Myocardial Layers Research Articles

Transmural differences in respiratory capacity across the rat left ventricle in health, aging, and streptozotocin-induced diabetes mellitus: evidence that mitochondrial dysfunction begins in the subepicardium

In diabetic cardiomyopathy, ventricular dysfunction occurs in the absence of hypertension or atherosclerosis and is accompanied by altered myocardial substrate utilization and depressed mitochondrial respiration. It is not known if mitochondrial function differs across the left ventricular (LV) wall in diabetes. In the healthy heart, the inner subendocardial region demonstrates higher rates of blood flow, oxygen consumption, and ATP turnover compared with the outer subepicardial region, but published transmural respirometric measurements have not demonstrated differences. We aim to measure mitochondrial function in Wistar rat LV to determine the effects of age, streptozotocin-diabetes, and LV layer. High-resolution respirometry measured indexes of respiration in saponin-skinned fibers dissected from the LV subendocardium and subepicardium of 3-mo-old rats after 1 mo of streptozotocin-induced diabetes and 4-mo-old rats following 2 mo of diabetes. Heart rate and heartbeat duration were measured under isoflurane-anesthesia using a fetal-Doppler, and transmission electron microscopy was employed to observe ultrastructural differences. Heart rate decreased with age and diabetes, whereas heartbeat duration increased with diabetes. While there were no transmural respirational differences in young healthy rat hearts, both myocardial layers showed a respiratory depression with age (30-40%). In 1-mo diabetic rat hearts only subepicardial respiration was depressed, whereas after 2 mo diabetes, respiration in subendocardial and subepicardial layers was depressed and showed elevated leak (state 2) respiration. These data provide evidence that mitochondrial dysfunction is first detectable in the subepicardium of diabetic rat LV, whereas there are measureable changes in LV mitochondria after only 4 mo of aging.

The curse of the sympathetic nervous system: are men or women more unfortunate?

The curse of the sympathetic nervous system: are men or women more unfortunate?

Cardiac origin of smooth muscle cells in the inflow tract

Multipotent Isl1+ heart progenitors give rise to three major cardiovascular cell types: cardiac, smooth muscle, and endothelial cells, and play a pivotal role in lineage diversification during cardiogenesis. A critical question is pinpointing when this cardiac–vascular lineage decision is made, and how this plasticity serves to coordinate cardiac chamber and vessel growth. The posterior domain of the Isl1-positive second heart field contributes to the SLN-positive atrial myocardium and myocardial sleeves in the cardiac inflow tract, where myocardial and vascular smooth muscle layers form anatomical and functional continuity. Herein, using a new atrial specific SLN-Cre knockin mouse line, we report that bipotent Isl1+/SLN+ transient cell population contributes to cardiac as well as smooth muscle cells at the heart-vessel junction in cardiac inflow tract. The Isl1+/SLN+ cells are capable of giving rise to cardiac and smooth muscle cells until late gestational stages. These data suggest that the cardiac and smooth muscle cells in the cardiac inflow tract share a common developmental origin. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited".

Probing Field-Induced Tissue Polarization Using Transillumination Fluorescent Imaging

Despite major successes of biophysical theories in predicting the effects of electrical shocks within the heart, recent optical mapping studies have revealed two major discrepancies between theory and experiment: 1), the presence of negative bulk polarization recorded during strong shocks; and 2), the unexpectedly small surface polarization under shock electrodes. There is little consensus as to whether these differences result from deficiencies of experimental techniques, artifacts of tissue damage, or deficiencies of existing theories. Here, we take advantage of recently developed near-infrared voltage-sensitive dyes and transillumination optical imaging to perform, for the first time that we know of, noninvasive probing of field effects deep inside the intact ventricular wall. This technique removes some of the limitations encountered in previous experimental studies. We explicitly demonstrate that deep inside intact myocardial tissue preparations, strong electrical shocks do produce considerable negative bulk polarization previously inferred from surface recordings. We also demonstrate that near-threshold diastolic field stimulation produces activation of deep myocardial layers 2–6 mm away from the cathodal surface, contrary to theory. Using bidomain simulations we explore factors that may improve the agreement between theory and experiment. We show that the inclusion of negative asymmetric current can qualitatively explain negative bulk polarization in a discontinuous bidomain model.

