Assami Rösner

Left ventricular size determines tissue Doppler-derived longitudinal strain and strain rate

AIMS Tissue Doppler-derived indices of strain (epsilon) and strain rate (SR) have been developed to assess regional cardiac function. However, the effect of left ventricular (LV) size on epsilon and SR has not been studied in depth. The aim of this study was to assess to what extent heart size influence epsilon or SR. METHODS AND RESULTS In 21 anaesthetized pigs ranging from 12.5 to 70.0 kg, tissue Doppler-derived epsilon and SR, and haemodynamic parameters, were assessed during controlled heart rates and different loading conditions. dP/dt did not correlate to pig weight, suggesting constant contractility during growth. Longitudinal epsilon and SR were significantly higher in smaller compared with larger hearts. The hyperbolic correlation between pigs weight and epsilon and SR was r(2)=0.621 and 0.372, respectively, both P<0.0001. Afterload elevation induced a reduction in longitudinal epsilon (from -24.2+/-3.2 to -12.1+/-5.5%, P=0.001) and SR (from -2.3+/-0.8 to -1.3+/-2.4 s(-1), P=0.034), whereas increasing preload increased epsilon (from -26.4+/-10.3 to -38.1+/-14.3%, P=0.006) and SR (from -2.3+/-0.9 to -4.22+/-1.8 s(-1), P=0.002). CONCLUSION Longitudinal epsilon and SR decrease with increasing LV dimensions in spite of an unaltered contractility. These results show and confirm that heart size influences epsilon and SR, which are highly load-dependent parameters.

The influence of frame rate on two-dimensional speckle-tracking strain measurements: a study on silico-simulated models and images recorded in patients

AIMS Ultrasound-derived myocardial strain can render valuable diagnostic and prognostic information. However, acquisition settings can have an important impact on the measurements. Frame rate (i.e. temporal resolution) seems to be of particular importance. The aim of this study was to find the optimal range of frame rates needed for most accurate and reproducible 2D strain measurements using a 2D speckle-tracking software package. METHODS AND RESULTS Synthetic two dimensional (2D) ultrasound grey-scale images of the left ventricle (LV) were generated in which the strain in longitudinal, circumferential, and radial direction were precisely known from the underlying kinematic LV model. Four different models were generated at frame rates between 20 and 110 Hz. The resulting images were repeatedly analysed. Results of the synthetic data were validated in 66 patients, where long- and short-axis recordings at different frame rates were analysed. In simulated data, accurate strain estimates could be achieved at >30 frames per cycle (FpC) for longitudinal and circumferential strains. Lower FpC underestimated strain systematically. Radial strain estimates were less accurate and less reproducible. Patient strain displayed the same plateaus as in the synthetic models. Higher noise and the presence of artefacts in patient data were followed by higher measurement variability. CONCLUSION Standard machine settings with a FR of 50-60 Hz allow correct assessment of peak global longitudinal and circumferential strain. Correct definition of the region of interest within the myocardium as well as the reduction of noise and artefacts seem to be of highest importance for accurate 2D strain estimation.

Heart Failure and Asymptomatic Left Ventricular Systolic Dysfunction in Lymphoma Survivors Treated With Autologous Stem-Cell Transplantation: A National Cross-Sectional Study

PURPOSE We aimed to determine the prevalence of left ventricular systolic dysfunction (LVSD), including symptomatic (ie, heart failure [HF]) and asymptomatic LVSD in adult lymphoma survivors (LSs) after autologous hematopoietic stem-cell transplantation (auto-HCT) and to identify risk factors for LVSD in this population. PATIENTS AND METHODS All LSs treated with auto-HCT as adults in Norway from 1987 to 2008 were eligible for this national cross-sectional study. Asymptomatic LVSD was defined as left ventricular ejection fraction less than 50% by echocardiography, and HF was defined according to current recommendations. The results in LSs were compared with those found in an age- and sex-matched (1:1) control group. RESULTS We examined 274 LSs (69% of all eligible survivors); 62% were men, the mean (± standard deviation) age was 56 ± 12 years, and mean follow-up time from lymphoma diagnosis was 13 ± 6 years. The mean cumulative doxorubicin dose was 316 ± 111 mg/m(2), and 35% of LSs had received additional radiation therapy involving the heart. We found LVSD in 15.7% of the LSs, of whom 5.1% were asymptomatic. HF patients were symptomatically mildly affected, with 8.8% of all LSs classified as New York Heart Association class II, whereas more severe HF was rare (1.8%). Compared with controls, LSs had a substantially increased LVSD risk (odds ratio, 6.6; 95% CI, 2.5 to 17.6; P < .001). A doxorubicin dose ≥ 300 mg/m(2) and cardiac radiation therapy dose greater than 30 Gy were independent risk factors for LVSD. CONCLUSION LVSD was frequent and HF more prevalent than previously reported in LSs after auto-HCT. Our results may help to identify LSs at increased LVSD risk and can serve as a basis for targeted surveillance strategies.

