Visualization of the intracavitary blood flow in systemic ventricles of Fontan patients by contrast echocardiography using particle image velocimetry

Objectives

Two-dimensional strain echocardiography (2DSE) technique has enabled accurate quantification of regional myocardial function. This experimental study was aimed to investigate the value of 2DSE in detection of segmental regional myocardial dysfunction induced by fibrosis following myocardial infarction in a small animal (rat) model.

Methods

A rat model of myocardial infarction was established by ligation of the proximal left anterior descending coronary artery in 17 SD rats. Regional myocardial function was detected by 2DSE at baseline and 4-weeks post-infarction, including end-systolic radial strain and strain rate (SR and SrR) and end-systolic circumferential strain and strain rate (SC and SrC) of each of six segments at papillary level. According to the size of scar found by histologic Masson staining, the optimal cutoff points of parameters for detecting scar area were analyzed and the sensitivity and specificity of every parameter to detect myocardial scar were obtained using ROC.

Results

(1) Comparing with parameters measured at baseline, there were significant decreases in SR, SrR, SC and SrC of each segment at 4 weeks post-infarction, with the worst in the infarct area (32.90 ± 8.79 vs 11.18 ± 3.89, 6.28 ± 1.35 vs 3.18 ± 0.47, -14.46 ± 2.21 vs -6.30 ± 2.17 and 4.93 ± 0.95 vs 2.59 ± 1.16, respectively) (all P < 0.05). (2)By 4 weeks, the myocardium of infarct area (anteroseptum, anterior and anterolateral) had fibrosis (31.33 ± 9.89, 73.42 ± 13.21 and 13.99 ± 3.24%, respectively) with minimal fibrosis in inferoseptal segment (0.32 ± 0.19%), no fibrosis was found in the inferior and inferolateral segments. (3)Significant negative correlations were found between the size of segmental scar and 2DSE parameters (r-value -0.61 ~ -0.80, all P < 0.01) with the strongest correlation in SR. SR less than 10% has 84% sensitivity and 98% specificity for detecting segments of scar area greater than 30% with AUC = 0.97.

Conclusions

2DSE is able to assess regional myocardial dysfunction in a rat model of myocardial infarction and has high accuracy in detecting infarct segments with scar area greater than 30%.     

Atorvastatin therapy during the peri-infarct period attenuates left ventricular dysfunction and remodeling after myocardial infarction

Although statins impart a number of cardiovascular benefits, whether statin therapy during the peri-infarct period improves subsequent myocardial structure and function remains unclear. Thus, we evaluated the effects of atorvastatin on cardiac function, remodeling, fibrosis, and apoptosis after myocardial infarction (MI). Two groups of rats were subjected to permanent coronary occlusion. Group II (n = 14) received oral atorvastatin (10 mg/kg/d) daily for 3 wk before and 4 wk after MI, while group I (n = 12) received equivalent doses of vehicle. Infarct size (Masson''s trichrome-stained sections) was similar in both groups. Compared with group I, echocardiographic left ventricular ejection fraction (LVEF) and fractional area change (FAC) were higher while LV end-diastolic volume (LVEDV) and LV end-systolic and end-diastolic diameters (LVESD and LVEDD) were lower in treated rats. Hemodynamically, atorvastatin-treated rats exhibited significantly higher dP/dt_max, end-systolic elastance (Ees), and preload recruitable stroke work (PRSW) and lower LV end-diastolic pressure (LVEDP). Morphometrically, infarct wall thickness was greater in treated rats. The improvement of LV function by atorvastatin was associated with a decrease in hydroxyproline content and in the number of apoptotic cardiomyocyte nuclei. We conclude that atorvastatin therapy during the peri-infarct period significantly improves LV function and limits adverse LV remodeling following MI independent of a reduction in infarct size. These salubrious effects may be due in part to a decrease in myocardial fibrosis and apoptosis.     