Morphological and Molecular Analysis of Angiogenesis after Intramyocardial Transplantation of Autologous Bone Marrow Mononuclear Cells

We studied the peculiarities of angiogenesis in the postinfarction period after transmyocardial laser revascularization and intramyocardial implantation of mononuclear bone marrow cells into the pericicatrical zone of the left ventricular myocardium in dogs. Morphological manifestation of angiogenesis in the myocardium after application of laser and cell technologies are angiomatosis, formation of large thin-wall vessels and sinusoids. The angiogenic effect of implanted mononuclear bone marrow cells is determined by high content (43-47%) of CD31+ cells in both adherent and nonadherent fractions. More pronounced angiogenic potential of nonadherent cells is determined by intensive expression of cytokine VEGF-B and D mRNA essential for arterial vessels growth. Immunohistochemical studies showed that about 90% cells of the nonadherent fraction are endothelial precursors expressing endothelial cell markers isolectin B4 and VEGF-R2. It was found that the use of adherent mononuclear bone marrow cells during the postinfarction period induces ossification of the epicardium and subepicardial myocardium layer, formation of cartilage plates, and focal calcification. Implantation of nonadherent mononuclear bone marrow cells into transmyocardial laser channels did not induce ectopic ossification of the myocardium.

Acute amiodarone promotes drift and early termination of spiral wave re-entry

Intravenous application of amiodarone is commonly used in the treatment of life-threatening arrhythmias, but the underlying mechanism is not fully understood. The purpose of the present study is to investigate the acute effects of amiodarone on spiral wave (SW) re-entry, the primary organization machinery of ventricular tachycardia/fibrillation (VT/VF), in comparison with lidocaine. A two-dimensional ventricular myocardial layer was obtained from 24 Langendorff-perfused rabbit hearts, and epicardial excitations were analyzed by high-resolution optical mapping. During basic stimulation, amiodarone (5 microM) caused prolongation of action potential duration (APD) by 5.6%-9.1%, whereas lidocaine (15 microM) caused APD shortening by 5.0%-6.4%. Amiodarone and lidocaine reduced conduction velocity similarly. Ventricular tachycardias induced by DC stimulation in the presence of amiodarone were of shorter duration (sustained-VTs >30 s/total VTs: 2/58, amiodarone vs 13/52, control), whereas those with lidocaine were of longer duration (22/73, lidocaine vs 14/58, control). Amiodarone caused prolongation of VT cycle length and destabilization of SW re-entry, which is characterized by marked prolongation of functional block lines, frequent wavefront-tail interactions near the rotation center, and considerable drift, leading to its early annihilation via collision with anatomical boundaries. Spiral wave re-entry in the presence of lidocaine was more stabilized than in control. In the anisotropic ventricular myocardium, amiodarone destabilizes SW re-entry facilitating its early termination. Lidocaine, in contrast, stabilizes SW re-entry resulting in its persistence.

