Ryuhei Tanaka

Myocardial Na+,K(+)-ATPase in tachycardia induced cardiomyopathy.

Na+,K(+)-ATPase is a major determinant of myocyte homeostasis and excitation-contraction. Cardiac glycosides such as digitalis and ouabain increase the inotropic state of the heart through the inhibition of Na+,K(+)-ATPase. While cardiac glycosides are commonly used in the setting of congestive heart failure, optimal therapy would depend upon an intact Na+,K(+)-ATPase system. Changes in Na+,K(+)-ATPase activity and glycoside receptor density with the development of cardiomyopathy have not been well defined. Accordingly, left ventricular (LV) function and Na+,K(+)-ATPase activity and glycoside binding were examined in 7 pigs with dilated cardiomyopathy and in 7 controls. Dilated cardiomyopathy was produced by pacing induced supraventricular tachycardia (SVT) for 3 weeks at 240 bpm. Left ventricular function was examined by simultaneous echocardiography and catheterization. Left ventricular fractional shortening significantly decreased with SVT (34 +/- 2 vs. 10 +/- 2%, P less than 0.05) and LV diastolic dimension and pressure significantly increased (3.8 +/- 0.3 vs. 5.1 +/- 0.4 cm, and 8 +/- 2 vs. 27 +/- 2 mmHg, respectively, P less than 0.05) as compared to controls. Na+,K(+)-ATPase activity was assayed as potassium dependent p-nitrophenol-phosphatase activity. Glycoside receptor density (Bmax) and affinity (KD) was determined using [3H]-ouabain binding assays. Na+,K(+)-ATPase activity, Bmax, and KD all significantly fell from control values with SVT induced cardiomyopathy (0.64 +/- 0.06 vs. 0.45 +/- 0.12 micrograms pNP/mg/h, 5.5 +/- 0.4 vs. 1.9 +/- 0.4 pmol/mg, and 15 +/- 3 vs. 9 +/- 3 nM, respectively, P less than 0.05). The distribution of Na+,K(+)-ATPase in LV sections taken from control and SVT hearts were examined using immunohistochemical techniques. A patchy distribution of Na+,K(+)-ATPase along the sarcolemma in SVT sections was observed as opposed to a more uniform distribution in control myocytes. There was no observable change in the relative content and distribution of the Na+,K(+)-ATPase isoforms alpha 2 and alpha 3 in the SVT sections as compared to controls. In an additional set of experiments, changes in LV as well as isolated myocyte responsiveness to ouabain were examined. Left ventricular fractional shortening and peak dP/dt were measured following administration of 20-60 micrograms/Kg of ouabain in control (n = 3) and SVT (n = 3) pigs. In the control group, 40 micrograms/Kg caused a 25% in LV fractional shortening and a 60% increase in peak dP/dt from baseline. Cumulative doses of 60 micrograms/Kg in the control pigs resulted in over a 75% increase in peak dP/dt from baseline values.(ABSTRACT TRUNCATED AT 400 WORDS)

Left atrial function assessed by speckle tracking echocardiography as a predictor of new-onset non-valvular atrial fibrillation: results from a prospective study in 580 adults

AIMS The aim of this prospective study was to evaluate left atrial (LA) function for the prediction of increased risk of new-onset non-valvular atrial fibrillation (AF). Risk stratification for new-onset AF based on LA remodelling may have a major public health impact. Although left atrial volume (LAV) or LA dimension have been proposed as predictors of AF, other predictive parameters of LA function have not yet been fully examined. METHODS AND RESULTS LA emptying function (EF), strain rate (SR), and LAV were evaluated in the apical four-chamber view by speckle tracking echocardiography in 580 consecutive adults (age 64 ± 17, 303 men) without a history of atrial arrhythmias. During a follow-up period of 28 months, 32 subjects (age 73 ± 9, 18 men) developed electrocardiographically confirmed AF. Subjects with new-onset AF had lower LA active EF (16 ± 5 vs. 28 ± 8%, P< 0.001) and lower LA SR at atrial contraction (-0.9 ± 0.2 vs. -1.4 ± 0.5 S(-1), P< 0.001), but larger maximum LAV index (59 ± 12 vs. 46 ± 16 mL/m(2), P< 0.001) compared with non-AF subjects at baseline. In multivariate logistic regression analysis, LA active EF was the only independent predictor of new-onset AF. Using an LA active EF cut-off of ≤20%, the sensitivity and specificity for new-onset AF based on receiver operator characteristic curve analysis were 88 and 81%, respectively (area under the curve: 0.92). CONCLUSION Reduced LA active EF (booster pump function) assessed by speckle tracking echocardiography independently predicts the risk of new-onset AF, suggesting a stronger association between LA functional remodelling and AF than between LA size and AF.

