Anders Opdahl

Myocardial strain imaging: how useful is it in clinical decision making?

Abstract Myocardial strain is a principle for quantification of left ventricular (LV) function which is now feasible with speckle-tracking echocardiography. The best evaluated strain parameter is global longitudinal strain (GLS) which is more sensitive than left ventricular ejection fraction (LVEF) as a measure of systolic function, and may be used to identify sub-clinical LV dysfunction in cardiomyopathies. Furthermore, GLS is recommended as routine measurement in patients undergoing chemotherapy to detect reduction in LV function prior to fall in LVEF. Intersegmental variability in timing of peak myocardial strain has been proposed as predictor of risk of ventricular arrhythmias. Strain imaging may be applied to guide placement of the LV pacing lead in patients receiving cardiac resynchronization therapy. Strain may also be used to diagnose myocardial ischaemia, but the technology is not sufficiently standardized to be recommended as a general tool for this purpose. Peak systolic left atrial strain is a promising supplementary index of LV filling pressure. The strain imaging methodology is still undergoing development, and further clinical trials are needed to determine if clinical decisions based on strain imaging result in better outcome. With this important limitation in mind, strain may be applied clinically as a supplementary diagnostic method.

Determinants of Left Ventricular Early-Diastolic Lengthening Velocity Independent Contributions From Left Ventricular Relaxation, Restoring Forces, and Lengthening Load

Background— Peak early-diastolic mitral annulus velocity (e′) by tissue Doppler imaging has been introduced as a clinical marker of diastolic function. This study investigates whether lengthening load (early-diastolic load) and restoring forces are determinants of e′ in addition to rate of left ventricular (LV) relaxation. Methods and Results— In 10 anesthetized dogs, we measured e′ by sonomicrometry and tissue Doppler imaging during baseline, volume loading, caval constriction, dobutamine infusion, and occlusion of the left anterior descending coronary artery. Relaxation was measured as the time constant (&tgr;) of LV pressure decay by micromanometer. Lengthening load was measured as LV transmural pressure at mitral valve opening (LVPMVO). Restoring forces were quantified by 2 different indices: (1) As the difference between minimum and unstressed LV diameter (Lmin−L0) and (2) as the estimated fully relaxed LV transmural pressure (FRPEst) at minimum diameter. In the overall analysis, a strong association was observed between e′ and LVPMVO (&bgr;=0.49; P<0.001), which indicates an independent effect of lengthening load, as well as between e′ and Lmin−L0 (&bgr;=−0.38; P<0.002) and between e′ and FRPEst (&bgr;=−0.31; P<0.002), consistent with an independent contribution of restoring forces. A direct effect of rate of relaxation on e′ was observed in a separate analysis of baseline, dobutamine, and ischemia when postextrasystolic beats were included (&bgr;=−0.06, P<0.01). Conclusions— The present study indicates that in the nonfailing ventricle, in addition to LV relaxation, restoring forces and lengthening load are important determinants of early-diastolic lengthening velocity.

Apical Rotation by Speckle Tracking Echocardiography: A Simplified Bedside Index of Left Ventricular Twist

OBJECTIVE The study objective was to determine whether left ventricular (LV) apical rotation by speckle tracking echocardiography (STE) may serve as a clinically feasible index of LV twist. LV twist has been proposed as a sensitive marker of LV function, but clinical implementation has not been feasible because of the complexity and limitations of present methodologies. METHODS The relationship between apical rotation and LV twist was investigated in anesthetized dogs (n = 9) and a clinical study that included healthy controls (n = 18) and patients (n = 27) with previous myocardial infarction. Rotation by STE was compared with twist measured by magnetic resonance imaging and sonomicrometry in humans and dogs, respectively. RESULTS In dogs, apical rotation by STE correlated well with LV twist over a wide range of loading conditions and inotropic states, and during myocardial ischemia (R = 0.94, P < .01). Similarly, in humans there was a strong correlation between apical rotation and twist (R = 0.88, P < .01) but only a weak correlation between basal rotation and twist (R = 0.53, P < .01). Apical rotation accounted for 72% +/- 14% and 73% +/- 15% of the twisting deformation by magnetic resonance imaging in controls and patients, respectively. In dogs, apical rotation and twist decreased during myocardial ischemia (P < .05). In patients, LV twist and apical rotation were reduced (P < .05) only when LV ejection fraction was less than 50%. CONCLUSION Apical rotation represents the dominant contribution to LV twist, and apical rotation by STE reflects LV twist over a wide range of hemodynamic conditions. These findings suggest that apical rotation by STE may serve as a simple and feasible clinical index of LV twist.