Fortuitous Discovery of Partial Uhl Anomaly in a Male Adult

We report the case of a 44-year-old man referred to our institution for suspicion of arrhythmogenic right ventricular (RV) cardiomyopathy. Both familial and personal medical histories were unremarkable, except the notion of a slight unexplored heart murmur during childhood. He decided to undergo a “40s” medical checkup. On presentation to the general practitioner, he had described a slight fatigue for 8 months without concomitant stress. Physical examination revealed no abnormality. ECG showed a type I atrioventricular block and a complete right bundle-branch block (Figure 1A). Transthoracic echocardiography showed an unusual left ventricle (LV) with a leftward curveted interventricular septum (IVS) and preserved global and segmental LV systolic function, suggestive of high systolic RV pressure or takotsubo cardiomyopathy (Figure 1B and Movie I in the online-only Data Supplement). However further analysis showed normal systolic pulmonary artery pressure and LV filling pressures. The apical 4-chamber view showed an abnormal RV with an aneurysm-like shape of the basal lateral free wall (Figure 1B and Movie II in the online-only Data Supplement) but with normal kinetics. A first cardiac magnetic resonance image showed biventricular abnormalities, particularly focused on RV wall motion, which justified additional morphological investigations. No abnormal pulmonary venous return was noticed. Invasive coronary angiogram was normal. The patient was later referred to our unit by his attending cardiologist and underwent invasive hemodynamics and biventricular contrast angiography. Cardiac index (pulmonary artery thermodilution) and biventricular volumes were normal. Blood gas content analysis disclosed an intracardiac shunt. RV angiography (Figure 2A and 2B) showed a truncated RV apex and the absence of trabeculations in the anteroapical and inferoapical zones, therefore characterized by a smooth …

Tyrosine hydroxylase is expressed during early heart development and is required for cardiac chamber formation

Tyrosine hydroxylase (TH) is the first and rate-limiting enzyme in catecholamine biosynthesis. Whereas the neuroendocrine roles of cathecolamines postnatally are well known, the presence and function of TH in organogenesis is unclear. The aim of this study was to define the expression of TH during cardiac development and to unravel the role it may play in heart formation. We studied TH expression in chick embryos by whole mount in situ hybridization and by quantitative reverse transcription-polymerase chain reaction and analysed TH activity by high-performance liquid chromatography. We used gain- and loss-of-function models to characterize the role of TH in early cardiogenesis. We found that TH expression was enriched in the cardiac field of gastrulating chick embryos. By stage 8, TH mRNA was restricted to the splanchnic mesoderm of both endocardial tubes and was subsequently expressed predominantly in the myocardial layer of the atrial segment. Overexpression of TH led to increased atrial myosin heavy chain (AMHC1) and T-box 5 gene (Tbx5) expression in the ventricular region and induced bradyarrhythmia. Similarly, addition of l-3,4-dihydroxyphenylalanine (l-DOPA) or dopamine induced ectopic expression of cardiac transcription factors (cNkx2.5, Tbx5) and AMHC1 as well as sarcomere formation. Conversely, blockage of dopamine biosynthesis and loss of TH activity decreased AMHC1 and Tbx5 expression, whereas exposure to retinoic acid (RA) induced TH expression in parallel to that of AMHC1 and Tbx5. Concordantly, inhibition of endogenous RA synthesis decreased TH expression as well as that of AMHC1 and Tbx5. TH is expressed in a dynamic pattern during the primitive heart tube formation. TH induces cardiac differentiation in vivo and it is a key regulator of the heart patterning, conferring atriogenic identity.

Utility of Real-Time 3-Dimensional Echocardiography and Magnetic Resonance Imaging for Evaluation of Danon Disease

A 21-year-old man was admitted to the hospital with exertional dyspnea. At the age of 14, he was diagnosed with Danon disease by genetic analysis (a 2–base-pair deletion at positions 288 and 289 in exon 3 was identified in the lysosome-associated membrane protein-2 [LAMP2] gene of the patient, which led to a frameshift and resulted in a premature stop codon). A chest radiograph demonstrated moderate cardiomegaly (cardiothoracic ratio of 58%). The ECG exhibited normal sinus rhythm, wide and bifid P waves with a duration of 170 ms, complete left bundle-branch block with a QRS duration of 200 ms, and a leftward axis (−2°; Figure 1). Figure 1. Twelve-lead ECGs. Echocardiography revealed left ventricular (LV) dilatation with an end-diastolic internal dimension of 60 mm and diffusely hypokinetic LV wall motion with fractional shortening of 8% (Figure 2; Movie I of the online-only Data Supplement). …

