cases), and AMI with hypertension group (20 cases). Thirty healthy volunteers were selected as control group. Conventional echocardiographic parameters and left ventricular strain parameters were evaluated in all subjects. Results ①Left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic volume (LVEDV), and left ventricular end-systolic volume (LVESV) in each AMI group before PCI were greater than the control group (P 0.05 ). ③The degree of improvement of global longitudinal and circumferential endocardial strain in AMI with diabetes group were less than those in simple AMI group(P<0.05). The degree of improvement of global longitudinal endocardial strain in AMI with hypertension group was less than that in simple AMI group (P<0.05). Conclusions Patients with AMI have poor myocardial mechanics before PCI, especially those with diabetes mellitus; myocardial mechanics improves significantly 3 months after PCI; diabetes mellitus or hypertension affectes the improvement of myocardial mechanics in patients with AMI after PCI. Key words: Echocardiography; Acute myocardial infarction; Speckle tracking; Myocardial mechanics

Left Ventricular Strain Is Abnormal in Preclinical and Overt Hypertrophic Cardiomyopathy: Cardiac MR Feature Tracking.

Purpose To evaluate myocardial strain and circumferential transmural strain difference (cTSD; the difference between epicardial and endocardial circumferential strain) in a genotyped cohort with hypertrophic cardiomyopathy (HCM) and to explore correlations between cTSD and other anatomic and functional markers of disease status. Left ventricular (LV) dysfunction may indicate early disease in preclinical HCM (sarcomere mutation carriers without LV hypertrophy). Cardiac MRI feature tracking may be used to evaluate myocardial strain in carriers of HCM sarcomere mutation. Materials and Methods Participants with HCM and their family members participated in a prospective, multicenter, observational study (HCMNet). Genetic testing was performed in all participants. Study participants underwent cardiac MRI with temporal resolution at 40 msec or less. LV myocardial strain was analyzed by using feature-tracking software. Circumferential strain was measured at the epicardial and endocardial surfaces; their difference yielded the circumferential transmural strain difference (cTSD). Multivariable analysis to predict HCM status was performed by using multinomial logistic regression adjusting for age, sex, and LV parameters. Results Ninety-nine participants were evaluated (23 control participants, 34 participants with preclinical HCM [positive for sarcomere mutation and negative for LV hypertrophy], and 42 participants with overt HCM [positive for sarcomere mutation and negative for LV hypertrophy]). The average age was 25 years ± 11 and 44 participants (44%) were women. Maximal LV wall thickness was 9.5 mm ± 1.4, 9.8 mm ± 2.2, and 16.1 mm ± 5.3 in control participants, participants with preclinical HCM (P = .496 vs control participants), and participants with overt HCM (P < .001 vs control participants), respectively. cTSD for control participants, preclinical HCM, and overt HCM was 14% ± 4, 17% ± 4, and 22% ± 7, respectively (P < .01 for all comparisons). In multivariable models (controlling for septal thickness and log-transformed N-terminal brain-type natriuretic peptide), cTSD was predictive of preclinical and overt HCM disease status (P < .01). Conclusion Cardiac MRI feature tracking identifies myocardial dysfunction not only in participants with overt hypertrophic cardiomyopathy, but also in carriers of sarcomere mutation without left ventricular hypertrophy, suggesting that contractile abnormalities are present even when left ventricular wall thickness is normal. © RSNA, 2018 Online supplemental material is available for this article.

Echocardiographic strain in hypertrophic cardiomyopathy and hypertensive left ventricular hypertrophy.