Myocardial strain analysis in acute coronary occlusion : A tool to assess myocardial viability and reperfusion

Background— This study proposes 2 new echocardiographic indices with potential application in acute coronary artery occlusion to differentiate between viable and necrotic myocardium and to identify reperfusion. We investigated whether the ratio between systolic lengthening and combined late and postsystolic shortening (L-S ratio) could identify viable myocardium and whether systolic myocardial compliance, calculated as systolic lengthening divided by systolic pressure rise, could identify necrotic myocardium. Methods and Results— In anesthetized dogs, we measured left ventricular (LV) pressure and long-axis strain by Doppler echocardiography (SDE) and sonomicrometry. The left anterior descending coronary artery was occluded for 15 minutes with 3-hour reperfusion (n=6), for 4 hours with 3-hour reperfusion (n=6), or for 4 hours with no reperfusion (n=6). Myocardial work was quantified by pressure–segment length analysis, necrosis by triphenyltetrazolium chloride staining, and edema by water content. L-S ratio and systolic compliance were calculated by SDE. The L-S ratio ranged between 0.00 and 1.00 and was well correlated with regional myocardial work (r=0.77, P<0.0001). In entirely passive myocardium, the L-S ratio approached 1 and was similar in viable (0.88±0.02) and necrotic (0.81±0.03) myocardium. Compliance, however, was reduced in necrotic myocardium owing to edema (0.07±0.01%/mm Hg) but was preserved in viable myocardium (0.15±0.01%/mm Hg, P<0.05). Reperfusion of viable myocardium caused a reduction of the L-S ratio after 15 minutes (0.57±0.06, P<0.05), reflecting recovery of function. Reperfusion of necrotic myocardium caused no change in the L-S ratio, but compliance was further reduced within 15 minutes (0.03±0.01%/mm Hg, P<0.05). Conclusion— Myocardial L-S ratio and compliance by SDE identified active contraction and necrosis, respectively. These indices should be tested clinically for assessment of myocardial viability and reperfusion.

Prognostic value of myocardial circumferential strain for incident heart failure and cardiovascular events in asymptomatic individuals: the Multi-Ethnic Study of Atherosclerosis

AIMS Left ventricular (LV) circumferential strain (Ecc) is a sensitive index of regional myocardial function. Currently, no studies have assessed its prognostic value in general population. We sought to investigate whether Ecc has a prognostic value for predicting incident heart failure (HF) and other major cardiovascular events in asymptomatic individuals without a history of previous cardiovascular diseases. METHODS AND RESULTS We, prospectively, assessed incident HF and atherosclerotic events during a 5.5 ± 1.3-year period in 1768 asymptomatic individuals aged 45-84 (mean age 65 years; 47% female) who underwent tagged magnetic resonance imaging for strain determination. During the follow-up period, 39 (2.2%) participants experienced incident HF and 108 (6.1%) participants had atherosclerotic cardiovascular events. Average of peak Ecc of 12-LV segments (Ecc-global) and mid-slice (Ecc-mid) was -17.0 ± 2.4 and -17.5 ± 2.7%, respectively. Participants with average absolute Ecc-mid lower than -16.9% had a higher cumulative hazard of incident HF (log-rank test, P = 0.001). In cox regression analysis, Ecc-mid predicted incident HF independent of age, diabetes status, hypertension, interim myocardial infarction, LV mass index, and LV ejection fraction (hazard ratio 1.15 per 1%, 95% CI: 1.01-1.31, P = 0.03). This relationship remained significant after adjustment for LV-end-systolic wall stress into covariates. In addition, by adding Ecc-mid to risk factors, LV ejection fraction, and the LV mass index, both the global χ(2) value (76.6 vs. 82.4, P = 0.04) and category-less net-reclassification index (P = 0.01, SE = 0.18, z = 2.53) were augmented for predicting HF. Circumferential strain was also significantly related to the composite atherosclerotic cardiovascular events, but its relationship was attenuated after introducing the LV mass index. CONCLUSION Circumferential shortening provides robust, independent, and incremental predictive value for incident HF in asymptomatic subjects without any history of previous clinical cardiovascular disease. CLINICAL TRIAL REGISTRATION http://www.clinicaltrials.gov. Unique identifier: NCT00005487.