Dobutamine-norepinephrine, but not vasopressin, restores the ventriculoarterial matching in experimental cardiogenic shock.

We assessed the hemodynamic effects of guideline therapy in experimental cardiogenic shock and compared this treatment with a combination containing an alternative vasopressor (arginine vasopressin, AVP). Our hypothesis was that combined dobutamine-norepinephrine still is the superior inopressor therapy assessed by ventriculoarterial matching in both systole and diastole. Cardiogenic shock (CS) was induced by coronary microembolization in 16 pigs. Dobutamine (Dobu, 2ug/kg/min) alone and combined with either norepinephrine (NE, 100 ng/kg/min) or the pure vasopressor AVP (0.001 u/kg/min) were infused. In CS, Dobu increased cardiac output (CO) and central venous oxygen saturation (SVO₂) from 74 ± 3 mL/kg and 37 ± 2% to 103 ± 8 mL/kg and 49 ± 3%. Adding NE resulted in a further improvement of CO (125 ± 9 mL/kg) and SVO₂ (59 ± 4%) because of an increased heart rate and contractility with minimal change in systemic vascular resistance. Also, energy transfer from the ventricle to the arterial system was restored partly by Dobu and was normalized by supplementing NE. In contrast, supplemental AVP further worsened the shock state by decreasing CO (70 ± 6 mL/kg) and SVO₂ (45 ± 5%) compared with Dobu alone. Combined Dobu-NE has an efficient hemodynamic profile in CS. A pure afterload increasing substance used in acute ischemic CS aggravates the shock state by causing a ventriculoarterial mismatch despite its use in combination with an inotropic compound.

Peak longitudinal strain most accurately reflects myocardial segmental viability following acute myocardial infarction - an experimental study in open-chest pigs

BackgroundThe extension and the transmurality of the myocardial infarction are of high predictive value for clinical outcome. The aim of the study was to characterize the ability of longitudinal, circumferential and radial strain measured by 2-dimensional speckle tracking echocardiography (2D-STE) to predict the extent of necrosis in myocardial segments following acute myocardial infarction and to separate transmural necrotic segments from non-transmural necrotic segments in a full 18-segment porcine model.Methods2D-STE strain was assessed in long- and short-axis following myocardial infarction in ten open-chest anesthetized pigs. Strain was defined according to systolic peak values. In segments displaying both negative and positive peaks, only the peak with the highest absolute value was utilized. Necrosis was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining and expressed as percent of each myocardial segment.ResultsSignificant correlations were found between the extension of necrosis and all measured parameters of myocardial deformation (p < 0.001), but was stronger for longitudinal strain (r2 = 0.52) than circumferential strain (r2 = 0.38) and radial strain (r2 = 0.23). The area under the receiver operator characteristic curve (AUC) for separating transmural necrotic segments (>50% necrosis) from predominantly viable segments (0–50% necrosis) was significantly larger for longitudinal strain (AUC = 0.98, CI = 0.97–1.00) when compared with circumferential strain (AUC = 0.91, CI = 0.84–0.97, p < 0.05) and radial strain (AUC = 0.90, CI = 0.83 – 0.96, p < 0.01), indicating a stronger ability of longitudinal strain to identify segments with transmural necrosis.ConclusionPeak strain values derived from 2D-STE correlate well with the extent of necrosis in myocardial segments following acute myocardial infarction. Longitudinal strain most accurately reflects myocardial segmental viability in this setting.

