Frank Rademakers

Can natural strain and strain rate quantify regional myocardial deformation? A study in healthy subjects

Strain rate (SR) and strain (epsilon) have been proposed as new ultrasound (US) indices for quantifying regional wall deformation, and can be measured from color Doppler myocardial data by determining the local spatial velocity gradient. The aim of this study was to define normal regional SR/epsilon values for both radial and longitudinal myocardial deformation. SR/epsilon profiles were obtained from 40 healthy volunteers. For radial deformation, posterior left ventricular (LV) wall SR/epsilon were calculated. For longitudinal, they were determined for basal, mid- and apical segments of the 1. septum; 2. lateral, 3. posterior and 4. anterior LV walls and for the 5. right ventricular (RV) lateral wall. SR/epsilon values describing radial deformation were higher than the corresponding SR/epsilon values obtained for longitudinal deformation. Longitudinal SR/epsilon were homogeneous throughout the septum and all LV walls. This was in contrast to the normal base-apex velocity gradient. The RV segmental SR/epsilon values were higher than those obtained from the corresponding LV wall and inhomogeneous (higher in the apical segments). SR/epsilon imaging appears to be a robust technique for quantifying regional myocardial deformation.

Clinical indications for cardiovascular magnetic resonance (CMR): Consensus Panel report

Cardiovascular magnetic resonance (CMR) is established in clinical practice for the diagnosis and management of diseases of the cardiovascular system. However, current guidelines for when this technique should be employed in clinical practice have not been revised since a Task Force report of 1998. Considerable technical and practice advances have been made in the intervening years and the level of interest from clinicians in this field is at an unprecedented level. Therefore the aim of this report from a Consensus Panel of established experts in the field of CMR is to update these guidelines. As CMR is a multi-disciplinary technique with international interest, the Consensus Panel was composed of European and American cardiologists and radiologists with major input from members with additional established expertise in paediatric cardiology, nuclear cardiology, magnetic resonance physics and spectroscopy, as well as health economics. The Consensus Panel was originated, approved and funded in its activities by the Working Group on CMR of the European Society of Cardiology and the Society for Cardiovascular Magnetic Resonance. The Consensus Panel recommendations are based on evidence compiled from the literature and expert experience. If there is insufficient evidence in the literature, this is indicated in the report but usually no recommen-

Remodeling of T-Tubules and Reduced Synchrony of Ca2+ Release in Myocytes From Chronically Ischemic Myocardium

In ventricular cardiac myocytes, T-tubule density is an important determinant of the synchrony of sarcoplasmic reticulum (SR) Ca2+ release and could be involved in the reduced SR Ca2+ release in ischemic cardiomyopathy. We therefore investigated T-tubule density and properties of SR Ca2+ release in pigs, 6 weeks after inducing severe stenosis of the circumflex coronary artery (91±3%, N=13) with myocardial infarction (8.8±2.0% of total left ventricular mass). Severe dysfunction in the infarct and adjacent myocardium was documented by magnetic resonance and Doppler myocardial velocity imaging. Myocytes isolated from the adjacent myocardium were compared with myocytes from the same region in weight-matched control pigs. T-tubule density quantified from the di-8-ANEPPS (di-8-butyl-amino-naphthyl-ethylene-pyridinium-propyl-sulfonate) sarcolemmal staining was decreased by 27±7% (P<0.05). Synchrony of SR Ca2+ release (confocal line scan images during whole-cell voltage clamp) was reduced in myocardium myocytes. Delayed release (ie, half-maximal [Ca2+]i occurring later than 20 ms) occurred at 35.5±6.4% of the scan line in myocardial infarction versus 22.7±2.5% in control pigs (P<0.05), prolonging the time to peak of the line-averaged [Ca2+]i transient (121±9 versus 102±5 ms in control pigs, P<0.05). Delayed release colocalized with regions of T-tubule rarefaction and could not be suppressed by activation of protein kinase A. The whole-cell averaged [Ca2+]i transient amplitude was reduced, whereas L-type Ca2+ current density was unchanged and SR content was increased, indicating a reduction in the gain of Ca2+-induced Ca2+ release. In conclusion, reduced T-tubule density during ischemic remodeling is associated with reduced synchrony of Ca2+ release and reduced efficiency of coupling Ca2+ influx to Ca2+ release.