Anatomy of the python heart

The hearts of all snakes and lizards consist of two atria and a single incompletely divided ventricle. In general, the squamate ventricle is subdivided into three chambers: cavum arteriosum (left), cavum venosum (medial) and cavum pulmonale (right). Although a similar division also applies to the heart of pythons, this family of snakes is unique amongst snakes in having intracardiac pressure separation. Here we provide a detailed anatomical description of the cardiac structures that confer this functional division. We measured the masses and volumes of the ventricular chambers, and we describe the gross morphology based on dissections of the heart from 13 ball pythons (Python regius) and one Burmese python (P. molurus). The cavum venosum is much reduced in pythons and constitutes approximately 10% of the cavum arteriosum. We suggest that shunts will always be less than 20%, while other studies conclude up to 50%. The high-pressure cavum arteriosum accounted for approximately 75% of the total ventricular mass, and was twice as dense as the low-pressure cavum pulmonale. The reptile ventricle has a core of spongious myocardium, but the three ventricular septa that separate the pulmonary and systemic chambers--the muscular ridge, the bulbuslamelle and the vertical septum--all had layers of compact myocardium. Pythons, however, have unique pads of connective tissue on the site of pressure separation. Because the hearts of varanid lizards, which also are endowed with pressure separation, share many of these morphological specializations, we propose that intraventricular compact myocardium is an indicator of high-pressure systems and possibly pressure separation.

The p75 neurotrophin receptor, semaphorins, and sympathetic traffic in the heart

the sympathetic and parasympathetic branches of the autonomic nervous system control cardiac function through the coordinated activity generated by neurons within the intracardiac autonomic ganglia and central nervous system (3). Activation of the sympathetic efferent projections to the heart increases heart rate, modifies the pattern and conduction velocity of the impulse through the heart, and augments both atrial and ventricular contractility while hastening myocardial relaxation. In the vasculature, the sympathetic nervous system (SNS) reduces venous capacitance and constricts resistance vessels, increasing blood pressure. Conversely, the parasympathetic nervous system (PSNS) decreases heart rate and cardiac impulse conduction. More recent evidence has suggested that the PSNS may also affect ventricular function, indirectly by countering β-adrenergic action or directly via inhibition of L-type Ca2+ channels (34). A transient imbalance between these two branches can lead to increased heart rate and blood pressure when cardiac output is increased. When subnormal cardiac PSNS activity concomitant with sympathetic hyperactivation persists, such as after myocardial infarction, this disequilibrium may increase the risk for cardiac adverse events, including arrhythmias, hypertension, cardiac hypertrophy, and, ultimately, heart failure. This condition is called “autonomic neural remodeling” and can greatly contribute to the induction of ventricular fibrillation, thus increasing the patient's susceptibility to sudden cardiac death (41, 47). It is plausible that neurotrophic factors, target organ-secreted proteins essential for the development and differentiation of neurons, are involved in the remarkable neuroplasticity exhibited by the SNS in the adult life, including autonomic remodeling after infarction and/or in the onset and progression of congestive heart failure (17, 30, 32).

M Cells in the Human Heart

See related articles, pages 981–991 Dispersion of repolarization across the ventricular wall has been suggested to underlie the inscription of the normal electrocardiographic T wave and when amplified to contribute prominently to the development of cardiac arrhythmias.1–3 The magnitude of transmural dispersion of repolarization (TDR) is attributable to intrinsic differences in the action potential duration (APD) of the 3 principal cell types that comprise the ventricular myocardium and the extent to which these repolarization differences are damped by electrotonic forces. An increase in tissue resistivity in the deep subepicardium,4 attributable to a sharp transition in cell orientation,3 reduced expression of connexin 435,6 and increased density of collagen7 in this region, contributes to the expression of repolarization heterogeneities across the ventricular wall by limiting the degree of electrotonic interaction between the myocardial layers. Thus, the degree of electrotonic coupling, together with the intrinsic differences in APD, determines the extent to which TDR is expressed and its impact on arrhythmogenesis, as well as on the morphology of the T wave. It is noteworthy that even in the absence of any difference in final repolarization time, electrotonic forces generated by transmural differences in the shape of the action potential can inscribe an upright T wave in the ECG. Theoretical studies have also been helpful in our understanding of the role of electrical coupling in the expression of TDR.8 TDR is in large part attributable to the presence of M cells between the endocardial and epicardial layers of the heart. The M cell, discovered in the early 1990s and named in memory of Gordon K. Moe,9,10 has as its hallmark the ability to prolong its action potential more than that of normal epicardium or endocardium in response to a slowing of rate or exposure to agents …

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

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. 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. 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. 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.

