Prognostic Value of Left and right ventricular deformation strain analysis on Acute Cellular rejection in Heart Transplant recipients: A 6-year outcome study.

PURPOSE: Two-dimensional (2D) strain analysis is a sensitive method for detecting myocardial dysfunction in acute cellular rejection (ACR) from post-transplant complications. This study aims to evaluate the utility of novel left (LV) and right ventricular (RV) strain parameters for prognostic risk stratification associated with ACR burden at 1-year post transplantation. METHODS: 128 Heart transplant patients, assessed between 2012 and 2018, underwent transthoracic echocardiography and endomyocardial biopsy. 2D strain analysis was performed and history of rejection burden was assessed and grouped according to ACR burden at 1-year post transplantation. The primary endpoint was all-cause mortality at 6-years follow up. RESULTS: 21 patients met primary the endpoint. Multivariate analysis of 6-year all-cause mortality showed LV global longitudinal strain (LV GLS) (Hazard Ratio [HR] = 1.21, CI = 1.06-1.49), LV early diastolic strain rate (LV ESr) (HR = 1.31, CI = 1.12-1.54), RV GLS (HR = 1.12, CI = 1.02-1.25) and RV ESr (HR = 1.26, CI = 1.12-1.47) were significant predictors of outcome. Univariate analysis also showed LV GLS, LV ESr, RV GLS and RV ESr were significant predictors of outcome. Optimal cut-off for predicting 6-year mortality for LV GLS by receive operator characteristic was 15.5% (sensitivity: 92%, specificity: 79%). Significant reductions (p < 0.05) in LV GLS, RV GLS and LV and RV ESr between rejection groups were seen. CONCLUSIONS: Non-invasive LV and RV strain parameters are predictors of mortality in post-transplant patient with ACR. LV GLS and LV ESr are superior to other strain and conventional echo parameters.

Novel left and right ventricular strain analysis to detect subclinical myocardial dysfunction in cardiac allograft rejection.

Early detection of acute cellular rejection (ACR) by echocardiography shows potential clinical benefit as ACR remains a significant contributor to morbidity and mortality. This retrospective, longitudinal study sought to investigate the use of novel left (LV) and right ventricular (RV) strain analysis to detect biopsy proven ACR. 46 heart transplant patients (Mean age 46 ± 16 years) with biopsy proven ACR were grouped according to biopsy results: 1R-ACR (n = 36) and 2R-ACR (n = 10). Serial two-dimensional transthoracic echocardiography with strain analysis was performed. Echocardiographic parameters were serially measured: (1) rejection free period (0R-ACR); (2) pre-ACR period (pre-ACR); (3) during ACR (1R-ACR or 2R-ACR) and (4) post-ACR (Post-ACR). Significant reductions for LV Global Longitudinal Strain (LV GLS) and LV Early diastolic Strain rate (LV ESr) were observed between 0R-ACR and pre-ACR (LV GLS 0R-ACR: 17.3% vs Pre-2R ACR: 15.4%, p = 0.016; LV ESr 0R-ACR: 1.00/s vs Pre-2R ACR: 0.74/s, p = 0.007) with LV ESr demonstrating the highest sensitivity (92%) and specificity (81%) to predict ACR. LV ESr and the E/LV ESr ratio were significantly different (p = 0.0001; p = 0.016) during pre-1R ACR period vs 0R whereas LV GLS showed no significant differences for grade 1R-ACR. Diastolic mechanical dispersion showed significant increases in dispersion during ACR for the 1R-ACR group and early significant increases pre-2R ACR. Systolic and diastolic RV strain parameters showed a similar trend for both ACR groups. Systolic and diastolic strain parameters can detect myocardial dysfunction before biopsy confirmed 2R-ACR. Early diastolic strain rate parameters are most sensitive detecting subclinical myocardial dysfunction pre-ACR. Novel strain parameters are potentially useful clinical tool for prediction of early ACR in heart transplant.

Myocardial work and left ventricular contractile reserve during stress echocardiography: An angiographic validation.

OBJECTIVE: This study sought to determine the contractile reserve (CR) response to exercise stress echocardiography (ESE) quantified by the novel parameter, non-invasive myocardial work (MW), in subjects with angiographically proven coronary artery disease (CAD). METHODS: CR was measured by the relative change in ejection fraction (EF), global longitudinal strain (GLS) and MW indices from rest to peak exercise in 304 patients referred for clinically indicated ESE. Positive ESE patients proceeded to coronary angiography and further risk stratified based on either percutaneous or surgical intervention. RESULTS: CRGLS and global work index (CRGWI ) significantly decreased with exercise induced ischemia and angiographically proven significant CAD (CRGLS -1.6±3.5%; CRGWI -8.6±511 mm Hg% decrement, p < 0.001) compared to non-ischemic patients (CRGLS 1.4±2.2%; CRGWI 398±404 mm Hg% improvement). Global constructive work (CRGCW ) was significantly higher (p < 0.0001) in non-ischemic (818±457 mm Hg%) and blunted in ischemic patients (208±550 mm Hg%). CRGCW (AUC .81; 95%CI:.75-.86) demonstrated the most association for inducible ischemia followed by CRGLS (AUC .75; 95%CI:.69-.80), CRGWI (AUC .73, 95%CI:.67-.79) and CREF (AUC .71; 95%CI:.65-.77, p < 0.001). Subgroup analysis showed patients requiring surgical revascularization demonstrated a significantly lower CRGWE (-11.5±7.6%, p < 0.05) as a result of reduced CRGCW (281±573 mm Hg%, p < 0.05) and increased global wasted work (CRGWW , 289±151 mm Hg%, p = 0.09). CONCLUSION: Multivessel disease requiring surgical revascularization have the greatest reduction in CR. MW may potentially improve detection of ischemia and further risk stratification during ESE to maximize the benefits of revascularization.