Left ventricular strain, rotation, and torsion as markers of acute myocardial ischemia

This study investigates how tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE) describe regional myocardial deformation during controlled reductions of left anterior descending (LAD) coronary artery perfusion pressure. In eight anesthetized pigs, a shunt with constrictor was installed from the brachiocephalic artery to the LAD. Data were obtained with open shunt, followed by four degrees of stenosis (S1-S4) of increasing severity: S1, ～15%; S2, ～35%; S3, ～50%; and S4, ～60% reductions of LAD perfusion pressure. At each situation, microspheres for perfusion measurements were injected and left ventricular (LV) short- and long-axis cineloops were recorded. In the anterior wall, radial, circumferential, and longitudinal one-layer STE strain, one-layer radial TDI strain, and three-layer radial TDI and STE strain were measured. LV peak mean rotation was measured at six equidistant levels from apex to base (in 7 pigs). LV torsion was calculated from end-systolic mean rotation. With open shunt, three-layer TDI analysis showed a transmural strain gradient with no perfusion gradient. Perfusion, one-layer TDI strain, and strain in the mid- and subendocardium from three-layer TDI were reduced at S2 (P < 0.05). STE strain was not affected until S3 (P < 0.05). Peak mean rotation, increasing toward the apex, decreased at the three apical levels at S4 (P < 0.05). LV torsion did not decrease (P = 0.26). In conclusion, TDI strain detected dysfunction already with minor changes in global hemodynamics, whereas STE strain was first reduced with moderate changes. LV peak mean rotation was not reduced until severe reduction of LAD perfusion pressure, but remained increasingly counterclockwise toward the apex. LV torsion remained unaffected by ischemia.     

Alarin alleviated cardiac fibrosis via attenuating oxidative stress in heart failure rats

The present study was to explore whether alarin could alleviate heart failure (HF) and attenuate cardia fibrosis via inhibiting oxidative stress. The fibrosis of cardiac fibroblasts (CFs) was induced by angiotensin (Ang) II. HF models were induced by ligation of the left anterior descending artery to cause ischemia myocardial infarction (MI) in Sprague–Dawley rats. Alarin (1.0 nM/kg/d) was administrated by intraperitoneal injection for 28 days. The decreases of left ventricular (LV) ejection fraction (EF), fractional shortening (FS), the maximum of the first differentiation of LV pressure (LV ± dp/dt_max) and LV systolic pressure (LVSP), and the increases of LV volume in systole (LVVS), LV volume in diastole (LVVD), LV end-systolic diameter (LVESD) and LV end-diastolic diameter (LVEDD) in MI rats were improved by alarin treatment. The increases in the expression levels of collagen I, collagen III, and transforming growth factor (TGF)-β were inhibited by alarin treatment in CFs and in the hearts of MI rats. The levels of NADPH oxidase (Nox) activity, superoxide anions and malondialdehyde (MDA) levels were increased, and the level of superoxide dismutase (SOD) activity was reduced in Ang II-treated CFs, which were reversed by alarin. Nox1 overexpression reversed the effects of alarin on attenuating the increases of collagen I, collagen III and TGF-β expression levels induced by Ang II in CFs. These results indicated that alarin improved HF and cardiac fibrosis via inhibiting oxidative stress in HF rats. Nox1 played important roles in the regulation of alarin effects on attenuating CFs fibrosis induced by Ang II.

     

Susceptibility to systolic dysfunction in the myocardium from chronically infarcted spontaneously hypertensive rats

