Diastolic Cardiac Function by MRI—Imaging Capabilities and Clinical Applications

Most cardiac studies focus on evaluating left ventricular (LV) systolic function. However, the assessment of diastolic cardiac function is becoming more appreciated, especially with the increasing prevalence of pathologies associated with diastolic dysfunction like heart failure with preserved ejection fraction (HFpEF). Diastolic dysfunction is an indication of abnormal mechanical properties of the myocardium, characterized by slow or delayed myocardial relaxation, abnormal LV distensibility, and/or impaired LV filling. Diastolic dysfunction has been shown to be associated with age and other cardiovascular risk factors such as hypertension and diabetes mellitus. In this context, cardiac magnetic resonance imaging (MRI) has the capability for differentiating between normal and abnormal myocardial relaxation patterns, and therefore offers the prospect of early detection of diastolic dysfunction. Although diastolic cardiac function can be assessed from the ratio between early and atrial filling peaks (E/A ratio), measuring different parameters of heart contractility during diastole allows for evaluating spatial and temporal patterns of cardiac function with the potential for illustrating subtle changes related to age, gender, or other differences among different patient populations. In this article, we review different MRI techniques for evaluating diastolic function along with clinical applications and findings in different heart diseases.

Repurposing glycated hemoglobin as a possible marker of myocardial ageing in asymptomatic older adults

Background The adverse consequences of diabetes mellitus on cardiovascular health is well-established. However, few studies have studied the impact of diabetes on ageing. In our previous investigations, we identified distinct patterns of myocardial ageing among older adults otherwise asymptomatic for clinical cardiovascular disease. In this analysis, we hypothesize that glycated hemoglobin (HbA1c) may be differentially associated with these distinct signatures of myocardial ageing, thereby providing greater precision towards future preventative trials. Methods We performed extensive cardiovascular examinations on a cohort of asymptomatic aged community adults. Transthoracic echocardiography measured left ventricular structure and function. LV filling pressure was measured as the ratio between early mitral inflow velocity and mitral annular early diastolic velocity. Longitudinal left atrial (LA) strain comprising reservoir strain (ɛs), conduit strain (ɛe) and booster strain (ɛa) and their corresponding peak strain rates (SRs, SRe, SRa) were measured using cardiac magnetic resonance (CMR) feature tracking technique. Blood sampling for biomarkers were performed simultaneously with cardiovascular examinations. Results Among n=515 community adults in sinus rhythm and without cardiovascular disease [mean age 73±4 years, 255 (50%) females], 116 (23%) had diabetes. Age (73 vs 73 years) and heart rate (72 vs 75 beats per minute) were similar between diabetic and non-diabetic older adults. Diabetic older adults are mostly male (59% vs 48%, p=0.046), had larger body mass indices (24 vs 23 kg/m2, p=0.027), and greater burdens of hypertension (81% vs 41%, p<0.0001) and dyslipidemia (79% vs 43%, p<0.0001), compared to non-diabetic older adults. Diabetics had worse LV myocardial relaxation [(ratio of peak velocity flow in early diastole E (m/s) to peak velocity flow in late diastole by atrial contraction A (m/s), 0.8±0.2 vs 0.9±0.3, p=0.031), worse LV filling pressures (10.9±3.1 vs 10.1±3.3, p=0.022), reductions in LA global strain (−33±17 vs −28±9.7, p=0.016), LA conduit strain ɛe (12±4.3 vs 14±4.1, p=0.045), increases in SRe (−1.2±0.4 vs −1.3±0.5, p=0.042) and reductions in SRe: SRa ratio (0.5±0.2 vs 0.7±0.3, p=0.0059) compared to non-diabetics. Based on multivariate analysis, HbA1c was independently associated with LV myocardial relaxation (β=−0.08 (−0.1, −0.03), p=0.002), LA conduit strain (β=−0.9, (−1.6, −0.1), p=0.025), LA conduit strain rate (β=0.1, (0.04, 0.2), p=0.005), strongly associated with LA global strain (β=3.0, (0.9, 5.1), p=0.006), but not associated with LV filling pressure (β=0.5 (−0.04, 1.0), p=NS). Conclusion Our detailed examinations revealed distinct associations between glycated hemoglobin and myocardial functions that additionally varied in magnitude. As a contemporary biomarker, glycated hemoglobin may be useful for stratifying risks associated with myocardial ageing, particularly in ageing-related left atrial myopathies. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): National Medical Research Council of Singapore; Singhealth Foundation

Abstract 448: Strain Rate Dependent Myosin Head Position Changes During Relaxation