Resting global myocardial work can improve interpretation of exercise stress echocardiography.

Sensitivity and specificity of ESE to determine hemodynamically significant coronary artery disease (CAD) is limited by subjective qualitative interpretation resulting in false-positive results. The objective of this study was to determine whether resting myocardial work estimated from non-invasive left ventricular pressure-strain loops can help improve the interpretation of exercise stress echocardiography (ESE). Resting global myocardial work was performed on 288 patients referred for clinically indicated ESE with no resting regional wall motion abnormalities and normal ejection fraction (≥ 55%). Coronary angiography was used to validate the presence of significant CAD in those with a positive ESE. Resting global myocardial work index (GWI) was significantly reduced (p < 0.001) in patients with true-positive (1544 ± 354 mmHg%) compared to negative (1819 ± 317 mmHg%) and false-positive (1857 ± 344 mmHg%) ESE. A GWI of ≤ 1391 mmHg (AUC 0.73; sensitivity 94%; specificity 73%) predicted true-positive ESE. Predictors of a true-positive ESE were (1) lower myocardial work efficiency (odds ratio 0.731, 95% CI 0.58-0.92, p = 0.007), (2) lower GWI (odds ratio 0.997, 95% CI 0.996-0.999, p = 0.006) (3) male gender (odds ratio 5.47, 95% CI 1.84-16.31, p = 0.002) and (4) E/e' ratio (odds ratio 1.15, CI 1.01-1.31, p = 0.032). Myocardial work is a potentially valuable quantitative parameter that provides incremental value over qualitative ESE interpretation and improves appropriate patient selection for coronary angiography.

Global Myocardial Work Is Superior to Global Longitudinal Strain to Predict Significant Coronary Artery Disease in Patients With Normal Left Ventricular Function and Wall Motion.

BACKGROUND: Noninvasive detection of functionally significant coronary artery disease (CAD) by echocardiography remains challenging, with the need to perform stress imaging to detect ischemia. The aim of this study was to determine whether global myocardial work (MW), derived from noninvasive left ventricular (LV) pressure-strain loops at rest, can predict significant CAD in patients without regional wall motion abnormalities and preserved LV ejection fraction (EF). METHODS: One hundred and fifteen patients referred for coronary angiography who had EF ≥ 55%, no resting regional wall motion abnormalities, and no chest pain were assessed using echocardiography. Global MW was derived from noninvasive LV pressure-strain loops constructed from speckle-tracking echocardiography indexed to brachial systolic blood pressure. Global constructive work represented the sum of positive work due to myocardial shortening during systole and negative work due to lengthening during isovolumic relaxation. Global wasted work represented energy loss by myocardial lengthening in systole and shortening in isovolumic relaxation. Global MW efficiency was derived from the percentage ratio of constructive work to the sum of constructive work and wasted work. RESULTS: Patients with significant CAD demonstrated a significantly reduced global MW (P < .001) compared with those without CAD. Global longitudinal strain was significantly reduced (P < .001) in patients with multivessel CAD but not those with single-vessel CAD (P = .47). Receiver operating characteristic curve analysis demonstrated that global MW was the most powerful predictor of significant CAD (area under the curve = 0.786) and was superior to global longitudinal strain (area under the curve = 0.693). The optimal cutoff global MW value to predict significant CAD was 1,810 mm Hg% (sensitivity, 92%; specificity, 51%). CONCLUSIONS: Noninvasive global MW derived using LV pressure-strain loops at rest is a more sensitive index than global longitudinal strain to detect significant CAD in patients with no regional wall motion abnormalities and normal EF. This is a potential valuable clinical tool to assist in the early diagnosis of CAD.

A new approach to assess myocardial work by non-invasive left ventricular pressure-strain relations in hypertension and dilated cardiomyopathy.

Aims: Non-invasive left ventricular (LV) pressure-strain loop (PSL) provides a novel method of quantifying myocardial work (MW) with potential advantages over conventional global longitudinal strain (GLS) by incorporating measurements of myocardial deformation and LV pressure. We investigated different patterns of LV PSL and global MW index (GWI) in patients with hypertension (HTN) and dilated cardiomyopathy (CMP). Methods and results: Seventy-four patients underwent transthoracic echocardiography and strain analysis before coronary angiography. Patients were divided into three groups: control, HTN, and CMP. GWI was calculated as the area of the LV PSL as a product of strain × systolic blood pressure. MW efficiency (GWE) is derived from the percentage ratio of constructive work (GCW) to sum of constructive work (GCW) and wasted work (GWW). Influences of HTN and LV function on its relationship with MW were evaluated. GLS and LV ejection fraction were preserved in the HTN group with no difference from controls. GWI was significantly higher in moderate to severe HTN patients (P = 0.004) as a compensatory mechanism to preserve LV contractility and function against an increase in afterload. GWE was preserved in HTN patients due to the proportional increase in GCW and GWW. GLS, GWI, and GWE were significantly reduced in CMP (P < 0.05), with a trend in rightward shift and reduction in the LV PSL. Conclusion: GWI is a potential new technique that allows better understanding of the relationship between LV remodelling and increased wall stress under different loading conditions.