Three‐Dimensional Global Left Ventricular Myocardial Strain Reduced in All Directions in Subclinical Diabetic Cardiomyopathy: A Systematic Review and Meta‐Analysis

Background Three‐dimensional (3D) speckle tracking echocardiography can identify subclinical diabetic cardiomyopathy without geometric assumption and loss of speckle from out‐of‐plane motions. There is, however, significant heterogeneity among the previous reports. We performed a systematic review and meta‐analysis to compare 3D strain values between adults with asymptomatic, subclinical diabetes mellitus (ie, patients with diabetes mellitus without known clinical manifestations of cardiac disease) and healthy controls. Methods and Results After systematic review of 5 databases, 12 valid studies (544 patients with diabetes mellitus and 489 controls) were eligible for meta‐analysis. Pooled means and mean difference (MD) using a random‐effects model for 3D global longitudinal, circumferential, radial, and area strain were calculated. Patients with diabetes mellitus had an overall 2.31 percentage points lower 3D global longitudinal strain than healthy subjects (16.6%, 95% CI, 15.7–17.6 versus 19.0; 95% CI, 18.2–19.7; MD, −2.31, 95% CI, −2.72 to −2.03). Similarly, 3D global circumferential strain (18.9%; 95% CI, 17.5–20.3 versus 20.5; 95% CI, 18.9–22.1; MD, −1.50; 95% CI, −2.09 to −0.91); 3D global radial strain (44.6%; 95% CI, 40.2–49.1 versus 48.2; 95% CI, 44.7–51.8; MD, −3.47; 95% CI, −4.98 to −1.97), and 3D global area strain (30.5%; 95% CI, 29.2–31.8 versus 32.4; 95% CI, 30.5–34.3; MD, −1.76; 95% CI, −2.74 to −0.78) were also lower in patients with diabetes mellitus. Significant heterogeneity was noted between studies for all strain directions (inconsistency factor [I 2 ], 37%–78%). Meta‐regression in subgroup analysis of studies using the most popular vendor found higher prevalence of hypertension as a significant contributor to worse 3D global longitudinal strain. Higher hemoglobulin A 1c was the most significant contributor to worse 3D global circumferential strain in patients with diabetes mellitus. Conclusions Three‐dimensional myocardial strain was reduced in all directions in asymptomatic diabetic patients. Hypertension and hemoglobin A 1c were associated with worse 3D global longitudinal strain and 3D global circumferential strain, respectively. Registration URL: https://www.crd.york.ac.uk/prospero ; unique identifier: CRD42020197825.

Global Circumferential Strain by Cardiac Magnetic Resonance Tissue Tracking Associated With Ventricular Arrhythmias in Hypertrophic Cardiomyopathy Patients

Background: Hypertrophic cardiomyopathy (HCM) is prone to myocardial heterogeneity and fibrosis, which are the substrates of ventricular arrhythmias (VAs). Cardiac magnetic resonance tissue tracking (CMR-TT) can quantitatively reflect global and regional left ventricular strain from different directions. It is uncertain whether the change of myocardial strain detected by CMR-TT is associated with VAs. The aim of the study is to explore the differential diagnostic value of VAs in HCM by CMR-TT.Materials and Methods: We retrospectively included 93 HCM patients (38 with VAs and 55 without VAs) and 30 healthy cases. Left ventricular function, myocardial strain parameters and percentage of late gadolinium enhancement (%LGE) were evaluated.Results: Global circumferential strain (GCS) and %LGE correlated moderately (r = 0.51, P < 0.001). HCM patients with VAs had lower left ventricular ejection fraction (LVEF), global radial strain (GRS), GCS, and global longitudinal strain (GLS), but increased %LGE compared with those without VAs (P < 0.01 for all). %LGE and GCS were indicators of VAs in HCM patients by multivariate logistic regression analysis. HCM patients with %LGE >5.35% (AUC 0.81, 95% CI 0.70–0.91, P < 0.001) or GCS >-14.73% (AUC 0.79, 95% CI 0.70–0.89, P < 0.001) on CMR more frequently had VAs. %LGE + GCS were able to better identify HCM patients with VAs (AUC 0.87, 95% CI 0.79–0.95, P < 0.001).Conclusion: GCS and %LGE were independent risk indicators of VAs in HCM. GCS is expected to be a good potential predictor in identifying HCM patients with VAs, which may provide important values to improve risk stratification in HCM in clinical practice.