We explored whether the hypertensive heart is susceptible to myocardial dysfunction in viable noninfarcted tissue post-myocardial infarction (MI), the potential mechanisms thereof, and the impact of these changes on pump function. Six to seven months after the ligation of the left anterior descending coronary artery, left ventricular (LV) myocardial systolic function, as assessed from the percent shortening of the noninfarcted lateral wall segmental length determined over a range of filling pressures (ultrasonic transducers placed in the lateral wall in anaesthetized, open-chest, ventilated rats) and the percent thickening of the posterior wall (echocardiography), was reduced in infarcted spontaneous hypertensive rats (SHR-MI) (P < 0.05) but not in normotensive Wistar-Kyoto (WKY-MI) animals compared with corresponding controls [SHR-sham operations (Sham) and WKY-Sham]. This change in the regional myocardial function in SHR-MI, but not in WKY-MI, occurred despite a similar degree of LV dilatation (increased LV end-diastolic dimensions and volume intercept of the LV end-diastolic pressure-volume relation) in SHR-MI and WKY-MI rats and a lack of difference in LV relative wall thinning, LV wall stress, apoptosis [terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling (TUNEL)], or necrosis (pathological score) between SHR-MI and WKY-MI rats. Although the change in regional myocardial function in the SHR-MI group was not associated with a greater reduction in baseline global LV chamber systolic function [end-systolic elastance (LV E(es)) and endocardial fractional shortening determined in the absence of an adrenergic stimulus], in the presence of an isoproterenol challenge, noninfarct-zone LV systolic myocardial dysfunction manifested in a significant reduction in LV E(es) in SHR-MI compared with WKY-MI and SHR and WKY-Sham rats (P < 0.04). In conclusion, these data suggest that with chronic MI, the hypertensive heart is susceptible to the development of myocardial dysfunction, a change that cannot be attributed to excessive chamber dilatation, apoptosis, or necrosis, but which in turn contributes toward a reduced cardiac adrenergic inotropic reserve.     

Preemptive heme oxygenase-1 gene delivery reveals reduced mortality and preservation of left ventricular function 1 yr after acute myocardial infarction

We reported previously that predelivery of heme oxygenase-1 (HO-1) gene to the heart by adeno-associated virus-2 (AAV-2) markedly reduces ischemia and reperfusion (I/R)-induced myocardial injury. However, the effect of preemptive HO-1 gene delivery on long-term survival and prevention of postinfarction heart failure has not been determined. We assessed the effect of HO-1 gene delivery on long-term survival, myocardial function, and left ventricular (LV) remodeling 1 yr after myocardial infarction (MI) using echocardiographic imaging, pressure-volume (PV) analysis, and histomorphometric approaches. Two groups of Lewis rats were injected with 2 x 10(11) particles of AAV-LacZ (control) or AAV-human HO-1 (hHO-1) in the anterior-posterior apical region of the LV wall. Six weeks after gene transfer, animals were subjected to 30 min of ischemia by ligation of the left anterior descending artery followed by reperfusion. Echocardiographic measurements and PV analysis of LV function were obtained at 2 wk and 12 mo after I/R. One year after acute MI, mortality was markedly reduced in the HO-1-treated animals compared with the LacZ-treated animals. PV analysis demonstrated significantly enhanced LV developed pressure, elevated maximal dP/dt, and lower end-diastolic volume in the HO-1 animals compared with the LacZ animals. Echocardiography showed a larger apical anterior-to-posterior wall ratio in HO-1 animals compared with LacZ animals. Morphometric analysis revealed extensive myocardial scarring and fibrosis in the infarcted LV area of LacZ animals, which was reduced by 62% in HO-1 animals. These results suggest that preemptive HO-1 gene delivery may be useful as a therapeutic strategy to reduce post-MI LV remodeling and heart failure.     

Heart failure progression is accelerated following myocardial infarction in type 2 diabetic rats