Left atrial global and regional function in patients with paroxysmal atrial fibrillation has already been impaired before enlargement of left atrium: velocity vector imaging echocardiography study.

AIMS Left atrial volume (LAV) has been proposed as a predictor of atrial fibrillation (AF) and LA function has been investigated by velocity vector imaging (VVI) echocardiography. The aim of this study was to determine whether LA function was associated with the existence of AF. METHODS AND RESULTS We examined emptying function (EF) as a global function and strain rate (SR) as a regional function of LA function during three phases of the cardiac cycle (reservoir, conduit, and booster pump phase). The parameters were measured (apical four-chamber view) by VVI in 302 subjects [126 sinus rhythm, 91 paroxysmal AF (PAF), and 85 chronic AF]. Global and regional LA function were significantly lower in PAF patients during sinus rhythm (LA total EF: 35 ± 8%; SR at atrial contraction: -0.8 ± 0.3s(-1)) and much lower in chronic AF patients (LA total EF 22 ± 8%) than in subjects with sinus rhythm (LA total EF: 47 ± 7%; SR at atrial contraction: -1.4 ± 0.4s(-1)). In multivariate logistic regression analysis, LA active EF and SR at atrial contraction were independent features of PAF. CONCLUSION LA function, particularly LA active relaxation and contraction, was lower in PAF patients than in subjects with sinus rhythm, regardless of LA size and age. LA functional impairment was observed regardless of hypertension before LA enlargement in patients with PAF. Reduced LA function, as assessed by VVI, is an important feature of AF as well as LA structure.

Left ventricular volume determined echocardiographically by assuming a constant left ventricular epicardial long-axis/ short-axis dimension ratio throughout the cardiac cycle☆

OBJECTIVES The purpose of this study was to develop and test a simplified echocardiographic method to calculate left ventricular volume. BACKGROUND This method was based on the assumption that the ratio of the left ventricular epicardial long-axis dimension to the epicardial short-axis dimension was constant throughout the cardiac cycle. With use of this constant ratio, the method developed to calculate left ventricular volume at a given point in the cardiac cycle required the left ventricular endocardial long-axis dimension to be measured at only one point in the cardiac cycle. METHODS Studies were performed in 13 normal dogs, 8 normal puppies, 9 normal pigs, 12 dogs with aortic stenosis, 13 dogs with acute mitral regurgitation, 12 dogs with chronic mitral regurgitation, 7 dogs that had undergone mitral valve replacement and 6 pigs that had had chronic supraventricular tachycardia. Animals with aortic stenosis developed left ventricular pressure overload hypertrophy with a 60% increase in left ventricular mass; chronic mitral regurgitation caused left ventricular volume overload hypertrophy with a 46% increase in left ventricular volume; supraventricular tachycardia caused a dilated cardiomyopathy with a 55% decrease in left ventricular ejection fraction. RESULTS The left ventricular epicardial long-axis/short-axis dimension ratio remained constant throughout the cardiac cycle in each animal group. End-diastolic and end-systolic volumes calculated with the simplified echocardiographic method correlated closely with angiographically measured volumes; for end-diastolic volume, echocardiographic end-diastolic volume = 1.0 (angiographic end-diastolic volume) -1.8 ml, r = 0.96; for end-systolic volume, echocardiographic end-systolic volume = 0.98 (angiographic end-systolic volume) -0.7 ml, r = 0.95. CONCLUSIONS Thus the left ventricular epicardial long-axis/short-axis dimension ratio was constant throughout the cardiac cycle in a variety of animal species and age groups and in the presence of cardiac diseases that significantly altered left ventricular geometry and function. The simplified echocardiographic method examined provided an accurate determination of left ventricular volumes.