Speckle-Tracking Echocardiography is Preferable Measurement for Detecting the Early and Subtle Alterations of Cardiac Dysfunction in Diabetic Rats

BackgroundMyocardial damage caused by diabetic cardiomyopathy results in cardiac structural and functional abnormalities. Our previous studies have demonstrated that inhibiting RhoA/ROCK signaling pathway improved the structural abnormalities. The early detection of cardiac functional alterations accompanied by structural changes during therapy may facilitate better understanding on the pathophysiologic progress and guiding diabetic cardiomyopathy treatment. This study aimed to identify the optimal diagnostic measures for the early and subtle alterations of cardiac dysfunction in Type 2 diabetes mellitus rats.MethodsTwenty-four male Wistar rats were randomly divided into four groups and treated for 4 weeks: CON (control rats), DM (diabetic rats), DMF (DM + fasudil 10mg/kg/d) and CONF (CON + fasudil 10mg/kg/d). Left ventricular (LV) structure was quantified by histological staining and transmission electron microscopy. LV function and myocardial deformation were performed by high-frequency echocardiography.ResultsMyocardial hypertrophy and fibrosis were increased in diabetic rats and were remarkably alleviated in the DMF group. The diabetic rats had impaired LV performance evidenced by significant reduction of EF, FS and MV E/A, 26%, 34% and 20% respectively, while ROCK inhibition failed to improve the conventional ultrasonic parameters. However, the cardiac time intervals (CTI) parameters and speckle-tracking echocardiography (STE) parameters were significantly improved in the DMF group compared with the DM group (isovolumic contraction time, IVCT: P = 0.029; myocardial performance index, MPI: P = 0.037; fractional area change, FAC: P < 0.001; global circumferential strain, GCS: P = 0.003; global circumferential strain rate, GCSR: P = 0.021). Combining ROC curves with linear regression analysis, STE parameters were characterized by both the optimal predictions for cardiac damage [AUC (95% CI): FAC, 0.927 (0.744 to 0.993); GCS, 0.819 (0.610 to 0.945); GCSR, 0.899 (0.707 to 0.984)] and the strong correlations with cardiac fibrosis (FAC, r = -0.825; GCS, r = 0.772; GCSR, r = 0.829).ConclusionThe results suggest that STE strain and strain rate are preferable indicators of the early detection of subtle alterations in cardiac dysfunction and the quantitation of therapeutic efficacy in diabetic cardiomyopathy.

Comparison between conventional and compressed sensing cine cardiovascular magnetic resonance for feature tracking global circumferential strain assessment

Background Feature tracking (FT) has become an established tool for cardiovascular magnetic resonance (CMR)-based strain analysis. Recently, the compressed sensing (CS) technique has been applied to cine CMR, which has drastically reduced its acquisition time. However, the effects of CS imaging on FT strain analysis need to be carefully studied. This study aimed to investigate the use of CS cine CMR for FT strain analysis compared to conventional cine CMR. Methods Sixty-five patients with different left ventricular (LV) pathologies underwent both retrospective conventional cine CMR and prospective CS cine CMR using a prototype sequence with the comparable temporal and spatial resolution at 3 T. Eight short-axis cine images covering the entire LV were obtained and used for LV volume assessment and FT strain analysis. Prospective CS cine CMR data over 1.5 heartbeats were acquired to capture the complete end-diastolic data between the first and second heartbeats. LV volume assessment and FT strain analysis were performed using a dedicated software (ci42; Circle Cardiovasacular Imaging, Calgary, Canada), and the global circumferential strain (GCS) and GCS rate were calculated from both cine CMR sequences. Results There were no significant differences in the GCS (− 17.1% [− 11.7, − 19.5] vs. − 16.1% [− 11.9, − 19.3; p = 0.508) and GCS rate (− 0.8 [− 0.6, − 1.0] vs. − 0.8 [− 0.7, − 1.0]; p = 0.587) obtained using conventional and CS cine CMR. The GCS obtained using both methods showed excellent agreement (y = 0.99x − 0.24; r = 0.95; p < 0.001). The Bland–Altman analysis revealed that the mean difference in the GCS between the conventional and CS cine CMR was 0.1% with limits of agreement between -2.8% and 3.0%. No significant differences were found in all LV volume assessment between both types of cine CMR. Conclusion CS cine CMR could be used for GCS assessment by CMR-FT as well as conventional cine CMR. This finding further enhances the clinical utility of high-speed CS cine CMR imaging.