Clinical studies have shown a greater incidence of myocardial infarction in diabetic patients, and following an infarction, diabetes is associated with an increased risk for the development of left ventricular (LV) dysfunction and heart failure. The goal of this study was to determine if the progression of heart failure following myocardial infarction in type 2 diabetic (T2D) rats is accelerated compared with nondiabetic rats. Male nondiabetic Wistar-Kyoto (WKY) and T2D Goto-Kakizaki (GK) rats underwent coronary artery ligation or sham surgery to induce heart failure. Postligation (8 and 20 wk), two-dimensional echocardiography and LV pressure measurements were made. Heart failure progression, as assessed by enhanced LV remodeling and contractile dysfunction, was accelerated 8 wk postligation in the T2D animals. LV remodeling was evident from increased end-diastolic and end-systolic diameters and areas in the GK compared with the WKY infarcted group. Furthermore, enhanced LV contractile dysfunction was evident from a greater deterioration in fractional shortening and enhanced myocardial performance index (an index of global LV dysfunction) in the GK infarcted group. This accelerated progression was accompanied by greater increases in atrial natriuretic factor and skeletal alpha-actin (gene markers of heart failure and hypertrophy) mRNA levels in GK infarcted hearts. Despite similar decreases in metabolic gene expression (i.e., peroxisome proliferator-activated receptor-alpha-regulated genes associated with fatty acid oxidation) between infarcted WKY and GK rat hearts, myocardial triglyceride levels were elevated in the GK hearts only. These results, demonstrating enhanced remodeling and LV dysfunction 8 wk postligation provide evidence of an accelerated progression of heart failure in T2D rats.     

Interaction between left ventricular wall motion and intraventricular flow propagation in acute and chronic ischemia

Myocardial ischemia has been associated with left ventricular (LV) postsystolic shortening. The combination of tissue Doppler imaging and high frame-rate acquisition of two-dimensional color flow makes it possible to study the interaction between LV wall motion and intraventricular flow propagation. The aim of this study was to examine in a clinical model the impact that acute myocardial ischemia and prior myocardial infarct might have on LV flow patterns and to explain the underlying mechanisms from the tissue Doppler data. LV flow propagation and tissue velocities during early diastole were studied in 18 healthy individuals, 17 patients with prior anterior myocardial infarct, and 16 patients before and during percutaneous coronary intervention (PCI) of the left anterior descending artery. Normal individuals had intraventricular flow propagation toward the apex during isovolumic relaxation. During this early diastolic time phase, myocardial velocities measured at mid- and apical septal segment were directed away from the apex. Before PCI, patients without myocardial infarction had similar findings as in normal individuals. In contrast, each patient with either prior myocardial infarction or PCI-induced acute ischemia had flow propagation opposite to normal individuals, and tissue velocities reversed toward the apex during early diastole. Reversal of early diastolic LV flow propagation in acute and chronic anterior myocardial ischemia reflects postsystolic shortening in the dyskinetic apical and septal myocardial segments.     

Ghrelin对心肌梗死后心肌重塑及心脏功能的影响及其机制研究

目的:观察ghrelin对心肌梗死(MI)大鼠心肌重塑和心脏功能的影响,并探讨其可能的机制。方法:应用冠状动脉结扎术创建大鼠MI模型,并设立假手术组作为对照;造模成功后每天2次注射ghrelin(100μg/kg),持续4周,以此作为MI-ghrelin组,并以每天注射生理盐水的MI大鼠作为MI-生理盐水组。检测和比较各组大鼠左心室重塑和血流动力学的改变情况;非梗死心肌中白介素(IL)-1β、肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶(MMP)-2、MMP-9 mRNA和蛋白的表达;梗死边界心肌细胞的凋亡情况。结果:Ghrelin可使心肌梗死后的MI大鼠降低的缩短分数(FS)、左室内压最大变化率均显著下降(dP/dtmax)、疤痕厚度明显升高,增加左室舒张末压(LVEDP)、左室收缩末内径(LVESD)、左室舒张末期内径(LVEDD)、梗死边界心肌细胞的凋亡指数显著降低。此外,ghrelin可抑制心肌梗死后的MI大鼠非梗死心肌中白介素(IL)-1β、肿瘤坏死因子-α(TNF-α)、质金属蛋白酶(MMP)-2和MMP-9的mRNA和蛋白的表达。结论:Ghrelin可缓解MI后大鼠LV功能紊乱及心室重塑,这可能与其抑制炎症反应及基质金属蛋白酶的表达有关。     

Validation of the wall motion score and myocardial performance indexes as novel techniques to assess cardiac function in mice after myocardial infarction