The myocardial structure differs between secondary left ventricular hypertrophy (LVH) and hypertrophic cardiomyopathy (HCM). We investigated left ventricular function of these two types of hypertrophy using multilayer strain analysis with two-dimensional echocardiography. Transthoracic echocardiography (Vivid-E9) was performed in 240 patients with preserved left ventricular ejection fraction (LVEF ≥50%) and with either HCM (n=80, 63 men, age 49.8±14.1years), hypertensive LVH (n=80, 63 men, age 51.4±13.3years) or normal blood pressure and left ventricular structure (n=80, 63 men, 50.8±12.4years). Quantitative multilayer longitudinal strain (LS), circumferential strain (CS), and radial strain (RS) were analyzed. The ratio of endo-/epi-myocardial strain was calculated. Longitudinal strain was significantly (P<0.001) lower in HCM patients than normal controls (15.2±4.2% vs 23.1±2.7%), especially in hypertrophic segments (14.5±4.4% vs 17.2±3.2% in nonhypertrophic segments, P<0.01). LS was lower in patients with hypertensive LVH, similarly in all left ventricular segments (20.7±3.7%, P<0.001 vs controls). CS was lower in the mid- and epicardium (P<0.01), but not endocardium in HCM (P=0.4), and preserved in all myocardial layers in hypertensive LVH. The endo-/epi-myocardial ratios of both LS and CS were higher in HCM than hypertensive LVH (P<0.01). RS was higher (P<0.01) in HCM than hypertensive LVH and controls. Endocardial CS and global RS were correlated with LVEF (r≥0.32, P<0.01). Hypertrophic cardiomyopathy patients had marked reductions in LS and CS, whereas patients with hypertensive LVH had less reduction in LS and preserved CS. The increased endo-/epi-myocardial ratios of LS and CS may be useful in differentiating HCM from hypertensive LVH.

Layer-specific myocardial function in asymptomatic cats with obstructive hypertrophic cardiomyopathy assessed using 2-dimensional speckle-tracking echocardiography.

BackgroundHypertrophic cardiomyopathy (HCM), a primary disorder of the myocardium, is the most common cardiac disease in cats. However, determination of layer‐specific myocardial function with 2D speckle‐tracking echocardiography in cats with asymptomatic HCM has not yet been reported.ObjectivesTo quantitatively measure layer‐specific myocardial function of asymptomatic cats with HCM.AnimalsTen client‐owned, asymptomatic cats with obstructive HCM and 13 healthy cats.MethodsA retrospective, case‐control study. Cats underwent assessment of layer‐specific myocardial function (whole, endocardial, and epicardial) in the longitudinal and circumferential directions by using 2D speckle‐tracking echocardiography.ResultsLongitudinal strains were significantly lower in cats with HCM than controls in the whole (−15.5% vs −19.1%), endocardial (−18.3% vs −21.8%), and epicardial (−13.1% vs −16.8%) layers. Circumferential strains in whole and epicardial layers also were significantly lower in cats with HCM as compared with controls (−15.0% vs −20.2% and − 4.4% vs −9.4%, respectively). However, no significant difference was found between cats with HCM and controls in the global circumferential strain in the endocardial layer (−31.2% vs −34.2%). The circumferential endocardial‐to‐epicardial strain ratio was significantly higher in cats with HCM than in controls (6.1 vs 3.5).Conclusions and Clinical ImportanceLayer‐specific myocardial function assessed by 2D speckle‐tracking echocardiography differed in asymptomatic cats with obstructive HCM compared to controls despite their apparently normal systolic function, as determined by conventional echocardiography. The maintained endocardial circumferential strain and higher circumferential endocardial‐to‐epicardial strain ratio may reflect compensation for occult systolic dysfunction in cats with obstructive HCM.

Cardiac magnetic resonance characteristics in young survivors of aborted sudden cardiac death

PurposeWe aimed to identify and assess cardiac abnormalities by cardiovascular magnetic resonance (CMR) in a non-ischaemic aborted sudden cardiac death (SCD) population and to establish possible predictors of SCD. MethodsThirty-six consecutive SCD survivors [median age 37.6 years (IQR 24.1-43.2), 31% female] with no previous cardiac history or evidence of ischaemic heart disease underwent CMR on day 6 (IQR 4-10) after admission. Data on ventricular volumes and the extent of late gadolinium enhancement (LGE) were collected. Systolic strain analysis was performed using feature tracking software. ResultsLeft ventricular (LV) and right ventricular (RV) indexed diastolic volumes were 92.9 ± 28.4 ml/m2 and 94.1 ± 29 ml/m2, respectively. LV ejection fraction (EF) and RV EF were 56.8 ± 10.7% and 53.7 ± 10.7%, respectively. Global peak endocardial longitudinal, circumferential, and radial strain were −17.9 ± 4.28%, −23.2 ± 5.8%, and 32.8 ± 10.6%, respectively. Compared to normal range, global longitudinal endocardial strain, longitudinal epicardial strain, circumferential endocardial strain, radial strain, and circumferential endocardial strain rate were impaired. Median volume of LGE was 0.25% (IQR 0.12-1.12) of the LV myocardium with highest prevalence in the inferolateral wall. Patients with cardiomyopathy diagnosis (n = 16) had lower LV strain rate compared to patients without cardiomyopathy (n = 20). ConclusionsCMR findings in young patients with aborted SCD due to non-ischaemic heart disease seem to be minor. Although only present in small amounts, LGE appears to have a predilection towards the inferolateral wall in this population.