Abstract 14245: Fibroblast Growth Factor 23 and Long-term Cardiac Function: The Multi- Ethnic Study of Atherosclerosis

Background: While fibroblast growth factor 23 (FGF23) is associated with incident heart failure (HF) and atrial fibrillation (AF), the mechanisms driving these associations are unclear. FGF23 elevation leads to cardiomyocyte calcium handling abnormalities, suggesting that FGF23 may directly reduce myocardial function. Methods: In the Multi-Ethnic Study of Atherosclerosis, a cohort free of cardiovascular disease at recruitment, we evaluated the associations of serum FGF23 (2000-2002) with measures of left ventricular (LV) and left atrial (LA) mechanical function on cardiac magnetic resonance (CMR) at 10-year follow up (2010-2012). Results: Of 2,276 participants with baseline FGF23 and CMR at 10-year follow up, participants with higher FGF23 levels were more likely white race, taking anti-hypertensive medications, and had lower baseline glomerular filtration rate (GFR). After covariate adjustment, baseline FGF23 levels were independently associated with worse LV global circumferential strain, worse LV mid-wall circumferential strain, and lower LA total emptying fraction in later life ( Table ). The association of FGF23 and LV global circumferential strain was consistent across the spectrum of GFR ( Figure ). While higher FGF23 was associated with higher LV mass (β coefficient per SD higher: 1.14, 95% CI: 0.16, 2.12, P= 0.02), it was not associated with the presence of macroscopic myocardial scar (OR per SD higher: 1.12, 95% CI: 0.86-1.45, P= 0.42). Conclusions: Baseline FGF23 is independently associated with lower LV and LA systolic function in later life. These findings provide mechanistic insight driving the associations of FGF23 with development of both HF and AF.

CMR markers for early right ventricular dysfunction in precapillary pulmonary hypertension

Introduction Precapillary pulmonary hypertension (pPH) causes right ventricular (RV) pressure overload inducing RV remodeling, often resulting in dysfunction and dilatation, heart failure, and ultimately death. The ability of the right ventricle to adequately adapt to increased pressure loading is key for patients' prognosis. RV ejection fraction (RVEF) by cardiac magnetic resonance (CMR) is related to outcome in pPH patients, but this global measurement is not ideal for detecting early changes in RV function. Strain analysis on CMR using feature tracking (FT) software provides a more detailed assessment, and might therefore detect early changes in RV function. Aim 1) To compare RV strain parameters in pPH patients and healthy controls, and 2) to compare strain parameters in a subgroup of pPH patients with preserved RVEF (pRVEF) and healthy controls. Methods In this prospective study, a CMR was performed in pPH patients and healthy controls. Using FT-software on standard cine images, the following RV strain parameters were analyzed: global, septal, and free wall longitudinal strain (GLS, sept-LS, free wall-LS), time to peak strain (TTP, as a % of the whole cardiac cycle), the fractional area change (FAC), global circumferential strain (GCS), global longitudinal and global circumferential strain rate (GLSR and GCSR, respectively). A pRVEF is defined as a RVEF &gt;50%. To compare RV strain parameters in pPH patients to healthy controls, the Mann-Whitney U test was used. Results 33 pPH-patients (55 [45–63] yrs; 10 (30%) male) and 22 healthy controls (40 [36–48] yrs; 15 (68%) male) were included. All RV strain parameters were significantly reduced in pPH patients compared to healthy controls (see table), except for GCS and GCSR. Most importantly, in pPH patients with pRVEF (n=8) GLS (−26.6% [−22.6 to −27.3] vs. −28.1% [−26.2 to −30.6], p=0.04), sept-LS (−21.2% [−19.8 to −23.2] vs. −26.0% [−24.0 to −27.9], p=0.005), and FAC (39% [35–44] vs. 44% [42–47], p=0.02) were still significantly impaired compared to healthy controls. The RV TTP was significantly increased in pPH patients compared to healthy controls (47% [44–57] vs. 40% [33–43], p≤0.001). Conclusions Several CMR-FT strain parameters of the right ventricle are impaired in pPH patients when compared to healthy controls. Moreover, even in pPH patients with a preserved RVEF multiple RV strain parameters (GLS, sept-LS, and FAC) remained significantly impaired, and TTP significantly prolonged, in comparison to healthy controls. This suggests that RV strain parameters may be used as an early marker of RV dysfunction in pPH patients. Funding Acknowledgement Type of funding source: None