The aim of this study was to determine the feasibility and accuracy of wall motion score index (WMSI) and myocardial performance index (MPI) for measuring regional and global left ventricular (LV) function with use of high-resolution echocardiography after myocardial infarction (MI) in mice. In 48 mice, myocardial infarction was induced by ligation in the middle of the left anterior descending coronary artery. Echocardiography was performed under anesthesia at baseline and 1 mo after MI. WMSI was analyzed by a 16-segment model on short-axis views, and wall motion was scored as 1 for normal, 2 for hypokinetic, 3 for akinetic, 4 for dyskinetic, and 5 for aneurysmal. WMSI was calculated as the sum of scores divided by the total number of segments. MPI was calculated on the basis of isovolumetric contraction time (IVCT), isovolumetric relaxation time (IVRT), and ejection time (ET): MPI = (IVCT + IVRT)/ET. We measured LV ejection fraction (LVEF), end-systolic and end-diastolic volumes (ESV and EDV), fractional shortening (FS), and infarct size (IS). LVEF at 4 wk after MI was reduced at 32.8 +/- 9.0%. Linear correlation analyses showed that WMSI (1.6 +/- 0.3) correlated with LVEF (r = -0.84, P < 0.0005), FS (r = -0.43, P = 0.003), and IS (34.3 +/- 15.3%, r = 0.86, P < 0.0005). MPI (0.67 +/- 0.09) correlated with LVEF (r = -0.67, P < 0.0005) and IS (r = 0.72, P < 0.0005). MPI also correlated with mitral inflow velocity (r = -0.68, P < 0.0005) and deceleration time (r = -0.42, P = 0.003). Stepwise regression analysis revealed that WMSI was independently associated with IS. IS, FS, mitral inflow velocity, and deceleration time were independent determinants of MPI. In conclusion, echocardiographic assessments of WMSI and MPI in mice are feasible and correlate strongly with two-dimensional measurement of LV function and IS. These novel parameters provide additional noninvasive assessment of regional and global LV function in mice after MI.     

心肌带收缩率与急性心肌梗死患者左心室收缩功能关系

目的:急性前壁心肌梗死明显影响室间隔收缩率和左心室射血分数(left ventricular ejection fraction LVEF)。本文旨在探讨心肌带降段及升段收缩率与急性前壁心肌梗死患者LVEF的相关性。方法:收集2015年4月-2017年2月在心内科住院的急性前壁心肌梗死患者36例,正常对照组患者39例。所有患者取左心室长轴M型超声心动图,测量室间隔收缩率、升段收缩率及降段收缩率。心肌梗死左心室射血分数采用双平面Simpson's法计算。结果:与正常对照组相比,心肌梗死组患者舒张末期心肌带升段厚度没有统计学差异(P=0.69),收缩末期升段厚度(P=0.014)更薄、升段收缩率(P0.01)明显降低;心肌梗死组舒张末期降段厚度(P0.01)更薄、收缩末期降段厚度(P0.01)更薄、降段收缩率(P0.01)明显降低;心肌梗死组左心室射血分数与降段收缩率(r~2=0.13,P=0.026)、室间隔增厚率(r~2=0.19,P0.01)呈正相关,与升段收缩率没有相关性(P0.05)。正常对照组左心室射血分数与室间隔增厚率、降段增厚率及升段增厚率无相关性。经过相关分析,筛选出与心肌梗死LVEF的相关因素,进一步经逐步回归分析,得多元线性回归方程为LVEF=48.206+18.914*LVDD(cm)-25.414*LVSD(cm)。结论:急性前壁心肌梗死室间隔降段收缩率明显受损,与左心室射血分数降低有关。多元线性回归方程可估算前壁心肌梗死LVEF。     

Assessment of segmental wall motion abnormalities using contrast two-dimensional echocardiography in awake mice