Clinical study on assessment of left ventricular systolic function in patients with hypertrophic cardiomyopathy by vector velocity imaging

Objective To analyze the strains of patients with hypertrophic cardiomyopathy (HCM) by vector velocity imaging(VVI), and to identify abnormal early systolic function. Methods Forty patients with HCM (HCM group) and 25 healthy subjects (control group) were enrolled. Standard two-dimensional echocardiography was performed. Left ventricular ejection fraction (LVEF), diameters and wall thickness were measured. Peak systolic strains in all directions and their time to peak were analyzed off-line. Results ①All but the endocardial circumferential strain were apparently smaller in HCM group than those in the control group(P<0.000 1). The difference was greater in long axis than that in short axis. ②The HCM group maintained the characteristics of strain gradient as the control group, including the endocardium-epicardium gradient with endocardial strains was significantly greater than epicardial ones and the base-apex gradient, among which epicardial longitudinal strain decreased from the base to the apex and endocardial circumferential strain increased toward the apex. ③The HCM group suffered significant dyssynchrony in terms of strain and rotation, with greater changes in longitudinal than in short axis, in epicardium than in endocardium. Conclusions VVI offers an overall assessment of regional and global left ventricular systolic function, including longitudinal and circumferential strain. Moreover, it can be used to evaluate subclinical systolic dysfunction and dyssynchrony in patients with HCM. Key words: Echocardiography; Ventricular function, left; Cardiomyopathy, hypertrophic; Strain; Vector velocity imaging

In-Depth Insight Into the Mechanisms of Cardiac Dysfunction in Patients With Childhood Cancer After Anthracycline Treatment Using Layer-Specific Strain Analysis.

Anthracycline cardiotoxicity affects clinical outcomes, and its early detection using methods that rely on conventional echocardiography, such as left ventricular ejection fraction (LVEF) is difficult. This study aimed to evaluate the characteristics and the differences in cardiac dysfunction among childhood cancer survivors in 3 age groups using layer-specific strain analysis in a wide age range.Methods and Results:The 56 patients (median age: 15 [range: 6.8-40.2] years) who had been treated with anthracycline for childhood cancer were divided into 3 age groups (C1: 6-12 years, C2: 13-19 years, C3: 20-40 years) after anthracycline treatment, and 72 controls of similar ages were divided into 3 corresponding groups (N1, N2, and N3). Layer-specific longitudinal strain (LS) and circumferential strain (CS) of 3 myocardial layers (endocardium, midmyocardium, and epicardium) were determined using echocardiography. Myocardial damage had not occurred yet in C1. Endocardial CS at the basal level was less in C2 than in N2. Endocardial CS at all levels and midmyocardial CS at the basal and papillary levels were lower in C3 than in N3. LVEF and LS were not significantly different between patients and controls. Among survivors of childhood cancer, impaired myocardial deformation starts in adolescence and extends from the endocardium towards the epicardium and from the base towards the apex with age. These findings are a novel insight into the time course of anthracycline cardiotoxicity.

