Regional Myocardial Contractile Function Research Articles

Computational Analysis of Cardiac Contractile Function.

Heart failure results in the high incidence and mortality all over the world. Mechanical properties of myocardium are critical determinants of cardiac function, with regional variations in myocardial contractility demonstrated within infarcted ventricles. Quantitative assessment of cardiac contractile function is therefore critical to identify myocardial infarction for the early diagnosis and therapeutic intervention. Current advancement of cardiac functional assessments is in pace with the development of imaging techniques. The methods tailored to advanced imaging have been widely used in cardiac magnetic resonance, echocardiography, and optical microscopy. In this review, we introduce fundamental concepts and applications of representative methods for each imaging modality used in both fundamental research and clinical investigations. All these methods have been designed or developed to quantify time-dependent 2-dimensional (2D) or 3D cardiac mechanics, holding great potential to unravel global or regional myocardial deformation and contractile function from end-systole to end-diastole. Computational methods to assess cardiac contractile function provide a quantitative insight into the analysis of myocardial mechanics during cardiac development, injury, and remodeling.

Myocardial Ischemia: Lack of Coronary Blood Flow or Myocardial Oxygen Supply/Demand Imbalance?

Regional myocardial blood flow and contractile function in ischemic myocardium are well matched, and there is no evidence for an oxygen supply/demand imbalance. Thus, myocardial ischemia is lack of coronary blood flow with electric, functional, metabolic, and structural consequences for the myocardium. All therapeutic interventions must aim to improve blood flow to ischemic myocardium as much and as quickly as possible.

Ivabradine: Cardioprotection By and Beyond Heart Rate Reduction

Ivabradine inhibits hyperpolarization-activated cyclic nucleotide-gated channels in the sinus node, thereby reducing heart rate, and heart rate reduction improves regional myocardial blood flow and contractile function in ischemic myocardium. Accordingly, ivabradine reduces anginal symptoms in patients with stable coronary artery disease but does not improve their clinical outcome. Heart rate reduction with ivabradine in patients with symptomatic heart failure reduces symptoms, attenuates remodeling, and improves clinical outcome. In pigs and mice, ivabradine reduces infarct size from myocardial ischemia/reperfusion, even when heart rate reduction is abrogated by atrial pacing. Improved viability is also observed in isolated ventricular cardiomyocytes subjected to simulated ischemia/reperfusion. These beneficial effects are attributed to reduced reactive oxygen species formation from the mitochondria. There is also evidence for a heart rate-independent benefit from ivabradine in the vasculature of mice and humans, and in left ventricular contractile function of pigs. Finally, in mice, ivabradine also has anti-aging potential.

Myocardial hypertrophy and its role in heart failure with preserved ejection fraction.

Left ventricular hypertrophy (LVH) is the most common myocardial structural abnormality associated with heart failure with preserved ejection fraction (HFpEF). LVH is driven by neurohumoral activation, increased mechanical load, and cytokines associated with arterial hypertension, chronic kidney disease, diabetes, and other comorbidities. Here we discuss the experimental and clinical evidence that links LVH to diastolic dysfunction and qualifies LVH as one diagnostic marker for HFpEF. Mechanisms leading to diastolic dysfunction in LVH are incompletely understood, but may include extracellular matrix changes, vascular dysfunction, as well as altered cardiomyocyte mechano-elastical properties. Beating cardiomyocytes from HFpEF patients have not yet been studied, but we and others have shown increased Ca(2+) turnover and impaired relaxation in cardiomyocytes from hypertrophied hearts. Structural myocardial remodeling can lead to heterogeneity in regional myocardial contractile function, which contributes to diastolic dysfunction in HFpEF. In the clinical setting of patients with compound comorbidities, diastolic dysfunction may occur independently of LVH. This may be one explanation why current approaches to reduce LVH have not been effective to improve symptoms and prognosis in HFpEF. Exercise training, on the other hand, in clinical trials improved exercise tolerance and diastolic function, but did not reduce LVH. Thus current clinical evidence does not support regression of LVH as a surrogate marker for (short-term) improvement of HFpEF.