Valvular Dysfunction in Lymphoma Survivors Treated with Autologous Stem Cell Transplantation A National Cross-Sectional Study

OBJECTIVES This study assessed the prevalence and associated risk factors for valvular dysfunction (VD) observed in adult lymphoma survivors (LS) after autologous hematopoietic stem cell transplantation (auto-HCT), and to determine whether anthracycline-containing chemotherapy (ACCT) alone in these patients is associated with VD. BACKGROUND The prevalence of and risk factors for VD in LS after auto-HCT is unknown. Anthracyclines may induce heart failure, but any association with VD is not well-defined. METHODS This national cross-sectional study included all adult LS receiving auto-HCT from 1987 to 2008 in Norway. VD was defined by echocardiography as either more than mild regurgitation or any stenosis. Observations in LS were compared with a healthy age- and gender-matched (1:1) control group. RESULTS In total, 274 LS (69% of all eligible) participated. Mean age was 56 ± 12 years, mean follow-up time after lymphoma diagnosis was 13 ± 6 years, and 62% of participants were males. Mean cumulative anthracycline dosage was 316 ± 111 mg/m(2), and 35% had received radiation therapy involving the heart (cardiac-RT). VD was observed in 22.3% of the LS. Severe VD was rare (n = 9; 3.3% of all LS) and mainly aortic stenosis (n = 7). We observed VD in 16.7% of LS treated with ACCT alone (n = 177), corresponding with a 3-fold increased VD risk (odds ratio: 2.9; 95% confidence interval: 1.5 to 5.8; p = 0.002) compared with controls. Furthermore, the presence of aortic valve degeneration was increased in the LS after ACCT alone compared with controls (13.0% vs. 2.9%; p < 0.001). Female sex, age >50 years at lymphoma diagnosis, ≥3 lines of chemotherapy before auto-HCT, and cardiac-RT >30 Gy were identified as independent risk factors for VD in the LS. CONCLUSIONS In LS, ACCT alone was significantly associated with VD and related to valvular degeneration. Overall, predominantly moderate VD was prevalent in LS, and longer observation time is needed to clarify the clinical significance of this finding.

Persistent dysfunction of viable myocardium after revascularization in chronic ischaemic heart disease: implications for dobutamine stress echocardiography with longitudinal systolic strain and strain rate measurements

AIMS Studies of functional recovery after revascularization in chronic coronary artery disease are contradictory and mark a lack of knowledge of persistent dysfunction in the non-scarred myocardium. Based on tissue Doppler-derived regional longitudinal systolic strain and strain rate (SR), both at rest and during dobutamine stress (DS), we assessed to what extent ischaemia-related reduced myocardial function would recover after revascularization in hearts with predominantly viable myocardium. METHODS AND RESULTS Reference peak systolic strain and SR values were determined from tissue Doppler imaging in 15 healthy volunteers. Fifty-seven patients scheduled for coronary artery bypass grafting (CABG), with an average ejection fraction of 49%, underwent pre-operative magnetic resonance imaging (MRI) with late enhancement, resting echocardiography, and DS echocardiography (DSE), with assessment of systolic strain and SR and post-systolic strain (PSS). Eight to 10 months after CABG, myocardial function was reassessed. Forty per cent of all segments had reduced longitudinal systolic strain pre-operatively despite only 1.4% of segments with transmural infarctions on MRI. After revascularization, 38% of prior dysfunctional segments improved their resting strain, whereas 72% were improved by DS. Positive resting systolic strain indicated the absence of significant scar tissue. Resting systolic strain and DS strain responses were good prognosticators for functional improvement with areas under the receiver operating characteristic curve of 0.753 (0.646-0.860) and 0.790 (0.685-0.895), respectively. CONCLUSION Persistently reduced longitudinal function was observed in more than half of pre-operatively viable but dysfunctional segments after CABG. We propose that such a functional impairment marks a regional remodelling process not amendable to re-established blood flow.