Abstract P353: Attenuation of Cardiac Fibrosis, Hypertrophy and Myopathy by AT2R Agonist NP-6A4

Adverse cardiac remodeling (hypertrophy, fibrosis and myopathy) underlies cardiac dysfunction and heart failure. Male Zucker obese (ZO:fa/fa) rat that suffers from cardiac dysfunction, adverse remodeling, and heart failure with preserved ejection fraction is a useful model to study the effects of cardioprotective drugs. We reported that NP-6A4 (Novopyxis Inc. Cambridge, MA), a peptide agonist of the Angiotensin II Type 2 Receptor (AT2R), protected mouse cardiomyoblast HL-1 cells and human coronary artery vascular smooth muscle cells (hCAVSMCs) from acute nutrient serum deficiency stress better than β-AR-Blockers, ARBs, and AT2R agonist CGP42112A. This effect was inhibited by AT2R-specific antagonist PD123319, confirming that NP-6A4 acts through AT2R. AT2R is a cardiac and vascular reparative molecule that protects the heart and vasculature from structural damage and fibrosis. No current drugs increase AT2R expression. We report that NP-6A4 treatment (1μM) increased AT2R mRNA (up to 4 fold; p≤0.05) in hCAVSMCs and human coronary artery endothelial cells (up to 8 fold; p≤0.05). This effect was inhibited by PD123319 (10 μM). Treatment of 11-week old male ZO rats with heart disease with NP-6A4 (1.8mg/kg/day in saline, delivered once daily subcutaneously; N=7) increased cardiac AT2R expression and mitigated cardiac dysfunction and adverse remodeling. Quantitative RT-PCR and immunohistochemistry analysis showed that 2 weeks of NP-6A4 treatment increased cardiac AT2R mRNA (up to 9 fold) and protein (1.5-3 fold) compared to controls (N=6) receiving saline (p&lt;0.01). NP-6A4 treatment improved cardiac parameters; endocardial circumferential strain (p≤0.05), myocardial performance index (MPI) (p≤0.005), and E/E’ ratio (p≤0.002). NP-6A4 treatment also increased cardiac capillary density (118% compared to saline treatedl; p≤0.002), and reduced interstitial fibrosis (77% compared to saline treated; p≤0.039.) At 19-weeks (after 8 weeks of treatment), cardiac tissues from 5 out of 6 control rats exhibited regions of myopathy. Only 2 out 7 NP-6A4 treated rats exhibited similar levels of myopathy in the heart. We propose that NP-6A4 attenuates adverse remodeling and improves cardiac function by increasing AT2R expression in cardiac cells.

Diagnostic capability of feature-tracking cardiovascular magnetic resonance to detect infarcted segments: a comparison with tagged magnetic resonance and wall thickening analysis

To examine the diagnostic capabilities of feature-tracking cardiovascular magnetic resonance (FT-CMR), tagged cine magnetic resonance (MR), and wall thickening (WT) analyses to detect infarcted segments in patients with established myocardial infarction (MI). Twenty patients with established MI were selected retrospectively and the peak endocardial circumferential strain (CS) was quantified based on the 16-segment model. According to CMR with late gadolinium enhancement, segments were categorised as transmural MI, subendocardial MI, and no MI. A total of 320 segments (62 transmural MI, 50 subendocardial MI, and 208 no MI) were analysed. Peak endocardial CS was significantly lower for transmural MI compared with subendocardial MI (p<0.05) and no MI (p<0.001). Cut-off values of -11.2% for CS by FTCMR, -10.9% for CS by tagged MR, and 23.8% for %WT, differentiated between infarcted and non-infarcted segments with a sensitivity of 72%, 71%, and 56%; specificity of 71%, 75%, and 67%; accuracy of 72%, 73%, and 63%; positive predictive value of 57%, 60%, and 48%; negative predictive value of 83%, 83%, and 74%; and an area-under-the-curve of 0.77, 0.79, and 0.64, respectively. FT-CMR was diagnostically superior to %WT, and could differentiate between subendocardial and transmural MI. Unlike tagged MR, FT-CMR did not require the acquisition of additional sequences.

Erratum to: Intra-procedural determination of viability by myocardial deformation imaging: a randomized prospective study in the cardiac catheter laboratory.