Analysis of relaxation in the evaluation of ventricular function of the heart

T HE MANAGEMENT of cardiac diseases has evolved from one of expectant observation to current medical and surgical interventions aimed at preserving or restoring myocardial function. This has led to a search for thorough understanding and evaluation of global and regional left ventricular function during systole and diastole. In the past, major research emphasis had been placed on the analysis of the contraction phase of systole. Only recently, our attention has been drawn also to the relaxation phase of systole and to diastole. In this respect, early detection of impaired relaxation has been emphasized for the evaluation of both global and regional ventricular function in patients with heart disease. Although early relaxation abnormalities have been found in various cardiac diseases that eventually lead to cardiac failure, such as hypertrophic and ischemic cardiomyopathy, the underlying mechanisms are as yet not fully understood.’ Given the recent progress in our understanding of the physiology and pathophysiology of the relaxation phase of systole of the heart as a muscle and pump,* these mechanisms can now be more easily appreciated. In this review, we will first summarize our present knowledge of relaxation of cardiac muscle. More specifically, we will describe how relaxation is controlled by three interacting determinants: (1) load, (2) (in)activation, and (3) nonuniform distribution of load and (in)activation in space and in time, and how this triple control constitutes a logical extension of a similar triple control of performance during contraction (Fig 1). Second, we will examine how this triple control applies to the intact in situ heart as a pump. Third, we will discuss how various factors, acting either alone or in concert, underlie relaxation abnormalities that occur early on in heart disease. Finally, we will critically review various measurements and indices of ventricular relaxation in view of these new concepts.

Strain Rate Imaging Detects Early Cardiac Effects of Pegylated Liposomal Doxorubicin as Adjuvant Therapy in Elderly Patients with Breast Cancer

OBJECTIVE Cardiac toxicity remains an important side effect of anthracyclines. New drug formulations (eg, pegylated liposomal doxorubicin [PL-DOX]) seem to be a successful strategy for reducing it. Changes in cardiac function induced by early chemotherapy, however, are subtle and difficult to quantitate by conventional imaging methods. Doppler myocardial imaging-based velocity, strain, and strain rate measurements have been shown to sensitively quantify abnormalities in cardiac function in other settings. DESIGN We evaluated the feasibility and sensitivity of strain rate imaging compared with conventional echocardiography in detecting cardiac effects of PL-DOX therapy in elderly patients with cancer. In a pilot study, we examined 16 elderly women (age 69.8 +/- 3.1 years) with breast cancer receiving 6 cycles of PL-DOX. Conventional and Doppler myocardial imaging echocardiography were obtained at baseline and after 3 and 6 cycles of treatment. Segmental peak systolic longitudinal and radial velocity, strain, and strain rate were measured. RESULTS Left ventricular dimensions, ejection fraction, and systolic myocardial velocity did not change throughout the follow-up. In contrast, a significant reduction in longitudinal and radial strain and strain rate was found after 6 cycles (longitudinal strain -18.8% +/- 2.8% vs -22.7% +/- 2.8%, P < .001 vs baseline and P = .001 vs after 3 cycles; radial strain 32.3% +/- 8.1% vs 50.1% +/- 11.6%, P < .001 vs baseline). Changes in radial function appeared earlier and were more pronounced than in longitudinal direction. CONCLUSION In contrast with conventional echocardiography and myocardial velocity measurements, myocardial deformation parameters allowed detecting subtle changes in longitudinal and radial left ventricular function after 6 cycles of PL-DOX. We suggest that Doppler-based myocardial deformation imaging should be used for cardiac function monitoring during chemotherapy.

