Quantifying longitudinal right ventricular dysfunction in patients with old myocardial infarction by using speckle-tracking strain echocardiography

We retrospectively reviewed the consecutive echocardiographic data between July 2005 and January 2009, and selected 71 patients with OMI (the OMI group: 67 ± 11 years) who underwent complete echocardiography including optimal RV-focused apical four-chamber images using Vivid 7 among various echocardiography ultrasound systems in our echo laboratory at Mie University Hospital, which were available for off-line analysis (GE-Vingmed Ultrasound AS, Horten, Norway). All patients had experienced MI for over 1month and were diagnosed with reference to their personal history, physical examinations, laboratory tests, electrocardiography, echocardiography, coronary angiography, and cardiac magnetic resonance imaging. Patients were excluded from the study if they had suboptimal images, atrial fibrillation, significant primary valvular heart disease, prosthetic valves, or a pacer wire in the right ventricle. To minimize the influence of confounding factors in the evaluation of RV function after MI in the LV myocardium, patients with a coexisting RV infarction were excluded in the present study. Patients who had been diagnosed with non-ischemic dilated cardiomyopathy before the onset of MI were also excluded in the present study. The diagnosis of RV infarction was defined by ST segment elevation >0.1 mV in lead V4R in the 12-lead electrocardiography examination. Non-existence of obvious RV infarction was confirmed by using cardiac MRI and coronary angiography in patients with silent OMI who did not undergo 12-lead electrocardiography examination at the onset of MI. We also studied 45 age-matched and gender-matched normal subjects (the Control group: 66 ± 11 years) who had no history of cardiopulmonary disease, and who had normal electrocardiographic results and normal echocardiographic results. The protocol was approved for use by the Human Studies Subcommittee of Mie University’s Graduate School of Medicine.

Arm-cuff blood pressure measurements were performed at the beginning of the echocardiographic study for all subjects [6]. Interventricular septal and LV posterior wall thickness, LV end-diastolic dimension, end-systolic dimension, and fractional shortening were assessed from the parasternal long axis view. LV volume indices and ejection fraction were assessed using biplane Simpson’s rule. LV mass index was calculated on the basis of the area-length method [6]. The Doppler-derived stroke volume was normalized by body surface area. Ratio of peak early to late diastolic transmitral flow velocity (mitral E/A) and the deceleration time (DT) of E velocity was calculated using pulsed Doppler echocardiography [6, 7]. Averaged peak early diastolic mitral annular velocity (Ea) at the inferior-septal and LV lateral site was used as a marker of LV diastolic function. The E/Ea ratio was calculated as a Doppler parameter reflecting LV filling pressure [8]. The RV end-diastolic area (EDA) index, the end-systolic area (ESA) index, and the fractional area change (FAC) from the apical 4-chamber view were also measured [5]. Tricuspid annular plane systolic excursion (TAPSE) was measured for assessing longitudinal RV systolic function [9]. The RV myocardial performance index (MPI) was calculated as the sum of the isovolumic contraction time and isovolumic relaxation time divided by the ejection time [5, 9, 10]. Estimated peak systolic pulmonary artery pressure was calculated from the sum of the maximal pressure difference between the right ventricle and the right atrium, as calculated by the continuous-wave Doppler flow velocity, and the mean right atrial pressure, as estimated by the diameter of the inferior vena cava and its respiratory variation [9]. Pulmonary vascular resistance (PVR) was noninvasively estimated using echocardiography [11]. All echocardiographic measurements represent the average of 3 beats. Blood test including measurement of plasma brain natriuretic peptide (BNP) levels was performed within the 2 weeks prior to or after the echocardiography examination.

Speckle-tracking analysis was used to generate regional and global myocardial strain in both the left and right ventricles (Figure 1). Longitudinal LV strain was assessed in the apical 4-chamber, 2-chamber, and long axis views, and radial and circumferential LV strains were assessed in the parasternal short-axis views at the mid-LV level. Longitudinal RV strain was assessed in the apical 4-chamber view [12]. Average frame rate for the analysis was 64 ± 9 Hz. For speckle-tracking echocardiography assessment, routine B-mode gray scale images were analyzed using commercially available software (EchoPAC, GE Vingmed, Horton, Norway). Myocardial strain is expressed as the percent change from the original dimension at end-diastole, and myocardial thickening or lengthening was represented as a positive value, while myocardial thinning or shortening was represented as a negative value [5, 6]. The software automatically divided into 6 standard segments in the LV apical 4-chamber, 2-chamber, long-axis, mid-LV short-axis, and RV apical 4-chamber views, respectively (Figure 1). Peak systolic strain (PSS) obtained from time-strain curves were defined as the indices of myocardial systolic contraction. Global RV PSS in the 6 segments was assessed, and the free wall RV PSS was obtained by averaging 3-site strain signals simultaneously (the basal RV lateral wall, the mid RV lateral wall, and the apical RV wall). Global LV radial PSS was obtained by averaging 6-site strain signals simultaneously [13].