The benefit of revascularization for functional recovery depends on the presence of viable myocardial tissue. Myocardial deformation imaging allows determination of myocardial viability. In a first approach, we assessed the optimal cutoff value to determine preserved viability by layer-specific echocardiographic myocardial deformation imaging at rest and low-dose dobutamine (DSE) echocardiography: regional endocardial circumferential strain (eCS) <−19% at rest was as accurate as eCS at DSE. In a main study, 123 patients (66% men, age 59 ± 6 years) with relevant coronary stenoses and corresponding severe regional myocardial dysfunction were included and randomized in 2 groups after coronary angiography: group A: intra-procedural myocardial deformation imaging in the cardiac catheter laboratory (CLab), determination of myocardial viability by regional eCS <−19%, in case of positive viability immediate coronary intervention in the same session. Group B: two-step determination of myocardial viability by cardiovascular magnetic resonance (CMR), in case of positive viability coronary intervention. After 18 months follow-up an analysis of the endpoints regarding cardiovascular events, left ventricular (LV) function, and comparison of cost was performed. Group A (N = 61) and group B (N = 62) showed no differences concerning localization of the coronary stenosis, comorbidities, or medical therapy. Cardiovascular events at 18-month follow-up were as follows: group A 13% (N = 10) vs. group B 14% (N = 9, p = 0.288); improvement of LV function: group A: +7 ± 2% vs. group B: +7 ± 3%, p = 0.963; costs: group A: 3096 Dollar vs. group B: 6043 Dollar, p < 0.001. Intra-procedural determination of myocardial viability by myocardial deformation imaging in the CLab is feasible, safe, and cost effective and may become an emerging alternative to the current practice of two-stage viability diagnostics.

Cardiovascular Protective Effects of AT2R Activation by Peptide Drug NP‐6A4

Introduction and ObjectiveLiterature shows that elevated Angiotensin II Type 2 receptor (AT2R) expression is cardiovascular reparative and mediates protection from hypertension, as well as vascular and renal injury. AT2R is a member of the anti‐inflammatory branch of the renin‐angiotensin system (RAS). Clinically, loss of AT2R expression in men due to the intronic G1675A or A1818T polymorphism is associated with impaired kidney function, pulse pressure and increased arterial stiffness. Given the pathological consequences of the loss of AT2R expression there is need for a drug that can increase AT2R gene (Agtr2) expression to mitigate cardiovascular damage. Currently there are no FDA‐approved drugs that meet these parameters. NP‐6A4 is a peptide agonist for AT2R, recently developed by Novopyxis Inc. We have shown that NP‐6A4 increases the viability of nutrient‐stressed mouse and human cardiovascular cells. Chemotherapeutic agents such as anthracyclins are inducers of cardiotoxicity. Therefore we investigated whether NP‐6A4 can protect cardiac cells from Doxorubicin (Dox; an anthracyclin) induced toxicity. To test the translational potential of a treatment paradigm that utilizes NP‐6A4 to improve cardiac functions and mitigate cardiac structural damage, we investigated the effects of NP‐6A4 treatment in Male Zucker Obese (ZO‐M) rats, a model for heart failure with preserved ejection fraction and cardiomyopathy.MethodsMTS assay (BioVision) was used to determine the effect of Dox treatment (0.5–2 μM) with and without co‐treatment with NP‐6A4 (1μM) on the survival of H9c2 cardiomyoblasts. To evaluate the effect of NP‐6A4 on cardiac structure and function, we treated 11‐week‐old ZO‐M rats that had fully developed cardiovascular disease with NP‐6A4 (1.8mg/kg/day by subcutaneous delivery). Echocardiography was used to assess cardiac function parameters. Cardiac architecture, hypertrophy, capillary density and fibrosis were assessed by staining using hematoxylin and eosin, Helix pomatia agglutinin (HPA), isolectin B4 (IB4) and Picrosirius Red (PSR) respectively. Expression levels of AT2R in the heart were assessed by quantitative RT‐PCR.Results24‐hour Dox treatment of H9c2 cardiomyoblasts suppressed cell viability (78% for 2μM vs untreated) and co‐treatment with NP‐6A4 restored cell survival. NP‐6A4 improved several cardiac parameters including endocardial circumferential strain (p≤0.05), myocardial performance index (MPI) (p≤0.005), and E/E' ratio (p≤0.002). NP‐6A4 reduced cardiomyocyte hypertrophy and fibrosis, and increased capillary density (p≤0.05). Importantly, cardiac Agtr2 (AT2R) mRNA levels were increased by about 9‐fold in NP‐6A4 treated rats vs. saline treated rats. Histopathology staining revealed regions of micro‐infarcts present in the saline group which were largely absent in the NP‐6A4 treated animals.ConclusionNP‐6A4 could mitigate Dox‐induced cardiac cell toxicity in vitro. NP‐6A4 also improved cardiac functions in a murine model of heart failure with preserved ejection fraction and cardiomyopathy, decreased risk of cardiac event (as measured by E/E'), mitigated myocardial structural damage, and improved cardiac vascularization. To our knowledge, NP‐6A4 is the first AT2R agonist that can increase cardiac AT2R expression. Based on these observations, we propose that this therapeutic candidate has the potential to treat chemotherapy‐induced cardiotoxicity as well as heart failure.Support or Funding InformationThis work was supported by NIH grant 1R01HL118376‐01 (LP), a small grant from Novopyxis Inc (LP), and Research Services facilities of HSTMVH.