Remote Myocardial Dysfunction After Acute Anterior Myocardial Infarction: Impact of Left Ventricular Shape on Regional Function A Magnetic Resonance Myocardial Tagging Study

OBJECTIVES We sought to evaluate regional morphology and function in patients in their first week after having a reperfused anterior myocardial infarction (MI) using magnetic resonance (MR) myocardial tagging. BACKGROUND The mechanism of myocardial dysfunction in the remote, noninfarct-related regions is an unresolved issue to date. METHODS Sixteen patients with a first reperfused transmural anterior MI were studied with MR tagging at 5 +/- 2 days after the event, and the results were compared with those of an age-matched control group regions. The left ventricle (LV) was divided into infarct, adjacent and remote regions. Magnetic resonance tagging provided information on the regional ventricular morphology and function. RESULTS Morphologically, an increase of the circumferential radius of curvature was found in the remote myocardium, whereas the longitudinal radius of curvature was increased in all regions of the LV. A significant increase in apical sphericity was also found. A significant reduction in strain and function was found not only in the infarct region, but also in the adjacent and remote myocardium. The loss in regional ejection fraction in the remote myocardium (61.4 +/- 11.7% in patients vs. 68.7 +/- 10.0% in control subjects, p < 0.0001) was related to a significant reduction of the longitudinal and circumferential strain, whereas systolic wall thickening was preserved. CONCLUSIONS Remote myocardial dysfunction contributes significantly to the loss in global ventricular function. This could be secondary to morphologic changes in the infarct region, leading to an increased systolic longitudinal wall stress without loss of intrinsic contractility in the remote regions.

Deformation imaging describes right ventricular function better than longitudinal displacement of the tricuspid ring

Aims To quantify right ventricular (RV) function in patients with chronic thromboembolic pulmonary hypertension (CTEPH) before and after pulmonary endarterectomy (PEA). Methods Out of 33 patients, 16 were evaluated clinically and with echocardiography (conventional and myocardial deformation parameters) before PEA (preop) and at 1 week, 1 month, 3 months and 6 months after PEA. RV fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE) as well as mid-apical and basal peak ejection strain (S) and strain rate (SR) of the RV free wall were measured. Left ventricular (LV) apical lateral wall motion was regarded as indicating changes in overall heart rocking motion (RM). Heart catheterisation was performed before, within 1 week and at 6 months after PEA. Results Clinical and haemodynamic parameters improved significantly after PEA. This correlated with the improvement in RVFAC, S and SR. TAPSE, on the other hand, showed a biphasic response (14.5 (4) mm preop, 8.5 (2.7) mm at 1 week and 11 (1.5) mm at 6 months). Changes in LV apical motion explain this finding. At baseline, TAPSE was enhanced by rocking motion of the heart as a result of the failing RV. Unloading the RV by PEA normalised the rocking motion and TAPSE decreased. Conclusions RV function of CTEPH patients improves steadily after PEA. Unlike S, SR and RVFAC, this is not reflected by TAPSE because of postoperative changes in overall heart motion. Motion independent deformation parameters (S, SR) appear superior in the accurate description of regional RV function

Functional Recovery of Subepicardial Myocardial Tissue in Transmural Myocardial Infarction After Successful Reperfusion: An Important Contribution to the Improvement of Regional and Global Left Ventricular Function

BACKGROUND The transmural extent of myocardial necrosis after an acute coronary artery occlusion can vary considerably. The contribution of residual subepicardial viable myocardium to global left ventricular function is largely unknown. METHODS AND RESULTS We studied 12 patients with single-vessel disease 1 week after successful reperfusion of a first transmural anterior myocardial infarction (MI). With PET, myocardial blood flow (MBF) and glucose metabolism were measured regionally, and the viability was graded as normal, mismatch, or match with severely (<50% of normal) or intermediately (50% to 80% of normal) impaired MBF. Magnetic resonance tagging was used to regionally quantify fiber strains, wall thickening, and ejection fraction in patients 1 week and 3 months after the MI and in age-matched healthy volunteers. From 1 week to 3 months, subepicardial fiber shortening improved significantly in the match region (MBF <50%, -5.1+/-7.0% to -9.9+/-8. 7%; MBF of 50% to 80%, -7.1+/-7.6% to -14.9+/-7.9%). This was associated with an improvement in regional ejection fraction in the infarcted myocardium (29.6+/-21.8% to 43.5+/-15.5%, P<0.0001) and in normal regions (54.3+/-15.1% to 56.5+/-13.1%, P=0.013), contributing to an increase in global ejection fraction from 44.2+/-22.2% to 49. 3+/-17.9% (P<0.0001). CONCLUSIONS Functional recovery of viable subepicardial regions is a mechanism of late improvement in regional and global ejection fraction after a so-called transmural MI.