After echocardiography assessments, patients were followed for 4.7 ± 2.3 years (median 5.3 years). The study end-point was heart failure hospitalization or cardiovascular death. The causes of death were determined by the attending doctors blinded to the group assignment.

There were a total of 99 culprit territory vessels. Forty-six patients (65%) had one infarcted segment within a territory of the left anterior descending artery (n = 29), the left circumflex artery (n = 8), or the right coronary artery (n = 9), and 25 patients (35%) had more than one infarcted segments. The time interval from the first onset of MI was <1 year in 28% of patients, ≥1 year (range 1–35 years) in 39% of patients, and was unknown in 32% of patients mainly because of silent MI. Successful primary revascularization early in the course of AMI was achieved only in 27 patients and 27% of the all culprit coronary lesions responsible for MI, mainly due to high prevalence of patients with silent ischemia with multivessel disease. There were 26 vessels with residual total occlusion in the culprit lesion responsible for MI. Table 1 shows the clinical characteristics of the study groups. There were no statistical differences in height, body mass index, blood pressure, and heart rate between the Control and OMI group. Estimated glomerular filtration rate [14] was lower in the OMI group compared to the Control group. Plasma BNP levels were varied from 2 to 3000 pg/ml with median value of 162 pg/ml in the OMI group.

Table 2 shows the left-sided echocardiographic data of the study subjects. The OMI group had thickened LV wall, large LV chamber size, greater LV mass index, and reduced LV ejection fraction compared with the Control group, indicating dilatational LV remodeling in patients with OMI. Although mitral E/A and DT of the E velocity were similar in the 2 groups, the OMI group had lower Ea and higher E/Ea compared with the Control group. Table 3 shows the right-sided echocardiographic data of the study subjects. Although RV area indices and FAC were similar in both groups, TAPSE was reduced and RV MPI was higher in the OMI group compared with the Control group. In the OMI group, 73% of patients had normal estimated peak systolic pulmonary artery pressure of less than 35 mmHg.

Speckle tracking was possible in 100% of the 3480 attempted segments from the 116 echocardiographic studies with technically adequate images. Table 4 and Figure 2 show comparisons of LV and RV strains between the Control and OMI groups. All strain values in the left ventricle were significantly reduced in the OMI group compared with those in the Control group. Notably, both global and free wall RV PSS were significantly reduced in the OMI group compared with those in the Control group (global RV PSS: -18.3 ± 5.9* vs. -25.5 ± 4.2%, and free wall RV PSS: -22.1 ± 7.5* vs. -26.9 ± 5.0%, *p <0.05 vs. the Control group, Figure 2).

Successful primary revascularization was not statistically associated with global or free wall RV PSS. We assessed the potential impact of infarcted site and residual total occlusion in the culprit lesion responsible for MI on RV function. When patients were divided into two groups according to median value of the global RV PSS: -19.1%, patients with reduced global RV PSS (−13 ± 4%) had a higher prevalence of residual total occlusion in the culprit right coronary artery than those with preserved global RV PSS (−23 ± 3%) (Table 5). There were 31 patients (44%) who received beta blockers. No statistically significant differences were observed in the values of global and free wall RV PSS between patients with and without beta-blocker therapy.

Since the time interval between the acute MI onset and the echocardiographic evaluation varied individually in the present study, we investigated the potential influence of the chronicity of MI on RV function. Patients <1 year after onset of MI had much more impaired global and free wall RV PSS than those ≥1 year after onset of MI among the 3 groups (global RV PSS: -21 ± 6% in patients <1 year, -17 ± 6*% in patients ≥1 year, and −18 ± 6% in patients with unknown duration, and free wall RV PSS: -25 ± 7% in patients <1 year, -20 ± 8*% in patients >1year, and −22 ± 7% in patients with unknown duration *p<0.05 vs. patients <1 year) although age, gender, log-transformed plasma BNP, and longitudinal LV PSS in the 4-chamber view were similar.