Intra-procedural determination of viability by myocardial deformation imaging: a randomized prospective study in the cardiac catheter laboratory.

The benefit of revascularization for functional recovery depends on the presence of viable myocardial tissue. Myocardial deformation imaging allows determination of myocardial viability. In a first approach, we assessed the optimal cutoff value to determine preserved viability by layer-specific echocardiographic myocardial deformation imaging at rest and low-dose dobutamine (DSE) echocardiography: regional endocardial circumferential strain (eCS) <-19% at rest was as accurate as eCS at DSE. In a main study, 123 patients (66% men, age 59 ± 6 years) with relevant coronary stenoses and corresponding severe regional myocardial dysfunction were included and randomized in 2 groups after coronary angiography: group A: intra-procedural myocardial deformation imaging in the cardiac catheter laboratory (CLab), determination of myocardial viability by regional eCS <-19%, in case of positive viability immediate coronary intervention in the same session. Group B: two-step determination of myocardial viability by cardiovascular magnetic resonance (CMR), in case of positive viability coronary intervention. After 18 months follow-up an analysis of the endpoints regarding cardiovascular events, left ventricular (LV) function, and comparison of cost was performed. Group A (N = 61) and group B (N = 62) showed no differences concerning localization of the coronary stenosis, comorbidities, or medical therapy. Cardiovascular events at 18-month follow-up were as follows: group A 13% (N = 10) vs. group B 14% (N = 9, p = 0.288); improvement of LV function: group A: +7 ± 2% vs. group B: +7 ± 3%, p = 0.963; costs: group A: 3096 Dollar vs. group B: 6043 Dollar, p < 0.001. Intra-procedural determination of myocardial viability by myocardial deformation imaging in the CLab is feasible, safe, and cost effective and may become an emerging alternative to the current practice of two-stage viability diagnostics.

OP.4B.01] LEFT VENTRICULAR MECHANICS IN PATIENTS WITH MASKED HYPERTENSION

Objective: We sought to investigate left ventricular (LV) mechanics in subjects with masked hypertension (MH), normotensive and sustained hypertensive patients. Design and method: This cross-sectional study included 209 untreated subjects who underwent 24-hour ambulatory BP monitoring and complete two-dimensional echocardiographic examination (2DE) including multilayer strain analysis. MH was diagnosed if clinic blood pressure (BP) was normal (<140/90 mmHg) and 24-hour BP was increased (> = 130/80 mmHg). Results: According to criteria provided in the Methods, the study sample included 62 normotensive subjects (30%), 64 MH (30%) and 83 sustained hypertensives (40%). 2DE LV longitudinal strain gradually and significantly decreased from normotensive controls across MH individuals to sustained hypertensive patients (−21.3 ± 2.1 vs. −19.1 ± 2 vs. −17.4 ± 1.8 %, p < 0.001). The same is valid for 2DE LV circumferential strain (−21.9 ± 2.9 vs. −20 ± 2.5 vs. −18.4 ± 2.2 %, p < 0.001). 2DE radial strain was not different between groups. 2DE LV longitudinal endocardial and mid-myocardial layer strains progressively decreased from normotensive control to sustained hypertensive individuals (−26.4 ± 4.6 vs. −23.8 ± 3.8 vs. −21 ± 3.6 %, p < 0.001 for endocardial strain; and −21 ± 3.2 vs. −18.8 ± 2.8 vs. −16.8 ± 2.5 %, p < 0.001 for mid-myocardial strain). Similar results were obtained for 2DE LV circumferential endocardial and mid-myocardial layer strains (−28.6 ± 5 vs. −25.4 ± 4.4 vs. −23.2 ± 4 %, p < 0.001 for endocardial strain; and −21.5 ± 2.8 vs. −19.4 ± 2.4 vs. −18.2 ± 2.2 %, p < 0.001 for mid-myocardial strain). Longitudinal and circumferential epicardial layer strains were decreased in sustained hypertensive patients than in normotensive controls. 24-hour systolic BP was associated with peak 2DE LV longitudinal (β = −0.442, p < 0.001), endocardial strain (β = −0.394, p < 0.001), mid-myocardial strain (β = −0.426, p < 0.001) and 2DE circumferential endocardial strain (β = −0.364, p < 0.001) in the whole study population independent of LV mass index and E/e’ ratio. Conclusions: MH significantly influences LV deformation assessed by 2DE traditional strain and 2DE multilayer strain. 24-hour systolic BP is associated with LV deformation evaluated with comprehensive 2DE strain analysis independent of LV structure and diastolic function.