Effect of Vascular Cadherin Knockdown on Zebrafish Vasculature during Development

BackgroundVascular endothelial cadherin (VE-cad) is essential for endothelial barrier integrity and vascular sprouting. However, the role of this important protein in cardiovascular development is only recently becoming apparent.Methodology/Principal FindingsTo characterize the role of VE-cadherin in cardiovascular development, we analyzed cardiovascular development in a zebrafish VE-cad knockdown model. Embryos deficient in VE-cad show profoundly impaired cardiac development despite having apparently normal peripheral vasculature. Initial formation of the heart proceeds normally in knockdown embryos, but subsequent looping morphogenesis is impaired. Consistent with these results, VE-cad knockdown embryos demonstrate impaired cardiac function and early circulatory arrest. Histologic examination of knockdown embryos shows persistent, abnormal separation of the endocardial and myocardial layers. Using transmission electron microscopy, we demonstrate that endocardial junctions form poorly in VE-cad knockdown embryos, with resulting leak across the endothelial layer and reduction in the density of the cardiac jelly.ConclusionsOur results demonstrate a significant role for VE-cadherin in cardiac development independent of its effects on the formation of the peripheral vasculature.

Radial deformation by tissue Doppler imaging in multiple myocardial layers

Objectives. Measuring strain in multiple myocardial layers using 2-dimensional tissue Doppler imaging may provide valuable diagnostic information about non-transmural disease. However, its feasibility in humans has not been demonstrated previously, and optimal machine settings not defined. Design. From parasternal short axis, zoomed tissue Doppler imaging of the left ventricular inferior wall was obtained in 23 young, healthy humans. Images were recorded with six different machine settings. Velocity, strain rate and strain were measured in two and three layers across the wall. Result. For two-layer-measurements, all subendocardial values were significantly higher than the subepicardial ones (p<0.003 for all data sets). Minimal radial and maximal lateral averaging resulted in largest strain differences: 106.4±32.6% (mean±SD) subendocardially versus 54.2±20.1% subepicardially. By similar settings in three layers, strain was 105.7±34.5% subendocardially, 81.2±26.9% midmyocardially and 48.3±26.9% subepicardially (p <0.05). Conclusion. We have demonstrated that it is feasible to measure radial velocity, strain rate and strain in up to three individual layers in young healthy humans, and the diagnostic potentials should be tested on patient groups.

Circumferential and Longitudinal Strain in 3 Myocardial Layers in Normal Subjects and in Patients with Regional Left Ventricular Dysfunction

The left ventricle is not homogenous and is composed of 3 myocardial layers. Until recently, magnetic resonance imaging has been the only noninvasive technique for detailed evaluation of the left ventricular (LV) wall. The aim of this study was to analyze strain in 3 myocardial layers using speckle-tracking echocardiography. Twenty normal subjects and 21 patients with LV dysfunction underwent echocardiography. Short-axis (for circumferential) and apical (for longitudinal strain) views were analyzed using modified speckle-tracking software enabling the analysis of strain in 3 myocardial layers. In normal subjects, longitudinal and circumferential strain was highest in the endocardium and lowest in the epicardium. Longitudinal endocardial and mid layer strain was highest in the apex and lowest in the base. Epicardial longitudinal strain was homogenous over the left ventricle. Circumferential 3-layer strain was highest in the apex and lowest in the base. In patients with LV dysfunction, strain was lower, with late diastolic or double peak. Three-layer analysis of circumferential and longitudinal strain using speckle-tracking imaging can be performed on a clinical basis and may become an important method for the assessment of real-time, quantitative global and regional LV function.