Murine models of cardiac disease are becoming an important tool for studying pathophysiological processes. Development of methods to accurately assess ventricular function are therefore important. The purpose of this study was to evaluate the feasibility of echocardiographic assessment of segmental wall motion abnormalities in a murine model of myocardial infarction. Two-dimensional contrast (C+) and noncontrast (C-) echocardiography were performed in 76 awake mice 2 days before and 2 days after left coronary ligation. The short-axis images obtained with two-dimensional echocardiography and corresponding postmortem cross-sectional histological samples stained with Evans blue dye were each divided into 16 segments, and all matched segments were examined for correlation between wall motion abnormalities and myocardial hypoperfusion. With the use of contrast enhancement, the number of visualized segments was significantly increased (base: C- 86%, C+ 98%; midpapillary: C- 57%, C+ 89%; apex: C- 30%, C+ 74%). Agreement between echocardiographically assessed regional wall motion abnormalities and pathologically determined hypoperfusion in basal, midpapillary, and apical levels were 90%, 93%, and 93%, respectively. Agreement between echocardiographically normal wall motion and pathologically normal findings in basal, midpapillary, and apical levels were 99%, 88%, and 71%, respectively. Thus echocardiographic assessment of segmental wall motion in awake mice was feasible and the accuracy was improved with the use of a contrast agent.     

A new model of congestive heart failure in rats

Current rodent models of ischemia/infarct or pressure-volume overload are not fully representative of human heart failure. We developed a new model of congestive heart failure (CHF) with both ischemic and stress injuries combined with fibrosis in the remote myocardium. Sprague-Dawley male rats were used. Ascending aortic banding (Ab) was performed to induce hypertrophy. Two months post-Ab, ischemia-reperfusion (I/R) injury was induced by ligating the left anterior descending (LAD) artery for 30 min. Permanent LAD ligation served as positive controls. A debanding (DeAb) procedure was performed after Ab or Ab + I/R to restore left ventricular (LV) loading properties. Cardiac function was assessed by echocardiography and in vivo hemodynamic analysis. Myocardial infarction (MI) size and myocardial fibrosis were assessed. LV hypertrophy was observed 4 mo post-Ab; however, systolic function was preserved. LV hypertrophy regressed within 1 mo after DeAb. I/R for 2 mo induced a small to moderate MI with mild impairment of LV function. Permanent LAD ligation for 2 mo induced large MI and significant cardiac dysfunction. Ab for 2 mo followed by I/R for 2 mo (Ab + I/R) resulted in moderate MI with significantly reduced ejection fraction (EF). DeAb post Ab + I/R to reduce afterload could not restore cardiac function. Perivascular fibrosis in remote myocardium after Ab + I/R + DeAb was associated with decreased cardiac function. We conclude that Ab plus I/R injury with aortic DeAb represents a novel model of CHF with increased fibrosis in remote myocardium. This model will allow the investigation of vascular and fibrotic mechanisms in CHF characterized by low EF, dilated LV, moderate infarction, near-normal aortic diameter, and reperfused coronary arteries.     

Left ventricular systolic performance during prolonged strenuous exercise in female triathletes

BACKGROUND: The effect of prolonged strenuous exercise (PSE) on left ventricular (LV) systolic function has not been well studied in younger female triathletes. This study examined LV systolic function prior to, during and immediately following PSE (i.e., 40 km bicycle time trial followed by a 10 km run) in 13 younger (29 PlusMinus; 6 years) female triathletes. METHODS: Two-dimensional echocardiographic images were obtained prior to, at 30-minute intervals during and immediately following PSE. Heart rate, systolic blood pressure, end-diastolic and end-systolic cavity areas were measured at each time point. Echocardiographic and hemodynamic measures were also combined to obtain LV end-systolic wall stress and myocardial contractility (i.e., systolic blood pressure - end-systolic cavity area relation). RESULTS: Subjects exercised at an intensity equivalent to 90 PlusMinus; 3% of maximal heart rate. Heart rate, systolic blood pressure, systolic blood pressure - end-systolic cavity area relation and fractional area change increased while end-diastolic and end-systolic cavity areas decreased during exertion. CONCLUSIONS: PSE is associated with enhanced LV systolic function secondary to an increase in myocardial contractility in younger female triathletes.     