Does masked hypertension impact left ventricular deformation?

Our aim was to compare left ventricular (LV) deformation in subjects with masked hypertension (MH) to normotensive and sustained hypertensive patients. This cross-sectional study included 185 untreated subjects who underwent 24-hour ambulatory blood pressure (BP) monitoring and complete two-dimensional echocardiographic (2DE) examination including multilayer strain analysis. MH was diagnosed if clinic BP was normal (<140/90 mm Hg), and 24-hour BP was increased (≥130/80 mm Hg). 2DE LV longitudinal and circumferential strains gradually and significantly decreased from normotensive controls across MH individuals to sustained hypertensive patients. 2DE radial strain was not different between groups. 2DE longitudinal and circumferential endocardial and midmyocardial layer strains progressively decreased from normotensive control to sustained hypertensive individuals. Longitudinal and circumferential epicardial layer strains were lower in sustained hypertensive patients than in normotensive controls. Clinic and 24-hour systolic BP were associated with 2DE LV longitudinal endocardial strain, midmyocardial strain, and 2DE circumferential endocardial strain in the whole-study population independent of LV structure and diastolic function. MH significantly affect LV deformation assessed by 2DE traditional strain and 2DE multilayer strain. Clinic and 24-hour systolic BP were associated with LV mechanics evaluated with comprehensive 2DE strain analysis independent of LV structure and diastolic function.

Prediction of Outcomes in Patients with Chronic Ischemic Cardiomyopathy by Layer-Specific Strain Echocardiography: A Proof of Concept

Cardiac magnetic resonance imaging (CMR) has been established as a powerful tool for predicting mortality. However, its application is limited by availability and various contraindications. The aim of this study was to evaluate the predictive value of layer-specific myocardial deformation analysis as assessed by strain echocardiography for cardiac events in patients with chronic ischemic left ventricular dysfunction in comparison with CMR. Three hundred ninety patients (mean age, 63±4years; 69% men; mean left ventricular ejection fraction [LVEF], 41±7%) with chronic ischemic cardiomyopathy were prospectively enrolled and underwent strain echocardiography and CMR within 3±1days. LVEF, wall motion score index, and circumferential strain (CS), longitudinal strain, and radial strain for total wall thickness and for three myocardial layers (endocardial, midmyocardial, and epicardial) were determined by echocardiography. The extent of total myocardial scar (TMS) was determined by CMR. Follow-up was obtained for a mean of 4.9±2.2years. Cardiac events were defined as readmission for worsening of heart failure, ventricular arrhythmias, or death of any cause. The incremental value of LVEF, strain parameters, and TMS to relevant clinical variables was determined in nested Cox models. There were 133 cardiac events (34%). Baseline clinical data associated with outcomes were age (hazard ratio [HR], 1.27; P=.04), diabetes mellitus (HR, 1.52; P=.001), and renal insufficiency (HR, 1.77; P=.001) by multivariate analysis. The addition of LVEF, global and endocardial strain parameters, and TMS increased the predictive power, but endocardial CS (HR, 1.52; P<.01) caused the greatest increment in model power (χ(2)=39.2, P<.001). Endocardial CS<-20% was found to be the optimal predictor of prognosis. Endocardial CS is a powerful predictor of cardiac events and appears to be a better parameter than LVEF, TMS by CMR, and other strain variables by echocardiography.