Impact of Preserved Myocardial Contractile Function in the Segments Attached to the Papillary Muscles on Reduction in Functional Mitral Regurgitation

Effectiveness of functional mitral regurgitation (FMR) in heart failure patients is of growing importance for patient prognosis. The purpose of this study was to investigate whether regional myocardial contractile function as assessed by tissue Doppler strain rate imaging can predict reduction in FMR caused by dobutamine. Fifty-one patients with depressed left ventricular (LV) ejection fraction (32±9%) secondary to dilated cardiomyopathy and FMR underwent evaluation of effective regurgitant orifice (ERO) of FMR, mitral valve deformation, global LV remodeling, and regional myocardial contractile function assessed by longitudinal peak systolic strain rate (Ssr) in 6 mid-LV segments from standard apical views. We also determined the average Ssr of segments attached to the papillary muscles, that is, the inferior, inferolateral, and anterolateral segments (PM segments Ssr). Low-dose (10μg/kg per minute) dobutamine-induced reduction in ERO was compared with baseline variables. Baseline valve tenting was associated with dobutamine-induced reduction in ERO (r=-0.30, P<0.05). Receiver operating characteristic curve analysis showed that baseline valve tenting, LV sphericity index, inferior Ssr, inferolateral Ssr, and PM segments Ssr were predictors of dobutamine-induced ≥30% reduction in ERO. Importantly, only PM segments Ssr predicted dobutamine-induced ≥20% reduction in valve tenting with area under the curve of 0.67 (P<0.05). Preserved myocardial contractile function in the segments attached to the PMs was associated with dobutamine-induced reduction in mitral valve tenting and FMR, suggesting that our findings are important for improvement in cardiac function and FMR with medical treatment.

INTEGRATED PROTEOMIC AND METABOLOMIC ANALYSIS REVEALS NADH-MEDIATED TCA ENERGY METABOLISM DISORDER IN CHRONIC PROGRESSIVE HEART FAILURE

ObjectivesAlthough great progress has been made in heart failure (HF), it is still the major cause of mortality and morbidity worldwide. Typically, research associated with heart failure has focused on...

Cell-to-cell variability in troponin I phosphorylation in a porcine model of pacing-induced heart failure

We tested the hypothesis that myocardial contractile protein phosphorylation and the Ca2+ sensitivity of force production are dysregulated in a porcine model of pacing-induced heart failure (HF). The level of protein kinase A (PKA)-dependent cardiac troponin I (TnI) phosphorylation was lower in the myocardium surrounding the pacing electrode (pacing site) of the failing left ventricle (LV) than in the controls. Immunohistochemical assays of the LV pacing site pointed to isolated clusters of cardiomyocytes exhibiting a reduced level of phosphorylated TnI. Flow cytometry on isolated and permeabilized cardiomyocytes revealed a significantly larger cell-to-cell variation in the level of TnI phosphorylation of the LV pacing site than in the opposite region in HF or in either region in the controls: the interquartile range (IQR) on the distribution histogram of relative TnI phosphorylation was wider at the pacing site (IQR = 0.53) than that at the remote site of HF (IQR = 0.42; P = 0.0047) or that of the free wall of the control animals (IQR = 0.36; P = 0.0093). Additionally, the Ca2+ sensitivities of isometric force production were higher and appeared to be more variable in single permeabilized cardiomyocytes from the HF pacing site than in the healthy myocardium. In conclusion, the level of PKA-dependent TnI phosphorylation and the Ca2+ sensitivity of force production exhibited a high cell-to-cell variability at the LV pacing site, possibly explaining the abnormalities of the regional myocardial contractile function in a porcine model of pacing-induced HF.Electronic supplementary materialThe online version of this article (doi:10.1007/s00395-012-0244-x) contains supplementary material, which is available to authorized users.