Association of CMR-Measured LA Function With Heart Failure Development: Results From the MESA Study

OBJECTIVES The goal of this study was to assess the association between left atrial (LA) volume and function measured with feature-tracking cardiac magnetic resonance (CMR) and development of heart failure (HF) in asymptomatic individuals. BACKGROUND Whether alterations of LA structure and function precede or follow HF development remains incompletely understood. We hypothesized that significant alterations of LA deformation and architecture precede the development of HF in the general population. METHODS In a case-control study nested in MESA (Multi-Ethnic Study of Atherosclerosis), baseline LA volume and function assessed using CMR feature-tracking were compared between 112 participants with incident HF (mean age 68.4 ± 8.2 years; 66% men) and 224 age- and sex-matched controls (mean age 67.7 ± 8.9 years; 66% men). Participants were followed up for 8 years. All individuals were in normal sinus rhythm at the time of imaging, without any significant valvular abnormalities and free of clinical cardiovascular diseases. RESULTS Individuals with incident HF had greater maximal and minimal LA volume indexes (LAVImin) than control subjects (40 ± 13 mm(3)/m(2) vs. 33 ± 10 mm(3)/m(2) [p <0.001] for maximal LA index and 25 ± 11 mm(3)/m(2) vs. 17 ± 7 mm(3)/m(2) [p <0.001] for LAVImin). The HF case subjects also had smaller global peak longitudinal atrial strain (PLAS) (25 ± 11% vs. 38 ± 16%; p <0.001) and lower LA emptying fraction (40 ± 11% vs. 48 ± 9%; p <0.001) at baseline. After adjustment for traditional cardiovascular risk factors, left ventricular mass, and N-terminal pro-B-type natriuretic peptide, global PLAS (odds ratio: 0.36 per SD [95% confidence interval: 0.22 to 0.60]) and LAVImin (odds ratio: 1.65 per SD [95% confidence interval: 1.04 to 2.63]) were independently associated with incident HF. CONCLUSIONS Deteriorations in LA structure and function preceded development of HF. Lower global PLAS and higher LAVImin, measured using CMR feature-tracking, were independent markers of incident HF in a multiethnic population of asymptomatic individuals.

Resting Heart Rate as Predictor for Left Ventricular Dysfunction and Heart Failure: MESA (Multi-Ethnic Study of Atherosclerosis)

OBJECTIVES The objective of this study was to investigate the relationship between baseline resting heart rate and incidence of heart failure (HF) and global and regional left ventricular (LV) dysfunction. BACKGROUND The association of resting heart rate to HF and LV function has not been well described in an asymptomatic multi-ethnic population. METHODS Resting heart rate was measured in participants in the MESA (Multi-Ethnic Study of Atherosclerosis) trial at inclusion. Incident HF was registered (n = 176) during follow-up (median 7 years) in those who underwent cardiac magnetic resonance imaging (n = 5,000). Changes in ejection fraction (ΔEF) and peak circumferential strain (Δεcc) were measured as markers of developing global and regional LV dysfunction in 1,056 participants imaged at baseline and 5 years later. Time to HF (Cox model) and Δεcc and ΔEF (multiple linear regression models) were adjusted for demographics, traditional cardiovascular risk factors, calcium score, LV end-diastolic volume, and mass in addition to resting heart rate. RESULTS Cox analysis demonstrated that for 1 beat/min increase in resting heart rate, there was a 4% greater adjusted relative risk for incident HF (hazard ratio: 1.04; 95% CI: 1.02 to 1.06; p < 0.001). Adjusted multiple regression models demonstrated that resting heart rate was positively associated with deteriorating εcc and decrease in EF, even when all coronary heart disease events were excluded from the model. CONCLUSIONS Elevated resting heart rate was associated with increased risk for incident HF in asymptomatic participants in the MESA trial. Higher heart rate was related to development of regional and global LV dysfunction independent of subclinical atherosclerosis and coronary heart disease. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487).