Impaired cardiac relaxation is present in nearly all cases of heart failure and possibly in up to 25% of the asymptomatic population. Myocardial relaxation is known to be biochemically modified by the calcium reuptake rate, thin filament calcium sensitivity, and crossbridge kinetics. Mechanical regulation of relaxation was thought to be regulated via afterload, but we have recently shown that a lengthening strain was sufficient to modify relaxation. Further, the relaxation rate is actually dependent on the strain rate, a relationship that we termed Mechanical Control of Relaxation. Computational modeling suggests that myosin detachment is a key mechanism underlying Mechanical Control of Regulation, but to date, no experimental evidence for this was available. The objective of this study was to determine if myosin head position changed in response to lengthening strains during relaxation. Intact cardiac trabeculae were mounted within the beamline of the Biophysical Collaborative Access Team (BioCAT) beamline at the Advanced Photon Source at Argonne National Laboratories. The trabeculae were paced and load-clamps were performed during time-resolved imaging of the equatorial axis, which primarily reflects myosin head positioning. Activation (pacing) caused the myosin head localization to shift from the thick filament to near the thin filament (increased I 1,1 /I 1,0 ratio). During stretch, there was a transient decline of the I 1,1 /I 1,0 ratio which recovered until relaxation was complete, when the ratio again reduced indicating myosin returned to the thick filament. These preliminary data suggest that Mechanical Control of Relaxation is caused by perturbations in myosin, but the late-diastolic kinetics suggests that the strain-rate dependent detachment does not lead to immediate deactivation of myosin heads. Modifications of myosin ATPase properties may reveal more specific regulatory targets, which may provide new insight and targets for treating impaired myocardial relaxation.

Why Myocardial Relaxation Always Slows at Cardiac Pathology?

Chronic heart failure (CHF) in most cases is due to a decrease in myocardial contractility. In particular, this results in a reduction in the maximum rate of the pressure development in the left ventricle. At the same time the maximal rate of pressure fall at relaxation is also reduced. This is not surprising, since both depend on Ca ++ myoplasmic concentration. But most of cardiac pathologies have been associated with the impairement of myocardial relaxation to a greater extent than the contraction. In the review a new view has been proposed according to which this phenomenon is attributable to restructuring of titin, the sarcomeric protein that connects the ends of myosin filaments with the sarcomeric board, lines Z. A spring-like molecule of titin shrinks at sarcomeric contraction and straightens in parallel with removing of Ca ++ from myofibrils. A reduction of its stiffness, facilitating the filling of the left ventricle, can reduce restoring force of titin and thereby slow relaxation. The survey provides information about the functions of the calcium transport system and titin in the normal heart and in CHF observed both in experimental models and in patients.

P2437Screening for cardiac relaxation abnormalities using surface ECG wavelets for identifying high-risk cardiac phenotypic abnormalities

Background The impairment of myocardial relaxation is a strong predictor of all-cause mortality and has been proposed to be a potential tool for cardiovascular (CV) risk stratification. We investigated a novel signal-processed electrocardiography (spECG) technique to extract the features of abnormal myocardial relaxation as a screening tool to identify high-risk CV patients. Methods Time–frequency-energy features extracted from continuous wavelet-transformed spECG (Fig. A) were obtained in 1,006 cases. A machine learning model was trained for predicting abnormal myocardial relaxation as a screening tool for detecting high-risk CV patients. High-risk CV phenotype was defined as presence of LV hypertrophy, advanced LV diastolic dysfunction (grade 2 or 3), LV ejection fraction <50%, and/or significant valvular heart disease. Results After training with 5-fold cross validation using data from 810 patients, the machine learning model when tested in an independent hold-out validation set of 180 cases, showed an area under receiver-operating characteristic curve (AUC) of 0.83 (p<0.001) for prediction of myocardial relaxation impairment (Fig. B). A prediction of abnormal relaxation was associated with older patients (64±11 vs. 45±16 years old, p<0.001) with a higher prevalence of coronary artery disease (23% vs. 7%, p=0.004), hypertension (70% vs. 40%, p<0.001), and diabetes (30% vs. 9%, p=0.001). Furthermore, a prediction of abnormal myocardial relaxation was associated with increased likelihood of high-risk CV phenotypes (Odds ratio: 3.93, p<0.001) including LV hypertrophy (Odds ratio: 2.62, p=0.028), advanced LV diastolic dysfunction (Odds ratio: 11.4, p=0.020), and LV ejection fraction <50% (Odds ratio 10.5, p=0.025). Age and gender modified the prediction of abnormal relaxation with higher diagnostic value seen for patients under 60 years (Fig C, AUC: 0.88, p<0.001) and in male patients (Fig D, AUC: 0.87, p<0.001). The algorithm for abnormal relaxation also showed robust prediction of LV ejection fraction <50% (Fig E, AUC: 0.91, p<0.001) in male patients. spECG showed significant net reclassification improvement (0.47, p<0.001) and integrated discrimination improvement (0.16, p<0.001) over traditional surface ECG interpretation using Glasgow score for predicting abnormal relaxation and other high-risk phenotypic presentations. ROC curves Conclusion The spECG provided a robust prediction of abnormal myocardial relaxation and may be a valuable screening strategy for early detection of high-risk cardiac structural and functional abnormalities.