Myocardial perfusion and contraction in acute ischemia and chronic ischemic heart disease

A large body of evidence has demonstrated that there is a close coupling between regional myocardial perfusion and contractile function. When ischemia is mild, this can result in the development of a new balance between supply and energy utilization that allows the heart to adapt for a period of hours over which myocardial viability can be maintained, a phenomenon known as "short-term hibernation". Upon reperfusion after reversible ischemia, regional myocardial function remains depressed. The "stunned myocardium" recovers spontaneously over a period of hours to days. The situation in myocardium subjected to chronic repetitive ischemia is more complex. Chronic dysfunction can initially reflect repetitive stunning with insufficient time for the heart to recover between episodes of spontaneous ischemia. As the frequency and/or severity of ischemia increases, the heart undergoes a series of adaptations which downregulate metabolism to maintain myocyte viability at the expense of contractile function. The resulting "hibernating myocardium" develops regional myocyte cellular hypertrophy as a compensatory response to ischemia-induced apoptosis along with a series of molecular adaptations that while regional, are similar to global changes found in advanced heart failure. As a result, flow-function relations become independently affected by tissue remodeling and interventions that stimulate myocyte regeneration. Similarly, chronic vascular remodeling may alter flow regulation in a fashion that increases myocardial vulnerability to ischemia. Here we review our current understanding of myocardial flow-function relations during acute ischemia in normal myocardium and highlight newly identified complexities in their interpretation in viable chronically dysfunctional myocardium with myocyte cellular and molecular remodeling. This article is part of a Special Issue entitled "Coronary Blood Flow".

Stem Cells in Heart Failure

Stem Cells in Heart Failure

Embryonic Stem Cell-Derived Cardiomyocyte Heterogeneity and the Isolation of Immature and Committed Cells for Cardiac Remodeling and Regeneration

Pluripotent stem cells represent one promising source for cell replacement therapy in heart, but differentiating embryonic stem cell-derived cardiomyocytes (ESC-CMs) are highly heterogeneous and show a variety of maturation states. In this study, we employed an ESC clonal line that contains a cardiac-restricted ncx1 promoter-driven puromycin resistance cassette together with a mass culture system to isolate ESC-CMs that display traits characteristic of very immature CMs. The cells display properties of proliferation, CM-restricted markers, reduced mitochondrial mass, and hypoxia-resistance. Following transplantation into rodent hearts, bioluminescence imaging revealed that immature cells, but not more mature CMs, survived for at least one month following injection. These data and comparisons with more mature cells lead us to conclude that immature hypoxia resistant ESC-CMs can be isolated in mass in vitro and, following injection into heart, form grafts that may mediate long-term recovery of global and regional myocardial contractile function following infarction.

Magnetic resonance imaging detects significant sex differences in human myocardial strain

BackgroundThe pathophysiology responsible for the significant outcome disparities between men and women with cardiac disease is largely unknown. Further investigation into basic cardiac physiological differences between the sexes is needed. This study utilized magnetic resonance imaging (MRI)-based multiparametric strain analysis to search for sex-based differences in regional myocardial contractile function.MethodsEnd-systolic strain (circumferential, longitudinal, and radial) was interpolated from MRI-based radiofrequency tissue tagging grid point displacements in each of 60 normal adult volunteers (32 females).ResultsThe average global left ventricular (LV) strain among normal female volunteers (n = 32) was significantly larger in absolute value (functionally better) than in normal male volunteers (n = 28) in both the circumferential direction (Male/Female = -0.19 ± 0.02 vs. -0.21 ± 0.02; p = 0.025) and longitudinal direction (Male/Female = -0.14 ± 0.03 vs. -0.16 ± 0.02; p = 0.007).ConclusionsThe finding of significantly larger circumferential and longitudinal LV strain among normal female volunteers suggests that baseline contractile differences between the sexes may contribute to the well-recognized divergence in cardiovascular disease outcomes. Further work is needed in order to determine the pathologic changes that occur in LV strain between women and men with the onset of cardiovascular disease.

