Diastolic wall strain: a simple marker of abnormal cardiac mechanics

Cardiovascular Ultrasound Diastolic wall strain: a simple marker of abnormal cardiac mechanics Senthil Selvaraj 0 Frank G Aguilar 0 Eva E Martinez 0 Lauren Beussink 0 Kwang-Youn A Kim 2 Jie Peng 2 Daniel C Lee 0 Ateet Patel 0 Jin Sha 1 Marguerite R Irvin 1 Donna K Arnett 1 Sanjiv J Shah 0 0 Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine , 676 N. St. Clair St., Suite 600, Chicago, IL 60611 , USA 1 Departments of Epidemiology and Biostatistics, School of Public Health, University of Alabama Birmingham , Birmingham, AL , USA 2 Department of Preventive Medicine/Biostatics, Northwestern University Feinberg School of Medicine , Chicago, IL , USA Background: Diastolic wall strain (DWS), defined using posterior wall thickness (PWT) measurements from standard echocardiographic images (DWS = [PWT(systole)-PWT(diastole)]/PWT(systole)), has been proposed as a marker of left ventricular (LV) diastolic stiffness. However, the equation for DWS is closely related to systolic radial strain, and whether DWS is associated with abnormal cardiac mechanics (reduced systolic strains and diastolic tissue velocities) is unknown. We sought to determine the relationship between DWS and systolic and diastolic cardiac mechanics. Methods: We calculated DWS and performed speckle-tracking analysis in a large population- and family-based study (Hypertension Genetic Epidemiology Network [HyperGEN]; N = 1907 after excluding patients with ejection fraction [EF] < 50% or posterior wall motion abnormalities). We measured global longitudinal, circumferential, and radial strain (GLS, GCS, and GRS, respectively) and early diastolic (e') tissue velocities, and we determined the independent association of DWS with cardiac mechanics using linear mixed effects models to account for relatedness among study participants. We also prospectively performed receiver-operating characteristic (ROC) analysis of DWS for the detection of abnormal cardiac mechanics in a separate, prospective validation study (N = 35). Results: In HyperGEN (age 51 14 years, 59% female, 45% African-American, 57% hypertensive), mean DWS was 0.38 0.05. DWS decreased with increasing comorbidity burden (-coefficient 0.013 [95% CI 0.015, 0.011]; P < 0.0001). DWS was independently associated with GLS, GCS, GRS, and e' velocity (adjusted P < 0.05) but not LV chamber compliance (EDV20, P = 0.97). On prospective speckle-tracking analysis, DWS correlated well with GLS, GCS, and GRS (R = 0.61, 0.57, and 0.73, respectively; P < 0.001 for all comparisons). C-statistics for DWS as a diagnostic test for abnormal GLS, GCS, and GRS were: 0.78, 0.79, and 0.84, respectively. Conclusions: DWS, a simple parameter than can be calculated from routine 2D echocardiography, is closely associated with systolic strain parameters and early diastolic (e') tissue velocities but not LV chamber compliance. Strain; Speckle-tracking; Echocardiography; Cardiac mechanics; Diastolic dysfunction; Systolic dysfunction - Background Left ventricular (LV) diastolic dysfunction is common in the general population, and is associated with incident heart failure and increased mortality [1,2]. The pathophysiology of diastolic dysfunction is complex, but can be simply described as impaired LV myocardial relaxation and/or increased LV stiffness, both of which can lead to increased LV filling pressures at rest or with exercise. Although Doppler echocardiography is able to detect impaired LV relaxation and elevated LV filling pressures quite well, the detection of reduced LV compliance (i.e., increased LV stiffness) has proven to be more difficult, requiring invasive pressure-volume analysis for calculation of the end-diastolic pressure-volume relationship (EDPVR). Recently, a non-invasive, load-independent, and reproducible estimator of LV stiffness using 2-dimensional (2D) echocardiography, namely diastolic wall strain (DWS), has been proposed [3,4]. DWS, an extension of linear elastic theory, uses the difference between posterior wall thickness in systole (PWTs) and diastole (PWTd) to approximate LV stiffness [4]. According to the theory, decreased wall thinning during diastole reflects reduced LV compliance and distensibility, and thus, increased LV stiffness. However, DWS, as it name implies, is closely related to systolic strain. DWS, calculated as [(PWTs) (PWTd)]/ (PWTs), can be simplified purely in terms of myocardial (wall) strain, defined as [(PWTs) (PWTd)]/(PWTd). By rearranging the two equations, DWS can be expressed as [(wall strain)/(1 + wall strain)] [4]. Takeda et al., whose work validated the use of DWS, failed to demonstrate a correlation between tissue-Doppler derived strain and DWS [4]. However, speckle-tracking echocardiography holds several advantages over tissue-Doppler in measuring strain, including superior reliability, less angle dependence, and greater ability to differentiate normal from dysfunctional myocardial segments [5]. Though Takeda et al. demonstrated that DWS correlates moderately well (R = 0.47, P < 0.05) with invasive measurements of myocardial stiffness [4], uncertainty still remains in how best to interpret this new marker. A recent editorial has framed the debate [6]. DWS can conversely be thought of as an index of wall thickening, not just wall thinning, and may therefore measure LV systolic function. Further, DWS should theoretically correlate well with radial strain, which is itself a systolic index. That DWS may actually correlate well with both systolic and diastolic indices suggests, in fact, that DWS is rather an overall marker of myocardial health and performance. The evaluation of echocardiograms from the Hypertension Genetic Epidemiology Network (HyperGEN) study permits a robust assessment of the relationship between DWS and cardiac mechanics. HyperGEN, conducted from 19962002, originally sought to determine the genetic basis for familial hypertension. Advantages of the HyperGEN study include a bi-racial sample of approximately 3600 participants, comprehensive clinical and laboratory data collection, and 2D/Doppler echocardiographic data [7]. Though echocardiograms were performed at a time prior to digital storage, we have successfully implemented a technique to convert analog echocardiograms to digital format, permitting post-hoc speckle-tracking with the subsequent determination of cardiac mechanics [8]. Therefore, we sought to determine the association of DWS with LV systolic and diastolic mechanics. We hypothesized that DWS correlates with both systolic and diastolic measures of LV performance. We further hypothesized that reduced DWS is associated with systolic LV mechanics (i.e., decreased LV strain), even when adjusting for LV geometry and echocardiographic indices of filling pressures and myocardial relaxation. Methods Study population HyperGEN, part of the National Institutes of Health Family Blood Pressure Program (FBPP), is a cross sectionalstudy consisting of five U (...truncated)