Serelaxin Improves Regional Myocardial Function in Experimental Heart Failure: An In Vivo Cardiac Magnetic Resonance Study

Background Animal studies demonstrated that serelaxin lessens fibrosis in heart failure. This study assessed its effect on myocardial deformation using cardiac magnetic resonance and elucidated its relationship to gene regulation and histology in a mouse heart failure model. Methods and Results C57 BL /6J mice were subjected to SHAM (n=4) or transverse aortic constriction ( TAC ). At week 10, TAC mice were randomized to receive either serelaxin (0.5 mg/kg per day; n=11) or vehicle (n=13) for 4 weeks. Cardiac magnetic resonance imaging was performed at baseline and repeated at the end of the study (week 14). Cine images were used to calculate left ventricular ( LV ) global longitudinal, circumferential, and radial strain. Hearts were examined for histology and gene expression. Compared with SHAM , mice 10 weeks after TAC showed increased LV mass with significant decreases in LV deformation parameters, indicating subclinical deterioration of myocardial function. At week 14, TAC mice given serelaxin demonstrated significant improvements in all LV strain parameters and no decrease in LV stroke volume and ejection fraction compared with TAC mice given vehicle. A significant positive correlation between global circumferential strain and the extent of myocardial fibrosis was found, and global circumferential strain correlated significantly with the expression of heart failure genes in serelaxin‐treated mice. Conclusions Serelaxin improved cardiac magnetic resonance–derived myocardial deformation parameters as well as histomorphometric and gene expression findings in mice with heart failure. Cardiac magnetic resonance–derived myocardial mechanics correlate with histology and gene expression, stressing its utilization in myocardial remodeling.

P307 Trajectories of Myocardial Strain Across the Spectrum of Aortic Stenosis

Introduction Optimal timing of intervention in aortic stenosis (AS) is key. Left ventricular deformation parameters are sensitive markers of myocardial wellbeing in AS, but data is sparse so strain does not currently feature in the clinical decision-making process governing timing of AS intervention. We explore the trajectory of myocardial strain in AS of varying severity to potentially identify the most sensitive periods for valve intervention. Methods 50 patients from across the spectrum of isolated AS were prospectively recruited: mild AS n = 10; moderate AS n = 10; and severe AS n = 30 of which n = 10 in each of 3 ejection fraction (EF) groups: EF &gt; 50%, EF = 40-49% and EF &lt; 35%. Longitudinal, circumferential, and radial strain were measured by speckle tracking echocardiography (STE) using TomTec software. Results Strain parameters and EF were not significantly different between mild and moderate AS groups but almost all parameters (except for global circumferential strain (GCS)) showed significant deterioration with progression to severe AS, even in spite of preserved EF (&gt;50%; Table1). In patients with severe AS, strain parameters showed no significant differences between hearts with EF &gt; 50% and EF 40-49%, but they continued to deteriorate significantly (p &lt; 0.05) as hearts transitioned from 40-49% to &lt;35% (Figure 1, a&b). Conclusion The heart can maintain its deformation and global systolic function throughout mild and moderate AS but strain deteriorates significantly in severe AS, irrespective of EF. Tracking the precise timings of strain deterioration in severe AS could help refine optimal timings of AS intervention. LVEF and strain in varying AS severity Left ventricle ejection fraction and strain values in varying severity of AS Mild (n = 10) Moderate (n = 10) Severe (n = 10) P-value Mean (SD) Mean (SD) Mean (SD) EF (%) 65.4 (6.1) 65.8 (9.0) 60.4 (3.6)*§ 0.15 GLS (%) -14.2 (2.1) -13.6 (2.3) -11.8 (2.9)* 0.09 GCS (%) -30.3 (9.1) -31.0 (11.4) -26.5 (8.2) 0.55 GRS (%) 55.9 (15.5) 52.6 (24.0) 35.9 (13.5)*§ 0.05 EF: ejection fraction; GLS: global longitudinal strain; GCS: global circumferential strain; GRS: global radial strain; SD: standard deviation. Severe (n = 10): Severe AS with preserved EF &gt;50%. P-value: ANOVA-single factor; comparison in-between groups was performed using unpaired t-test (parametric) and Mann Whitney test (non-parametric). *significant difference P &lt; 0.05 mild vs severe. §significant difference P &lt; 0.05 moderate vs severe. Abstract P307 Figure.