Long-Term Improvement in Postinfarct Left Ventricular Global and Regional Contractile Function Is Mediated by Embryonic Stem Cell–Derived Cardiomyocytes

Pluripotent stem cells represent one promising source for cellular cardiomyoplasty. In this study, we used cardiac magnetic resonance to examine the ability of highly enriched cardiomyocytes (CMs) derived from murine embryonic stem cells (ESC) to form grafts and improve contractile function of infarcted rat hearts. Highly enriched ESC-CMs were obtained by inducing cardiac differentiation of ESCs stably expressing a cardiac-restricted puromycin resistance gene. At the time of transplantation, enriched ESC-CMs expressed cardiac-specific markers and markers of developing CMs, but only 6% of them were proliferating. A growth factor-containing vehicle solution or ESC-CMs (5 to 10 million) suspended in the same solution was injected into athymic rat hearts 1 week after myocardial infarction. Initial infarct size was measured by cardiac magnetic resonance 1 day after myocardial infarction. Compared with vehicle treatment, treatment with ESC-CMs improved global systolic function 1 and 2 months after injection and significantly increased contractile function in initially infarcted areas and border zones. Immunohistochemistry confirmed successful engraftment and the persistence of α-actinin-positive ESC-CMs that also expressed α-smooth muscle actin. Connexin-43-positive sites were observed between grafted ESC-CMs but only rarely between grafted and host CMs. No teratomas were observed in any of the animals. Highly enriched and early-stage ESC-CMs were safe, formed stable grafts, and mediated a long-term recovery of global and regional myocardial contractile function after infarction.

Dobutamine-Induced Improvement in Inferior Myocardial Contractile Function Predicts Reduction in Functional Mitral Regurgitation

Background— Left ventricular (LV) remodeling can increase tethering force to mitral valve and functional mitral regurgitation (FMR). Because the relationship between FMR and regional myocardial function has not been quantitatively evaluated, we conducted a quantitative investigation of this association. Methods and Results— The effective regurgitant orifice (ERO) of FMR in 51 patients with depressed LV ejection fraction (32±9%) secondary to ischemic or nonischemic cardiomyopathy was compared with mitral deformation (valve and annulus), global LV remodeling (volume indices, function, and sphericity), and regional myocardial contractile function, as assessed by longitudinal peak systolic strain rate (Ssr) in LV anterior, anteroseptal, inferoseptal, inferior, inferolateral, and anterolateral segments at rest. Low-dose dobutamine (10 μg/kg per minute)-induced changes in ERO were compared with changes in the variables. Multivariable analysis identified the predictors of ERO at rest as mitral valvular tenting (β=0.062; P &lt;0.001), Ssr in the inferior segment (inferior Ssr) (β=−0.178; P &lt;0.001), and LV sphericity (β=0.414; P =0.001) and the predictors of valvular tenting at rest as inferior Ssr (β=−1.680; P &lt;0.001), LV end-systolic volume index (β=0.022; P =0.001), and LV sphericity (β=3.886; P =0.012). Furthermore, dobutamine-induced reduction in ERO was predicted by reduction in valvular tenting (β=0.087; P &lt;0.001) and increase in inferior Ssr (β=−0.082; P &lt;0.001), and dobutamine-induced reduction in valvular tenting was predicted by increase in inferior Ssr (β=−0.860; P &lt;0.001). Conclusions— Inferior regional myocardial dysfunction was quantitatively associated with mitral valvular tenting and FMR. Moreover, improvement with dobutamine of inferior myocardial contractile function attenuated valvular tenting and FMR. Inferior myocardial contractile function can affect the configuration of the mitral apparatus and predict FMR severity.