Effect of chronic supraventricular tachycardia on left ventricular function and structure in newborn pigs

OBJECTIVES The purpose of this study was to examine the effects of supraventricular pacing tachycardia on left ventricular function and myocardial structure in newborn, immature pigs and to determine whether immature pigs respond to supraventricular tachycardia differently from adults. BACKGROUND Previous studies have shown that supraventricular tachycardia causes dilated cardiomyopathy in adult animals; however, in humans, supraventricular tachycardia-induced congestive heart failure occurs most frequently in children and newborns. Because some clinical diseases may cause myocardial failure in adults but rarely do so in children, it was hypothesized that the effects of supraventricular tachycardia in newborns may be different from those in adults. METHODS In two groups of newborn swine (3 weeks of age), left ventricular volume, mass and function were assessed with simultaneous echocardiography and cardiac catheterization and myocardial structure was examined with light and electron microscopy. Six piglets underwent 3 weeks of left atrial pacing tachycardia (240 beats/min) and six littermates served as a control group. Both groups were followed up for 3 weeks. RESULTS At the end of the protocol, left ventricular dimensions increased in the piglets with supraventricular tachycardia compared with values in the control group, but there were no differences in left ventricular mass. Systolic function, assessed by fractional shortening, peak ejection rate and maximal rate of pressure development, was decreased in the group with supraventricular tachycardia. The fractional shortening-end-systolic stress relation in the piglets with supraventricular tachycardia decreased below normal values. Left ventricular diastolic function assessed by the relaxation time constant was prolonged, the peak filling rate was decreased and left ventricular stiffness was increased in the supraventricular tachycardia group. The morphologic data demonstrated that supraventricular tachycardia did not change total myocyte volume but did decrease total myofibrillar volume. CONCLUSIONS Supraventricular tachycardia caused dilated cardiomyopathy in immature pigs. These changes in left ventricular function were associated with a decrease in cellular contractile proteins. Thus, the effects of supraventricular tachycardia on left ventricular function and structure in immature animals were comparable to previous findings in mature animals.

Quantitative validation of left atrial structure and function by two-dimensional and three-dimensional speckle tracking echocardiography: a comparative study with three-dimensional computed tomography.

BACKGROUND The aim of this study was to validate the accuracy of three-dimensional (3D) speckle tracking echocardiography (STE) and two-dimensional (2D)-STE for the assessment of left atrial (LA) volume and function by comparison with 3D-computed tomography (CT) performed on the same day as STE. METHODS LA phasic volume and emptying function (EF) were measured in 28 patients with paroxysmal atrial fibrillation undergoing catheter ablation (62±11 years old) using both 3D-STE and 2D-STE during sinus rhythm. LA phasic volume and function measured by 3D-STE and 2D-STE were validated using 3D-CT as a gold standard. RESULTS The intraobserver correlation coefficient and variability in maximum LA volume assessed by 3D-STE were 0.99 and 1.4±6.0%, respectively. The interobserver correlation coefficient and variability in maximum LA volume assessed by 3D-STE were 0.99 and 0.2±4.5%, respectively. There were strong correlations between LA phasic volume measured by 3D-CT and those measured by 3D-STE (r=0.98, p<0.001). There were correlations between LA phasic function measured by 3D-CT and those measured by 3D-STE (r=0.85-0.88, p<0.001). There was a better agreement between 3D-CT and 3D-STE in the assessment of LA phasic volumes and function than between 3D-CT and 2D-STE in apical 2- and 4-chamber view. CONCLUSIONS 3D-STE allows more accurate measurement of LA volume and function than 2D-STE and has high reproducibility.

The effects of complete versus incomplete mitral valve repair in experimental mitral regurgitation

Severe mitral regurgitation (regurgitant fraction 0.75 +/- 0.02) was created in eight dogs by our closed-chest chordal rupture technique. After 3 months of chronic mitral regurgitation all indices of contractile function were depressed. Mitral valve repair was then attempted. Postoperative regurgitant fraction was reduced compared with the preoperative value in all eight dogs. Concomitantly, forward cardiac output increased in all dogs and pulmonary capillary wedge pressure fell in all dogs. However, in some dogs, significant regurgitation persisted despite repair. Postoperative regurgitant fraction ranged from 0% to 60%. Postoperative residual regurgitant fraction was related significantly to postoperative cardiac output (r = 0.99), pulmonary capillary wedge pressure (r = 0.77), ejection fraction (r = 0.75), and two indices of contractile function--the mass-corrected end-systolic stress volume relationship (r = 0.87) and end-systolic stiffness (r = 0.93). In general, these parameters returned to their normal values before mitral regurgitation when postoperative regurgitant fraction was less than 30%. Myocytes isolated from the ventricles at the end of study also demonstrated normal contractile function when regurgitant fraction was less than 30%.