Morphological and Functional Adaptation of the Maternal Heart during Pregnancy

Background— Pregnancy provides a unique model to study the adaptation of the heart in a physiological situation of transient load changes. The aim of this study was to assess the performance of the left ventricle (LV) in normal, uncomplicated pregnancies while considering the actual LV load and shape. Methods and Results— Serial echocardiographic examinations were performed in 51 women in each pregnancy trimester and 3 to 6 months after delivery. Data from 10 nulliparous, age-matched women were used as the control. Conventional parameters of LV function (ejection fraction) as well as myocardial deformation (strain) were interpreted, taking into consideration maternal hemodynamics and LV shape. Cardiac output increased during pregnancy because of a higher stroke volume in early pregnancy and a late increase in heart rate, whereas total vascular resistance decreased. Progressive development of eccentric hypertrophy was observed, which subsequently recovered postpartum. Sphericity index decreased from the first to the third trimester (1.92±0.17 versus 1.71±0.17) and returned postpartum to values comparable to the control. Although higher LV stroke work was noted toward the third trimester (5.9±1.1 versus 5.3±1.0 Newton meter, P<0.001), ejection fraction showed no significant changes. LV strain decreased significantly in late pregnancy (−19.5±2% to −17.6±1.6%, P<0.001) and returned to baseline values after delivery (−19.5±2%). Conclusions— Pregnancy is a physiological process associated with increased cardiac performance and progressive LV remodeling. These changes are not directly reflected by parameters traditionally considered to describe systolic function, such as ejection fraction and longitudinal deformation. While ejection fraction was insensitive to the functional changes, the transient decrease in longitudinal deformation becomes only plausible when considering the changes in LV geometry.

Left ventricular flow patterns in healthy subjects and patients with prosthetic mitral valves: An in vivo study using echocardiographic particle image velocimetry

OBJECTIVE Echocardiographic particle image velocimetry is a new feature tracking-based approach to visualize and quantify left ventricular flow patterns in vivo. We investigated the potential role of this new technique by assessing vortex formations in healthy left ventricles and the effect of different types of prosthetic valves on intraventricular flow patterns and flow-mediated energy dissipation. METHODS We examined 19 patients (mean age, 57 +/- 19 years; 10 women). Nine were healthy, and 10 had prosthetic mitral valves (5 had bileaflet valves, 4 had bioprostheses, and 1 had a tilting-disc valve). Boluses of left heart contrast were administered intravenously. Echocardiographic apical views were analyzed offline by using prototype software that allowed intracavitary flow to be explored and enabled calculations of energy dissipation (relative pulsatile vorticity strength and vortex pulsation correlation) by means of particle image velocimetry. RESULTS In healthy hearts a vortex filling the entire ventricle stores the kinetic energy of the blood and smoothly redirects the blood to the outflow tract. In patients with prosthetic valves, completely different flow patterns were identified depending on the type, orientation, and position of the valves, as well as left ventricular geometry. Patients with prosthetic valves showed significantly higher left ventricular energy dissipation than healthy subjects (relative pulsatile vorticity strength, 2.4 +/- 0.7 vs 1.6 +/- 0.4 [P < .001]; vortex pulsation correlation, 1.2 +/- 0.5 vs 0.7 +/- 0.2 [P < .001]). CONCLUSIONS Echocardiographic particle image velocimetry is feasible. It clearly distinguishes flow patterns in healthy hearts from those in hearts with different types of prosthetic valves. Echocardiographic particle image velocimetry offers new insights into cardiac function and might be of importance to optimize valve replacement therapy.