Oxygen Wasting Effect of inotropy—Is There a Need for a New Evaluation? An Experimental Large Animal Study Using Dobutamine and Levosimendan

Background— We addressed the hypothesis that the inotropic drugs dobutamine and levosimendan both induce surplus oxygen consumption (oxygen wasting) relative to their contractile effect in equipotent therapeutic doses, with levosimendan being energetically more efficient. Methods and Results— Postischemically reduced left ventricular function (stunning) was created by repetitive left coronary occlusions in 22 pigs. This contractile dysfunction was reversed by infusion of either levosimendan (24 μg/kg loading and 0.04 μg · kg−1 · min−1 infusion) or an equipotent dose of dobutamine (1.25 μg · kg−1 · min−1). Contractility and cardiac output were normalized by both drug regimens. The energy cost of drug-induced contractility enhancement was assessed by myocardial oxygen consumption related to the mechanical indexes tension-time index, pressure-volume area, and total mechanical energy. ANCOVA did not reveal any increased oxygen cost of contractility for either drug in these doses. However, both dobutamine and levosimendan at supratherapeutic levels (10 μg · kg−1 · min−1 and 48 μg/kg loading with 0.2 μg · kg−1 · min−1 infusion, respectively) induced a highly significant increase in oxygen consumption related to mechanical work, compatible with the established oxygen-wasting effect of inotropy ( P <0.001 for all mechanical indexes with dobutamine; P =0.007 for levosimendan as assessed by pressure-volume area). Conclusion— Therapeutic levels of neither dobutamine nor levosimendan showed inotropic oxygen wasting in this in vivo pig model. Thus, relevant hemodynamic responses can be achieved with an adrenergic inotrope without surplus oxygen consumption. Received March 17, 2009; accepted November 16, 2009.Background—We addressed the hypothesis that the inotropic drugs dobutamine and levosimendan both induce surplus oxygen consumption (oxygen wasting) relative to their contractile effect in equipotent therapeutic doses, with levosimendan being energetically more efficient. Methods and Results—Postischemically reduced left ventricular function (stunning) was created by repetitive left coronary occlusions in 22 pigs. This contractile dysfunction was reversed by infusion of either levosimendan (24 &mgr;g/kg loading and 0.04 &mgr;g·kg−1·min−1 infusion) or an equipotent dose of dobutamine (1.25 &mgr;g·kg−1·min−1). Contractility and cardiac output were normalized by both drug regimens. The energy cost of drug-induced contractility enhancement was assessed by myocardial oxygen consumption related to the mechanical indexes tension-time index, pressure-volume area, and total mechanical energy. ANCOVA did not reveal any increased oxygen cost of contractility for either drug in these doses. However, both dobutamine and levosimendan at supratherapeutic levels (10 &mgr;g·kg−1·min−1 and 48 &mgr;g/kg loading with 0.2 &mgr;g·kg−1·min−1 infusion, respectively) induced a highly significant increase in oxygen consumption related to mechanical work, compatible with the established oxygen-wasting effect of inotropy (P<0.001 for all mechanical indexes with dobutamine; P=0.007 for levosimendan as assessed by pressure-volume area). Conclusion—Therapeutic levels of neither dobutamine nor levosimendan showed inotropic oxygen wasting in this in vivo pig model. Thus, relevant hemodynamic responses can be achieved with an adrenergic inotrope without surplus oxygen consumption.

High Resolution Speckle Tracking Dobutamine Stress Echocardiography Reveals Heterogeneous Responses in Different Myocardial Layers: Implication for Viability Assessments