Validation of echocardiographic and Doppler indexes of left ventricular relaxation in adult hypertensive and normotensive rats

This study was performed to validate echocardiographic and Doppler techniques for the assessment of left ventricular (LV) diastolic function in spontaneously hypertensive rats (SHR) and normotensive Wistar rats. In 11 Wistar rats and 20 SHR, we compared 51 sets of invasive and Doppler LV diastolic indexes. Noninvasive indexes of LV relaxation were related to the minimal rate of pressure decline (-dP/dt(min)), particularly isovolumic relaxation time (IVRT), the Tei index, the early velocity of the mitral annulus (E(m)) using Doppler tissue imaging, and early mitral flow propagation velocity using M-mode color (r = 0.28-0.56 and P < 0.05-0.0001). When the role of systolic load was considered, the correlation between Doppler indexes of LV diastolic function and relaxation rate [(-dP/dt(min))/LV systolic pressure] improved (r = 0.48-0.86 and P = 0.004-0.0001, respectively). Similarly, Doppler indexes of LV diastolic function and the time constant of isovolumic LV relaxation (tau) correlated well (r = 0.50-0.84 and P = 0.0002-0.0001, respectively). In addition, eight SHR and eight Wistar rats were compared; their LV end-diastolic diameters were similar, whereas the SHR LV mass was greater. Furthermore, IVRT and Tei index were significantly higher and E(m) was lower in SHR. Moreover, tau was higher in SHR, demonstrating impaired LV relaxation. In conclusion, LV relaxation can be assessed reliably using echocardiographic and Doppler techniques, and, using these indexes, impaired relaxation was demonstrated in SHR.     

Lung ultrasound: a new tool for the cardiologist

Background

We have previously reported strain dyssynchrony index assessed by two-dimensional speckle tracking strain, and a marker of both dyssynchrony and residual myocardial contractility, can predict response to cardiac resynchronization therapy (CRT). A newly developed three-dimensional (3-D) speckle tracking system can quantify endocardial area change ratio (area strain), which coupled with the factors of both longitudinal and circumferential strain, from all 16 standard left ventricular (LV) segments using complete 3-D pyramidal datasets. Our objective was to test the hypothesis that strain dyssynchrony index using area tracking (ASDI) can quantify dyssynchrony and predict response to CRT.

Methods

We studied 14 heart failure patients with ejection fraction of 27 ± 7% (all≤35%) and QRS duration of 172 ± 30 ms (all≥120 ms) who underwent CRT. Echocardiography was performed before and 6-month after CRT. ASDI was calculated as the average difference between peak and end-systolic area strain of LV endocardium obtained from 3-D speckle tracking imaging using 16 segments. Conventional dyssynchrony measures were assessed by interventricular mechanical delay, Yu Index, and two-dimensional radial dyssynchrony by speckle-tracking strain. Response was defined as a ≥15% decrease in LV end-systolic volume 6-month after CRT.

Results

ASDI ≥ 3.8% was the best predictor of response to CRT with a sensitivity of 78%, specificity of 100% and area under the curve (AUC) of 0.93 (p < 0.001). Two-dimensional radial dyssynchrony determined by speckle-tracking strain was also predictive of response to CRT with an AUC of 0.82 (p < 0.005). Interestingly, ASDI ≥ 3.8% was associated with the highest incidence of echocardiographic improvement after CRT with a response rate of 100% (7/7), and baseline ASDI correlated with reduction of LV end-systolic volume following CRT (r = 0.80, p < 0.001).

Conclusions

ASDI can predict responders and LV reverse remodeling following CRT. This novel index using the 3-D speckle tracking system, which shows circumferential and longitudinal LV dyssynchrony and residual endocardial contractility, may thus have clinical significance for CRT patients.     