Evaluation of left ventricular transmural mechanics after anthracycline chemotherapy in patients with breast cancer by speckle tracking imaging

Objective To evaluate the left ventricular transmural mechanics changes of breast cancer patients between before and after anthracycline chemotherapy by two-dimensional speckle tracking imaging (2D-STI), and to predict early cardiotoxicity caused by anthracycline. Methods Forty-six breast cancer patients with postoperative anthracycline-based chemotherapy were recruited. Echocardiography were performed on all subjects before and at 1, 3 and 6 anthracycline-based chemotherapeutic cycle. Global longitudinal strain(GLS), endocardial longitudinal strain(LS-endo), epicardial longitudinal strain(LS-epi), global radial strain(GRS), endocardial radial strain(RS-endo), epicardial radial strain(RS-epi), global circumferential strain(GCS), endocardial circumferential strain(CS-endo) and epicardial circumferential strain(CS-epi) were assessed by 2D-STI and transmural myocardial strain gradient-longitudinal strain(TMSG-LS), transmural myocardial strain gradient-radial strain(TMSG-RS), transmural myocardial strain gradient-circumferential strain(TMSG-CS) were calculated. Conventional echocardiographic parameters and strain-related parameters before and after chemotherapy were compared. The receiver operating characteristics(ROC)curve was performed to determine sensitivity and specifity of strain parameters for prediction value of cardiotoxicity induced by anthracycline chemotherapy. Results ①After the sixth cycle of anthracycline chemotherapy, 9 patients (16.4%) had developed anthracycline-induced cardiotoxicity, and 37 patients (80.4%) did not meet the criteria for cardiotoxicity. ②There were no significant differences in conventional echocardiography parameters between before and after chemotherapy (P>0.05). Left ventricular ejection fraction (LVEF), fractional shortening (FS) and E/A significantly decreased, but E/e significantly increased after six cycles of chemotherapy (P LS-endo> GLS> LS-epi. Conclusions After three cycles of chemotherapy, the decreases of TMSG-LS, LS-endo, GLS and LS-epi preceded the change of LVEF and other strain parameters, TMSG-LS and LS-endo can accurately and early detect anthracycline chemotherapy-induced cardiotoxicity. Key words: Echocardiography; Breast neoplasms; Anthracyclines; Transmural myocardial strain gradient; Two-dimensional speckle tracking imaging

Cardiac strain during upright cycle ergometry in adolescent males.

Little evidence exists with regard to changes in cardiac strain that occur during submaximal exercise in young males. The aims of the study were to evaluate the changes that occur in longitudinal (L), radial (R), and endocardial circumferential (EC) strain during submaximal upright cycle ergometry and to examine the test-retest reproducibility of these measurements. Fourteen recreationally active, adolescent (age: 17.9 ± 0.7 years) males volunteered for the study. All subjects underwent an incremental (40 W) submaximal cycle ergometer test. L, R, and EC strain values were obtained using speckle tracking, from two-dimensional B-mode images of the left ventricle (LV) during rest and the initial stages of submaximal exercise (40 and 80 W). The average of 6 LV segments was used to determine both peak wall deformation (%) and the time to peak deformation (ms). There was a statistically (P < 0.05) significant increase from rest to submaximal exercise for peak deformation for L, R, and EC strain. There was a statistically significant (P < 0.05) decrease from rest to submaximal exercise for time to peak for L and R and EC strain and between submaximal workloads for time to peak for L strain and EC strain. Coefficients of variation demonstrated reproducibility for upright strain and strain rate measurements similar to published supine measurements. This study has demonstrated that changes in left ventricular wall deformation (L, R and EC strain) that occur during the transition from rest to submaximal exercise can be reliably measured and confirm that a healthy LV has a hyperdynamic response to exercise.