BACKGROUND Speckle-tracking echocardiography (STE) can be used to quantify wall strain in 3 dimensions and thus has the potential to improve the identification of hypokinetic but viable myocardium on dobutamine stress echocardiography (DSE). However, if different myocardial layers respond heterogeneously, STE-DSE will have to be standardized according to strain dimension and the positioning of the region of interest. Therefore, the aim of this study was to create a high-resolution model for ejection time (ET) strain and tissue flow in 4 myocardial layers at rest, during hypoperfusion, and during dobutamine challenge to assess the ability of STE-DSE to detect deformation and functional improvement in various layers of the myocardium. METHODS In 10 open chest pigs, the left anterior descending coronary artery was constricted to a constant stenosis, resulting in 35% initial flow reduction. Fluorescent microspheres were used to measure tissue flow. High-resolution echocardiography was performed epicardially to calculate ET strain in 4 myocardial layers in the radial, longitudinal, and circumferential directions using speckle-tracking software. Images were obtained at rest, during left anterior descending coronary artery constriction (hypoperfusion), and during a subsequent dobutamine stress period. RESULTS Dobutamine stress at constant coronary stenosis increased flow in all layers. ET strain increased predominantly in the midmyocardial layers in the longitudinal and circumferential directions, whereas subendocardial strain did not improve in either direction. CONCLUSION Dobutamine stress influences ET strain differently in the various axes and layers of the myocardium and only partially in correspondence to tissue flow. Longitudinal and circumferential functional reserve opens the potential for the specific detection of midsubendocardial viable tissue by high-resolution STE.

Oxygen-Wasting Effect of InotropyCLINICAL PERSPECTIVE

Background— We addressed the hypothesis that the inotropic drugs dobutamine and levosimendan both induce surplus oxygen consumption (oxygen wasting) relative to their contractile effect in equipotent therapeutic doses, with levosimendan being energetically more efficient. Methods and Results— Postischemically reduced left ventricular function (stunning) was created by repetitive left coronary occlusions in 22 pigs. This contractile dysfunction was reversed by infusion of either levosimendan (24 μg/kg loading and 0.04 μg · kg−1 · min−1 infusion) or an equipotent dose of dobutamine (1.25 μg · kg−1 · min−1). Contractility and cardiac output were normalized by both drug regimens. The energy cost of drug-induced contractility enhancement was assessed by myocardial oxygen consumption related to the mechanical indexes tension-time index, pressure-volume area, and total mechanical energy. ANCOVA did not reveal any increased oxygen cost of contractility for either drug in these doses. However, both dobutamine and levosimendan at supratherapeutic levels (10 μg · kg−1 · min−1 and 48 μg/kg loading with 0.2 μg · kg−1 · min−1 infusion, respectively) induced a highly significant increase in oxygen consumption related to mechanical work, compatible with the established oxygen-wasting effect of inotropy ( P <0.001 for all mechanical indexes with dobutamine; P =0.007 for levosimendan as assessed by pressure-volume area). Conclusion— Therapeutic levels of neither dobutamine nor levosimendan showed inotropic oxygen wasting in this in vivo pig model. Thus, relevant hemodynamic responses can be achieved with an adrenergic inotrope without surplus oxygen consumption. Received March 17, 2009; accepted November 16, 2009.Background—We addressed the hypothesis that the inotropic drugs dobutamine and levosimendan both induce surplus oxygen consumption (oxygen wasting) relative to their contractile effect in equipotent therapeutic doses, with levosimendan being energetically more efficient. Methods and Results—Postischemically reduced left ventricular function (stunning) was created by repetitive left coronary occlusions in 22 pigs. This contractile dysfunction was reversed by infusion of either levosimendan (24 &mgr;g/kg loading and 0.04 &mgr;g·kg−1·min−1 infusion) or an equipotent dose of dobutamine (1.25 &mgr;g·kg−1·min−1). Contractility and cardiac output were normalized by both drug regimens. The energy cost of drug-induced contractility enhancement was assessed by myocardial oxygen consumption related to the mechanical indexes tension-time index, pressure-volume area, and total mechanical energy. ANCOVA did not reveal any increased oxygen cost of contractility for either drug in these doses. However, both dobutamine and levosimendan at supratherapeutic levels (10 &mgr;g·kg−1·min−1 and 48 &mgr;g/kg loading with 0.2 &mgr;g·kg−1·min−1 infusion, respectively) induced a highly significant increase in oxygen consumption related to mechanical work, compatible with the established oxygen-wasting effect of inotropy (P<0.001 for all mechanical indexes with dobutamine; P=0.007 for levosimendan as assessed by pressure-volume area). Conclusion—Therapeutic levels of neither dobutamine nor levosimendan showed inotropic oxygen wasting in this in vivo pig model. Thus, relevant hemodynamic responses can be achieved with an adrenergic inotrope without surplus oxygen consumption.