Regional myocardial contractile function: multiparametric strain mapping☆

Magnetic resonance imaging (MRI) with tissue tagging enables the quantification of multiple strain indices that can be combined through normalization into a single multiparametric index of regional myocardial contractile function. The aim of this study was to test the ability of multiparametric strain analysis to quantify regional differences in contractile function in an ovine model of myocardial injury. Regional variance in myocardial contractile function was induced in eight sheep by the ligation of the blood supply to the anterior and apical left ventricular (LV) myocardial walls. LV systolic strain was obtained from tissue tagged MRI images. A normal strain database (n=50) defines all parameters of systolic strain and allows normalization of regional function at 15,300 LV points by calculation of a z-score. Multiparametric systolic strain z-scores were therefore determined for 15,300 points in each injured sheep left ventricle. Multiparametric z-scores were found to vary significantly by region (P<0.001). z-Scores in regions remote to the infarct were found to be significantly smaller than those in the regions most likely to include infarcted myocardium. In this pre-clinical evaluation of MRI-based multiparametric strain analysis, it accurately quantified and visually defined regional differences in myocardial contractile function.

Do reconstruction filters really effect the volume and ejection fraction calculation with 99m Tc-sestamibi-gated myocardial SPECT?

Background:ECG -gated myocardial perfusion imaging is a sensitive test for diagnosis of ischemia as well as scarred myocardium. It provides additional information on global and regional myocardial contractile function. A number of methods are available to calculate left ventricular volumes and ejection fractions, which depends on various technical and patients specific factor.Objective:This study was carried out to measure effect of reconstruction filter in calculations of left ventricularend diastolic volume (EDV) and end systolic volume (ESV) and left ventricular ejection fraction (LVEF) from 99mTc-sestamibi myocardial perfusion imaging.Materials and Methods:99mTc-sestamibi-gated SPECT myocardial perfusion imaging was performed in 90 patients. Studies were reconstructed with Butterworth and Metz filters.Results:Mean ejection fraction with Butterworth and Metz filter are 64.3 and 64.2, respectively. Mean EDV is for Butterworth and Metz filters are 77.3 and 78.5 ml, respectively. While ESV was 36.49 and 36.63 ml, stroke volume calculated was 41.54 and 42 ml for Butterworth and Metz filters, respectively. Pearsons’s correlation coefficients between results calculated with Metz and Butterworth filters were 0.994 for ESV, 0.996 for EDV, 0.966 for LVEF and 0.925 for SV. Student ‘t’ test was applied on the data and no significant difference was noted between parameter estimated by Butterworth or Metz filter.Conclusion:This study shows that difference of filter application has no significant effect in computing left ventricular function parameters.

Heart rate in the pathophysiology of coronary blood flow and myocardial ischaemia: benefit from selective bradycardic agents

Starting out from a brief description of the determinants of coronary blood flow (perfusion, pressure, extravascular compression, autoregulation, metabolic regulation, endothelium-mediated regulation and neurohumoral regulation) the present review highlights the overwhelming importance of metabolic regulation such that coronary blood flow is increased at increased heart rate under physiological circumstances and the overwhelming importance of extravascular compression such that coronary blood flow is decreased at increased heart rate through reduction of diastolic duration in the presence of severe coronary stenoses. The review goes on to characterize the role of heart rate in the redistribution of regional myocardial blood flow between a normal coronary vascular tree with preserved autoregulation and a poststenotic vasculature with exhausted coronary reserve. When flow is normalized by heart rate, there is a consistent close relationship of regional myocardial blood flow and contractile function for each single cardiac cycle no matter whether or not there is a coronary stenosis and what the actual blood flow is. beta-Blockade improves both flow and function along this relationship. When the heart rate reduction associated with beta-blockade is prevented by pacing, alpha-adrenergic coronary vasoconstriction is unmasked and both flow and function are deteriorated. Selective heart rate reduction, however, improves both flow and function without any residual negative effect such as unmasked alpha-adrenergic coronary vasoconstriction or negative inotropic action.