Ventricular Angiography Images in Noncompaction of the Left Ventricle

Left ventricular noncompaction, previously known as ‘‘spongy left ventricular myocardium,’’ is a rare, unclassified cardiomyopathy [1, 2]. It is characterized by prominent myocardial trabeculations and deep intertrabecular recesses that lie in continuity with the left ventricle cavity. The echocardiographic diagnostic criteria present the ‘‘gold standard’’ for diagnosis [1, 3]. Rarely this abnormality might be associated with other congenital heart defects, and then angiography is a useful tool. Because of this there are only a few angiographic images of noncompaction of the left ventricle (NCLV) in the literature. Prompt recognition of the disease is mandatory because of its high mortality and morbidity rates in symptomatic patients. Thus, we present here the angiographic images of an infant with such an anomaly. The infant was born normally after an uneventful pregnancy to healthy unrelated parents. The female patient’s birth weight was 2.8 kg. She was admitted at the age of 3 months with signs of severe respiratory distress. A loud systolic murmur of 3/6 intensity was audible at the left sternal border. There were crepitations in her chest as well as hepatomegaly. Chest X-ray showed cardiomegaly (cardiothoracic index 0.63) and plethoric lung fields. Echocardiogram showed perimembranous ventricular septal defect; increased pulmonary pressure; and a hypertrophied, spongiform, poorly contractile left ventricle. The ejection fraction was 38%, and there were intramural recesses communicating with the left ventricle cavity, with blood flowing in and out from the ventricle. A ratio of 2.25:1 was calculated between the thicknesses of the noncompacted and compacted myocardial layers in systole (Figs. 1 and 2). Angiography was performed after the patient was clinically stabilized. Left ventricular angiography (Fig. 3) showed the left ventricle with a wide spongy-like layer and the perimembranous ventricle septal defect. The pressure was increased in the right ventricle (70/0/13 mmHg) and in the pulmonary artery (53/10/30 mmHg). The child was referred for surgical intervention. The ventricular septal defect (VSD) was closed with a 9-mm Dacron patch. The postoperative period was uncomplicated. Because the patient had residual congestive heart failure due to NCLV at 12month follow-up, pharmacotheraphy has been continued up to the present (digitalis, diuretics, and angiotensin-converting enzyme inhibitors).

P22.15: Unguarded tricuspid valvar orifice in a fetus with right ventricular cardiomyodysplasia

The syndrome of unguarded tricuspid valve is uncommon. This cardiac malformation is characterized by the absence of the tricuspid valvular leaflets in the setting of a normal atrioventricular junction and obligatory tricuspid regurgitation. First trimester screening was performed in a gravida IV, para II at 13 weeks of gestation resulting in the documentation of an enlarged nuchal translucency > 95. percentile. At 16 weeks of gestation ultrasound revealed signs of cardiac failure. Amniocentesis for karyotyping, therefore, was performed at 15 + 1 weeks of gestation showing a normal female karyotype, 46 XX. We describe a fetus with grossly dilated ventricle and atrium and with severe tricuspid and pulmonary valvular regurgitation. The tricuspid tissue and valvular apparatus could not be identified. Colour Doppler showed the highly unusual retrograde perfusion of the right heart. The pregnancy was terminated during the 19th gestational week. Necropsy examination confirmed the prenatal suspicion of unguarded tricuspid valve and revealed moderate pulmonar stenosis. While the tricuspid orifice was present, there was neither valvular tissue nor papillary muscles to be found. Moreover, the anomaly was characterized by the local absence of the myocardial layer of the right ventricle with aposition of the epicardium onto the endocardium. The differentiation of this anomaly from other dysplasias of the right atrioventricular junction and right sided myocardium may be difficult. The colour Doppler flow pattern helps in the differentiation of this malformation from Ebstein's anomaly and other tricuspid valve abnormalities.