Left atrial appendage emptying fraction assessed by a feature-tracking echocardiographic method is a determinant of thrombus in patients with nonvalvular atrial fibrillation

BACKGROUND Left atrial appendage (LAA) thrombus increases the risk of thromboembolism in atrial fibrillation (AF), and LAA contractile function like emptying fraction (EF) should have physiological importance in thrombus formation. The aim of this study was to validate a velocity vector imaging (VVI) method for quantification of the LAA function and to elucidate echocardiographic parameters that are related to the presence of LAA thrombus in patients with nonvalvular AF. METHODS We measured left atrial (LA) dimension and LAEF by VVI using transthoracic echocardiography, and LAA emptying velocity, spontaneous echo contrast (SEC), and LAAEF by VVI using transesophageal echocardiography (TEE) in 142 consecutive patients with nonvalvular AF. The patients were divided into two groups according to the presence (n=38) or absence (n=104) of LAA thrombus. RESULTS There was a good correlation between the VVI method and manual-tracing method for LAAEF and LAEF of patients with AF (r=0.97, r=0.96, respectively, p<0.001). LAAEF in AF with thrombus was significantly reduced compared with AF without thrombus (16.9±3.1% and 29.0±9.7%, p<0.001). In multivariate logistic regression analysis, LAAEF, SEC, and prior stroke were independent determinants of LAA thrombus. Using 20% of LAAEF as a cutoff value, the sensitivity was 92% and specificity was 88% for LAA thrombus. CONCLUSION The VVI method was reliable in the measurement of LAAEF and LAEF compared with the manual-tracing method. LAAEF assessed by the VVI method using TEE was related to the presence of LAA thrombus.

Association among blood pressure control in elderly patients with hypertension, left atrial structure and function and new-onset atrial fibrillation: a prospective 2-year study in 234 patients

We assessed the hypothesis that blood pressure (BP)-lowering therapy has a beneficial effect on left atrial (LA) structure and function and may decrease the incidence of new-onset atrial fibrillation (AF) in elderly patients with hypertension (HTN). We divided 234 subjects ⩾65 years old into four groups based on mean office BP achieved: a normotensive group (n=71), a HTN group with good BP control (n=72), a HTN group with poor BP control (n=41) and a HTN group with moderate BP control (n=50). LA volume, emptying function (EF), strain and strain rate (SR) were measured by speckle tracking echocardiography. LA volume, EF, strain and SR in the HTN group with good BP control were better preserved than those parameters in the HTN group with poor BP control. The incidence of new-onset AF during 2 years was significantly higher in the HTN group with poor BP control (hazard ratio: 7.015; 95% confidence interval: 2.433–20.22; P<0.001). In multivariate Cox regression analysis that included the difference in echocardiographic parameters between baseline and follow-up, both age and being in the HTN group with poor BP control were independent predictors of new-onset AF. In multivariate Cox regression analysis that included only parameters at baseline, ratio of the peak early transmitral flow velocity (E) to the peak early myocardial tissue velocity (E/e′) was an independent predictor of new-onset AF. The incidence of new-onset AF depended on the long-term level of BP control rather than short-term changes in LA structure and function. Poor BP control increased the risk of new-onset AF in elderly patients with HTN.

ESTIMATION OF LEFT VENTRICULAR CONTRACTILE FUNCTION IN HYPERTENSION BY MYOCARDIAL GLOBAL STRAIN RATE USING NOVEL REAL-TIME THREE-DIMENSIONAL SPECKLE TRACKING ECHOCARDIOGRAPHY WITH HIGH VOLUME RATE

Left ventricular (LV) systolic properties in hypertension (HTN) may be impaired by pressure overload, resulting in heart failure (HF) with reduced ejection fraction (EF). Using tissue Doppler and 2-dimensional speckle tracking echocardiography (2D-STE), LV myocardial strain rate (SR) was reported as