Relationships between regional myocardial wall stress and bioenergetics in hearts with left ventricular hypertrophy

This study utilized porcine models of postinfarction left ventricular (LV) remodeling [myocardial infarction (MI); n = 8] and concentric LV hypertrophy secondary to aortic banding (AoB; n = 8) to examine the relationships between regional myocardial contractile function (tagged MRI), wall stress (MRI and LV pressure), and bioenergetics ((31)P-magnetic resonance spectroscopy). Physiological assessments were conducted at a 4-wk time point after MI or AoB surgery. Comparisons were made with size-matched normal animals (normal; n = 8). Both MI and AoB instigated significant LV hypertrophy. Ejection fraction was not significantly altered in the AoB group, but significantly decreased in the MI group (P < 0.01 vs. normal and AoB). Systolic and diastolic wall stresses were approximately two times greater than normal in the infarct region and border zone. Wall stress in the AoB group was not significantly different from that in normal hearts. The infarct border zone demonstrated profound bioenergetic abnormalities, especially in the subendocardium, where the ratio of PCr/ATP decreased from 1.98 +/- 0.16 (normal) to 1.06 +/- 0.30 (MI; P < 0.01). The systolic radial thickening fraction and the circumferential shortening fraction in the anterior wall were severely reduced (MI, P < 0.01 vs. normal). The radial thickening fraction and circumferential shortening fraction in the AoB group were not significantly different from normal. The severely elevated wall stress in the infarct border zone was associated with a significant increase in chemical energy demand and abnormal myocardial energy metabolism. Such severe metabolic perturbations cannot support normal cardiac function, which may explain the observed regional contractile abnormalities in the infarct border zone.

The role of heart rate and the benefits of heart rate reduction in acute myocardial ischaemia

In myocardial ischaemia, detailed analyses of experimental data show that regional myocardial blood flow and contractile function are reduced proportionately—this being contrary to the common notion that the underlying pathological mechanism is a supply/ demand imbalance. Such perfusion–contraction matching is maintained at an increased heart rate. In the normal myocardium, metabolic regulation prevails and tachycardia results in an increased coronary blood flow. In post-stenotic myocardium that has an exhausted dilator reserve, a reduction in diastolic duration prevails, and coronary blood flow is decreased with tachycardia. In the presence of collaterals, both metabolic vasodilation of the normal microcirculation and reduced diastolic duration act in concert to decrease collateral perfusion pressure and collateral flow into the post-stenotic coronary microcirculation. Tachycardia results from sympathetic activation and activation of beta-adrenoceptors. Accordingly, beta-adrenergic blockers have been used to treat patients with stress-induced myocardial ischaemia. The benefits of heart rate reduction by beta-blockade are in part counterbalanced by unmasked alpha-adrenergic coronary vasoconstriction. Selective heart rate-reducing agents can decrease heart rate without unmasking alpha-adrenergic coronary vasoconstriction. They improve the blood flow distribution into the ischaemic myocardium and, as a consequence, improve regional myocardial function. Ivabradine is the only clinically available selective heart rate-reducing agent, and it exerts anti-ischaemic actions in patients with chronic stable angina.

Does Myocardial Fibrosis Hinder Contractile Function and Perfusion in Idiopathic Dilated Cardiomyopathy? PET and MR Imaging Study