Mechanisms of Abnormal Systolic Motion of the Interventricular Septum During Left Bundle-Branch Block

Background— In a majority of patients with left bundle-branch block (LBBB), there is abnormal leftward motion of the interventricular septum during the preejection phase. This motion was considered to be passive, caused by early rise in right ventricular (RV) pressure, and has therefore been excluded from most indices of left ventricular (LV) dyssynchrony. If considered active, however, the leftward motion reflects onset of septal activation and should be included. We therefore investigated if the motion was a passive response to pressure changes or caused by active contraction. Methods and Results— LBBB was induced in 8 anesthetized dogs with micromanometers. Cardiac dimensions were measured by sonomicrometry and echocardiography. Induction of LBBB resulted in preejection leftward motion of the septum, simultaneously with shortening of septal segments (P<0.01). In each experiment, preejection septal shortening occurred against rising LV pressure, consistent with active contraction. Furthermore, the LV pressure–segment length relationships were shifted upward (P<0.01) relative to the passive elastic curve, indicating stiffening of septal myocardium, confirming an active mechanism. Initially, RV pressure increased faster than LV pressure, suggesting that the leftward septal motion may have a passive pressure component. However, the passive component appeared to play a minor role. The magnitude of preejection septal shortening was modified by load alterations. Conclusions— Leftward preejection motion of the septum during LBBB is mainly a result of active septal contraction, whereas alterations in diastolic ventricular pressures modulate the amplitude of this motion. The findings imply that the preejection phase should be included when assessing LV dyssynchrony.

N-terminal Pro-B-Type Natriuretic Peptide, Left Ventricular Mass, and Incident Heart Failure: Multi-Ethnic Study of Atherosclerosis

Background—Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with clinically overt heart failure (HF). However, whether it provides additive prognostic information for incident HF beyond traditional risk factors and left ventricular (LV) mass index among multi-ethnic asymptomatic individuals has not yet been determined. We studied the associations of plasma NT-proBNP and magnetic resonance imaging defined LV mass index with incident HF in an asymptomatic multi-ethnic population. Methods and Results—A total of 5597 multi-ethnic participants without clinically apparent cardiovascular disease underwent baseline measurement of NT-proBNP and were followed for 5.5±1.1 years. Among them, 4163 also underwent baseline cardiac magnetic resonance imaging. During follow-up, 111 participants experienced incident HF. Higher NT-proBNP was significantly associated with incident HF, independent of baseline age, sex, ethnicity, systolic blood pressure, diabetes mellitus, smoking, estimated glomerular filtration rate, medications (anti-hypertensive and statin), LV mass index, and interim myocardial infarction (hazard ratio: 1.95 per 1U log NT-proBNP increment, 95% CI 1.54–2.46, P<0.001). This relationship held among different ethnic groups, non-Hispanic whites, African-Americans, and Hispanics. Most importantly, NT-proBNP provided additive prognostic value beyond both traditional risk factors and LV mass index for predicting incident HF (integrated discrimination index=0.046, P<0.001; net reclassification index; 6-year risk probability categorized by <3%, 3–10%, >10% =0.175, P=0.019; category-less net reclassification index=0.561, P<0.001). Conclusions—Plasma NT-proBNP provides incremental prognostic information beyond traditional risk factors and the magnetic resonance imaging-determined LV mass index for incident symptomatic HF in an asymptomatic multi-ethnic population. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005487.

Myocardial Relaxation, Restoring Forces, and Early-Diastolic Load Are Independent Determinants of Left Ventricular Untwisting Rate

Background— Peak left ventricular (LV) untwisting rate (UTR) has been introduced as a clinical marker of diastolic function. This study investigates if early-diastolic load and restoring forces are determinants of UTR in addition to the rate of LV relaxation. Methods and Results— In 10 anesthetized dogs we measured UTR by sonomicrometry and speckle tracking echocardiography at varying LV preloads, increased contractility, and myocardial ischemia. UTR was calculated as the time derivative of LV twist. Because preload modified end-diastolic twist, LV systolic twist was calculated in absolute terms with reference to the end-diastolic twist configuration at baseline. Relaxation rate was measured as the time constant (&tgr;) of LV isovolumic pressure decay. Early-diastolic load was measured as LV pressure at the time of mitral valve opening. Circumferential-longitudinal shear strain was used as an index of restoring forces. In a multivariable mixed model analysis a strong association was observed between UTR and LV pressure at the time of mitral valve opening (parameter estimate [&bgr;]=6.9; P<0.0001), indicating an independent effect of early-diastolic load. Furthermore, the associations between UTR and circumferential-longitudinal shear strain (&bgr;=−11.3; P<0.0001) and &tgr; (&bgr;=−1.6, P<0.003) were consistent with independent contributions from restoring forces and rate of relaxation. Maximal UTR before mitral valve opening, however, was determined only by relaxation rate and restoring forces. Conclusions— The present study indicates that early-diastolic load, restoring forces, and relaxation rate are independent determinants of peak UTR. However, only relaxation rate and restoring forces contributed to UTR during isovolumic relaxation.