Effect of changes in left ventricular anatomy and conduction velocity on the QRS voltage and morphology in left ventricular hypertrophy: a model study

The increased QRS voltage is considered to be a specific electrocardiogram (ECG) sign of left ventricular hypertrophy (LVH), and it is expected that the QRS voltage reflects the increase in left ventricular mass (LVM). However, the increased QRS voltage is only one of QRS patterns observed in patients with LVH. According to the solid angle theory, the resultant QRS voltage is influenced not only by spatial (anatomic) but also by nonspatial (electrophysiologic) determinants. In this study, we used a computer model to evaluate the effect of changes in anatomy and conduction velocity of the left ventricle on QRS complex characteristics. Material and Methods The model defines the geometry of cardiac ventricles analytically as parts of ellipsoids and allows to change dimensions of the ventricles, as well as the conduction velocity in the individual layers of myocardium. Three types of anatomic changes were simulated: concentric hypertrophy, eccentric hypertrophy, and dilatation. The conduction velocity was slowed in the inner layer of the left ventricle representing the Purkinje fiber mesh and in the layers representing the working myocardium. The outcomes of the model are presented as the time course of the spatial QRS vector magnitude, the vectorcardiographic QRS loops (VCGs) in horizontal, left sagittal, and frontal planes, as well as derived 12-lead ECGs. The following indicators of the 12-lead ECG were evaluated: the left axis deviation, the intrinsicoid deflection in V6, Cornell voltage, Cornell voltage-duration product, and Sokolow-Lyon index. Results The increase in LVM did not affect the QRS voltage proportionally, and the LVM and type of hypertrophy were not the only determinants of the QRS patterns. The conduction velocity slowing resulted in a spectrum of QRS patterns including increased QRS voltage and duration, left axis deviation, prolonged intrinsicoid deflection, VCG patterns of left bundle branch block, as well as pseudo-normal VCG/ECG patterns. The anatomic changes and conduction velocity slowing affected differently Sokolow-Lyon index and Cornell criteria. Conclusion We showed that the LVM is not the only determinant of the QRS complex changes in LVH, but it is rather a combination of anatomic and electric remodeling that creates the whole spectrum of the QRS complex changes seen in LVH patients. The slowed conduction velocity in the model heart produced QRS patterns consistent with changes described in LVH, even if the LVM was not changed.

A novel multi-layer approach of measuring myocardial strain and torsion by 2D speckle tracking imaging in normal subjects and patients with heart diseases

This study adopted a new multi-layer approach of measuring myocardial deformation by two-dimensional (2D) speckle tracking imaging to examine whether a transmural gradient exists in normal subjects and cardiac diseases. Eighty patients were included with 20 in each group: (1) normal control; (2) acute coronary syndrome (ACS) with ejection fraction (EF) >45%; (3) right ventricular apical (RVA) pacing with EF>45%; (4) systolic heart failure (SHF) with EF<45%. Circumferential strain (ε-circum), torsion (Tor) and systolic dyssynchrony defined as the maximal difference in the time to peak circumferential strain were measured in the subendocardial and subepicardial myocardium layers (QLab 6.0, Philips). In all the 4 groups, a subendocardial to subepicardial gradient was present in both ε-circum (-20.7 ± 7.6 vs. -14.9 ± 5.6%, p<0.001) and Tor (12.0 ± 6.0 vs. 9.3 ± 4.7°, p<0.05), with higher values in the subendocardial layer. However, it was significantly narrowed for ε-circum (2.7 ± 1.2%) and Tor (0.8 ± 0.9°) in SHF patients (all p ≤ 0.001 vs. other groups). On the contrary, systolic dyssynchrony measured in the 2 layers showed no difference (264 ± 107 vs. 273 ± 110 ms, p = NS) and a homogenous distribution in ε-circum was observed from basal to apical planes (-17.0 ± 6.8 vs. -18.1 ± 7.4 vs. -18.1 ± 7.8%, all p = NS). A transmural gradient exists in circumferential strain and torsion, with higher values in the subendocardial layer. It might be reduced when systolic function is impaired. Therefore, the multi-layer approach of 2D speckle tracking imaging provides further information on assessment of myocardial diseases.