To prospectively evaluate, by using positron emission tomography (PET) and magnetic resonance (MR) imaging, the interrelationships between regional myocardial fibrosis, perfusion, and contractile function in patients with idiopathic dilated cardiomyopathy (DCM). The study protocol was approved by the hospital ethics committee, and all subjects gave written informed consent. Sixteen patients with idiopathic DCM (mean age, 54 years +/- 11 [standard deviation]; nine men) and six healthy control subjects (mean age, 28 years +/- 2; five men) were examined with PET and MR tissue tagging. Oxygen 15-labeled water and carbon monoxide were used as tracers at PET to assess myocardial blood flow (MBF) and the perfusable tissue index (PTI), which is inversely related to fibrosis. MBF was determined at rest and during pharmacologically induced hyperemia. Maximum circumferential shortening (E(cc)) was determined with MR tissue tagging. Student t tests were performed for comparison of data sets, and linear regression was used to investigate the association between parameters. Mean global hyperemic MBF (2.23 mL/min/mL +/- 0.73), E(cc) (-10.5% +/- 2.9), and PTI (0.95 +/- 0.10) were lower in the patients with DCM than in the control subjects (4.33 mL/min/mL +/- 0.85, -17.4% +/- 0.6, and 1.09 +/- 0.12, respectively; P < .05 for all). In the patients with DCM, regional PTI was related to E(cc) (r = -0.21, P = .009) but not to resting or hyperemic MBF. Furthermore, regional E(cc) was correlated to both resting (r = -0.28, P = .004) and hyperemic MBF (r = -0.29, P < .001). In addition, the ratio of left ventricular end-diastolic volume to mass, as a reflection of wall stress, was related to global hyperemic MBF (r = -0.52, P = .047) and to global E(cc) (r = 0.69, P = .003). In idiopathic DCM, the extent of myocardial fibrosis is related to the impairment in contractile function, whereas fibrosis and perfusion do not seem to be interrelated. The degree of impairment of hyperemic myocardial perfusion is related to contractility and end-diastolic wall stress.

Assessment of myocardial function of the systemic right ventricle in patients with D-transposition of the great arteries after atrial switch operation by tissue Doppler echocardiography

The long-term follow-up of patients with D-transposition of the great arteries after atrial switch operation shows specific problems such as tricuspid valve insufficiency, rhythm disturbances and failure of the morphologic right ventricle in systemic position. Assessment of the myocardial contractility of the subaortic right ventricle by conventional echocardiography is limited. The usage of tissue Doppler echocardiography with strain combined with strain rate imaging provides a new approach for quantitative analysis of longitudinal myocardial function. The aim of this study was to assess patterns of wall motion and regional contractile function of the systemic right ventricle in patients after atrial switch operation for D-transposition of the great arteries and to compare them to those of normal subjects. Twenty-four patients with Dtransposition of the great arteries after atrial switch operation with a mean age of 21.3 (range, 13 to 31) years and a postoperative period of 16.9 years were examined and compared to 22 control individuals with a mean age of 21.5 (range, 3 to 43) years. Tissue Doppler studies were obtained from apical 4- chamber view to determine regional systolic (Syst(T)) and diastolic (E(T), A(T)) velocities as well as E(T)/A(T) ratio at the basal free wall. The presystolic isovolumic contraction peak was assessed and the ratio of the presystolic peak velocity to the isovolumic acceleration time as the IVA index was calculated. Strain and peak systolic and diastolic strain rates were assessed on basal, middle and apical segments of the right ventricular free wall. Data obtained from the morphologic right systemic ventricle in patients were compared to those derived from the left and the right ventricle in controls. The right ventricular free wall systolic velocities were significantly reduced in patients compared to velocities obtained from the normal right and left ventricle. On the other hand, the IVA index was only reduced in patients compared to the IVA index in the normal subpulmonary right ventricle. Compared to data obtained from the normal systemic left ventricle, the IVA index in patients was not significantly different. In contrast, strain and strain rate parameters in all analyzed segments mostly showed a highly significant reduction compared to normal right and left ventricular data. Tissue Doppler echocardiography is a promising tool for the evaluation of regional myocardial contractile function of the morphologic right systemic ventricle in patients following atrial switch operation for D-transposition of the great arteries. Presystolic, systolic and diastolic regional ventricular function was reduced in the systemic right ventricle. However, further comparative studies using other quantitative parameters of global and regional myocardial function derived from cardiac catheterization or MRI should be performed in order to evaluate the reliability of tissue Doppler echocardiography for the assessment of global right ventricular function in these patients.