Cardiac diastolic dysfunction in conscious dogs with heart failure induced by chronic coronary microembolization

Left ventricular (LV) diastolic dysfunction is a fundamental impairment in congestive heart failure (CHF). This study examined LV diastolic function in the canine model of CHF induced by chronic coronary embolization (CCE). Dogs were implanted with coronary catheters (both left anterior descending and circumflex arteries) for CCE and instrumented for measurement of LV pressure and dimension. Heart failure was elicited by daily intracoronary injections of microspheres (1.2 million, 90- to 120-microm diameter) for 24 +/- 4 days, resulting in significant depression of cardiac systolic function. After CCE, LV maximum negative change of pressure with time (dP/dt(min)) decreased by 25 +/- 2% (P < 0.05) and LV isovolumic relaxation constant and duration increased by 19 +/- 5% and 25 +/- 6%, respectively (both P < 0.05), indicating an impairment of LV active relaxation, which was cardiac preload independent. LV passive viscoelastic properties were evaluated from the LV end-diastolic pressure (EDP)-volume (EDV) relationship (EDP = be(alpha*EDV)) during brief inferior vena caval occlusion and acute volume loading, while the chamber stiffness coefficient (alpha) increased by 62 +/- 10% (P < 0.05) and the stiffness constant (k) increased by 66 +/- 13% after CCE. The regional myocardial diastolic stiffness in LV anterior and posterior walls was increased by 70 +/- 25% and 63 +/- 24% (both P < 0.05), respectively, after CCE, associated with marked fibrosis, increase in collagen I and III, and enhancement of plasminogen activator inhibitor-1 (PAI-1) protein expression. Thus along with depressed LV systolic function there is significant impairment of LV diastolic relaxation and increase in chamber stiffness, with development of myocardial fibrosis and activation of PAI-1, in the canine model of CHF induced by CCE.     

Long-Term Structural and Functional Myocardial Adaptations in Healthy Living Kidney Donors: A Pilot Study

Background and Aims

Compensatory renal hypertrophy following unilateral nephrectomy (UNX) occurs in the remaining kidney. However, the long-term cardiac adaptive process to UNX remains poorly defined in humans. Our goal was to characterize myocardial structure and function in living kidney donors (LKDs), approximately 12 years after UNX.

Methods and Results

Cardiac function and structure in 15 Italian LKDs, at least 5 years after UNX (median time from donation = 8.4 years) was investigated and compared to those of age and sex matched U.S. citizens healthy controls (n = 15). Standard and speckle tracking echocardiography (STE) was performed in both LKDs and controls. Plasma angiotensin II, aldosterone, atrial natriuretic peptide (ANP), N terminus pro B-type natriuretic peptide (NT-proBNP), cyclic guanylyl monophosphate (cGMP), and amino-terminal peptide of procollagen III (PIIINP) were also collected. Median follow-up was 11.9 years. In LKDs, LV geometry and function by STE were similar to controls, wall thickness and volumes were within normal limits also by CMR. In LKDs, CMR was negative for myocardial fibrosis, but apical rotation and LV torsion obtained by STE were impaired as compared to controls (21.4 ± 7.8 vs 32.7 ± 8.9 degrees, p = 0.04). Serum creatinine and PIIINP levels were increased [1.1 (0.9–1.3) mg/dL, and 5.8 (5.4–7.6)] μg/L, respectively), while urinary cGMP was reduced [270 (250–355) vs 581 (437–698) pmol/mL] in LKDs. No LKD developed cardiovascular or renal events during follow-up.

Conclusions

Long-term kidney donors have no apparent structural myocardial abnormalities as assessed by contrast enhanced CMR. However, myocardial deformation of the apical segments, as well as apical rotation, and LV torsion are reduced. The concomitant increase in circulating PIIINP level is suggestive of fibrosis. Further studies, focused on US and EU patients are warranted to evaluate whether these early functional modifications will progress to a more compromised cardiac function and structure at a later time.