Tables 6 and 7 show the univariate correlation coefficients for clinical characteristics and echocardiography variables with global and free wall RV PSS, and the results of the stepwise multivariate regression analyses in the OMI group. Both global and free wall RV PSS were associated with heart rate, plasma BNP levels, chronicity of MI, LV mass index, PVR, LV PSS, and infarcted territories and the presence of residual total occlusion. Multivariable linear regression analysis indicated that longitudinal LV PSS in the 4-chamber view, BNP ≥500 pg/ml, and residual total occlusion in the culprit right coronary artery were the independent determinants of global RV strain. Longitudinal LV PSS in the 4-chamber view, BNP ≥500 pg/ml, MI in the territory of the left circumflex artery were the independent determinants of free wall RV PSS. When patients were divided into 3 groups according to plasma BNP levels (BNP <100 pg/ml; n = 31, 100 ≤BNP <500 pg/ml; n = 24, and BNP ≥500 pg/ml; n = 16), only patients with BNP ≥500 pg/ml had a strong correlation between RV strains and longitudinal LV PSS in the 4-chamber view (Figure 3) although global RV strain had modest correlation with longitudinal LV PSS patients with 100 ≤BNP <500 pg/ml. Figures 4 and 5 and Additional files 1, 2, 3, 4, 5, 6: Movies1-6 show typical examples of strain imaging (top) in the LV apical 4-chamber views (Figure 4) and RV apical 4-chamber views (Figure 5), and corresponding time-strain curves (bottom) in a normal subject, a patient with OMI and low plasma BNP level, and a patient with OMI and high plasma BNP level. The normal subject had preserved LV and RV regional strains through a cardiac cycle (Figures 4A and 5A, and Additional files 1 and 2: Movies for the LV and RV strain images, respectively). The patient with OMI in the territory of left anterior descending artery and low plasma BNP level (39 pg/ml) had mildly reduced segmental longitudinal LV strain in both the apical and apical anterolateral segments and normal free wall RV strain (Figures 4B and 5B, and Additional files 3 and 4: Movies for the LV and RV strain images, respectively). The patient with OMI in the all 3 coronary artery territories and high plasma BNP level (955 pg/ml) had severely reduced LV and RV strain (Figures 4C and 5C, and Additional files 5 and 6: Movies for the LV and RV strain images, respectively). Notably, this patient had non-dilated RV, normal FAC, and normal estimated peak systolic pulmonary artery pressure of 25 mmHg.

Kaplan–Meier event-free survival curves for the composite endpoint of heart failure hospitalization and cardiovascular death were constructed, and statistical differences between patients with preserved and reduced indices of RV function were assessed by the Log-rank test. During the follow-up periods, there were 6 events (17%) in patients with preserved global RV PSS above the median value, and 19 events (54%) in those with reduced global RV PSS. As shown in Figure 6, patients with reduced global RV PSS and those with reduced free wall RV PSS had a higher risk for composite heart failure hospitalization and cardiovascular death whereas conventional indices of RV function including RV FAC and TAPSE did not reach statistical significance probably because of small sample size.

Inter-observer and intra-observer variability were 5.7 ± 4.4 and 3.6 ± 3.8% for global RV PSS and 5.4 ± 3.6 and 3.8 ± 3.7% for free wall RV PSS.

Limitations of this study include the small sample size and retrospective nature of data collection. For example, although no significant relationships between RV an LV longitudinal functions both in patients with BNP <100 pg/ml and patient with 100 <BNP <500 pg/ml were observed, these results can be due to type 2 error. Furthermore, there was a heterogeneous distribution of RV function in our study population. Invasive pressure measurements were not used in this study. Therefore, peak systolic pulmonary artery pressure and PVR estimated by using Doppler echocardiography were recruited as markers of the severity of RV pressure overload. However, Doppler-derived estimations of these hemodynamic indices are widely recognized to work well with simultaneous catheter-derived measurements and are widely used clinically. Quantitative assessment of myocardial infarction size was not involved in the present study. Although we assessed the potential impact of residual total occlusion in the culprit lesion responsible for MI on RV function, the presence and severity of stress-induced myocardial ischemia was not evaluated in our study. Finally, three dimensional myocardial tracking in both the left and right ventricle would be warranted for the precise understanding of the pathophysiological mechanism responsible for RV functional impairments after MI.