Soluble vascular endothelial growth factor receptor 2 and prognosis in patients with chronic heart failure.

AIMS: Endothelial cell vascular endothelial growth factor receptor 2 (VEGFR-2) plays a pivotal role in angiogenesis, which induces physiological cardiomyocyte hypertrophy via paracrine signalling between endothelial cells and cardiomyocytes. We investigated whether a decrease in circulating soluble VEGFR-2 (sVEGFR-2) levels is associated with poor prognosis in patients with chronic heart failure (HF). METHODS AND RESULTS: We performed a multicentre prospective cohort study of 1024 consecutive patients with HF, who were admitted to hospitals due to acute decompensated HF and were stabilized after initial management. Serum levels of sVEGFR-2 were measured at discharge. Patients were followed up over 2 years. The outcomes were cardiovascular death, all-cause death, major adverse cardiovascular events (MACE) defined as a composite of cardiovascular death and HF hospitalization, and HF hospitalization. The mean age of the patients was 75.5 (standard deviation, 12.6) years, and 57% were male. Patients with lower sVEGFR-2 levels were older and more likely to be female, and had greater proportions of atrial fibrillation and anaemia, and lower proportions of diabetes, dyslipidaemia, and HF with reduced ejection fraction (<40%). During the follow-up, 113 cardiovascular deaths, 211 all-cause deaths, 350 MACE, and 309 HF hospitalizations occurred. After adjustment for potential clinical confounders and established biomarkers [N-terminal B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin I, and high-sensitivity C-reactive protein], a low sVEGFR-2 level below the 25th percentile was significantly associated with cardiovascular death [hazard ratio (HR), 1.79; 95% confidence interval (CI), 1.16-2.74] and all-cause death (HR, 1.43; 95% CI, 1.04-1.94), but not with MACE (HR, 1.11; 95% CI, 0.86-1.43) or HF hospitalization (HR, 1.03; 95% CI, 0.78-1.35). The stratified analyses revealed that a low sVEGFR-2 level below the 25th percentile was significantly associated with cardiovascular death (HR, 1.76; 95% CI, 1.07-2.85) and all-cause death (HR, 1.49; 95% CI, 1.03-2.15) in the high-NT-proBNP group (above the median), but not in the low-NT-proBNP group. Notably, the patients with high-NT-proBNP and low-sVEGFR-2 (below the 25th percentile) had a 2.96-fold higher risk (95% CI, 1.56-5.85) for cardiovascular death and a 2.40-fold higher risk (95% CI, 1.52-3.83) for all-cause death compared with those with low-NT-proBNP and high-sVEGFR-2. CONCLUSIONS: A low sVEGFR-2 value was independently associated with cardiovascular death and all-cause death in patients with chronic HF. These associations were pronounced in those with high NT-proBNP levels.

Control of Mitochondrial Localization Using Thermoresponsive Sulfobetaine Polymer.

Fast intracellular migration and controlled localization of molecules represent significant challenges for future applications of drug discovery and related fields. In this study, thermoresponsive sulfobetaine polymers with pyridinium cations are evaluated as biocompatible and mitochondria-localizing agents. Among the polymers, poly(3-(4-(2-methacrylamido)ethyl pyridinio-1-yl)propane-1-sulfonate), P(E-PySMAAm)14k (Mn  = 14 000 g mol-1 ) exhibit thermoresponsiveness with an upper critical solution temperature like behavior in cell culture medium containing serum with minimal cytotoxicity. Upon the addition of P(E-PySMAAm)14k to HeLa cells at temperatures above the clearing point at 37 °C, effective localization is observed in mitochondria. However, increased intensity but nonspecific localization is observed below the clearing point at 4 °C. Doxorubicin is conjugated to the P(E-PySMAAm) and achieves effective mitochondrial delivery while maintaining drug efficacy. Such sulfobetaine polymers represent promising tools for intracellular delivery of molecules.

Fast and effective mitochondrial delivery of ω-Rhodamine-B-polysulfobetaine-PEG copolymers.

Mitochondrial targeting and entry, two crucial steps in fighting severe diseases resulting from mitochondria dysfunction, pose important challenges in current nanomedicine. Cell-penetrating peptides or targeting groups, such as Rhodamine-B (Rho), are known to localize in mitochondria, but little is known on how to enhance their effectiveness through structural properties of polymeric carriers. To address this issue, we prepared 8 copolymers of 3-dimethyl(methacryloyloxyethyl)ammonium propane sulfonate and poly(ethyleneglycol) methacrylate, p(DMAPS-ran-PEGMA) (molecular weight, 18.0 < M n < 74.0 kg/mol) with two different endgroups. We labeled them with Rho groups attached along the chain or on one of the two endgroups (α or ω). From studies by flow cytometry and confocal fluorescence microscopy of the copolymers internalization in HeLa cells in the absence and presence of pharmacological inhibitors, we established that the polymers cross the cell membrane foremost by translocation and also by endocytosis, primarily clathrin-dependent endocytosis. The most effective mitochondrial entry was achieved by copolymers of M n < 30.0 kg/mol, lightly grafted with PEG chains (< 5 mol %) labeled with Rho in the ω-position. Our findings may be generalized to the uptake and mitochondrial targeting of prodrugs and imaging agents with a similar polymeric scaffold.

Heart Failure With Preserved Ejection Fraction　- Time for a Paradigm Shift Beyond Diastolic Function.

At present, heart failure with preserved ejection fraction (HFpEF) is a commonly accepted condition in HF patients. In contrast to HF with reduced EF (HFrEF), HFpEF is strongly associated with aging, and vascular, metabolic, neurohormonal, and systemic inflammatory comorbidities. Two major hypotheses explain the pathophysiology of HFpEF (stages C,D in the American College of Cardiology Foundation/American Heart Association HF staging system): (1) impaired active relaxation and increased passive stiffness of the left ventricular (LV) myocardium during diastole (left atrial [LA]-LV coupling); and (2) LV and arterial stiffening during systole (LV-arterial coupling). Cardiac structural and functional abnormalities can be evaluated using non-invasive measures, such as 2-D, flow velocity Doppler, and tissue Doppler echocardiography, to estimate LV filling pressure and afterload mismatch. The clinical application of 2-D speckle-tracking echocardiography (2D-STE) is feasible for earlier diagnosis of functional abnormalities of the LA, LV, and elastic arteries in asymptomatic patients with cardiovascular risk factors (stages A,B). The goal of this review is to highlight the role of 2D-STE to detect impairment of LA-LV-arterial coupling beyond diastolic function earlier, because it may provide important information on the pathophysiology and prevention of HFpEF.

Challenges for 'diastology': contributions from Japanese researchers.

Diastology is a study to treat diastole of the heart. Transmitral flow and pulmonary venous flow velocities recorded by pulsed Doppler echocardiography provide more important information about left ventricular (LV) diastolic dysfunction [left atrial (LA)-LV coupling] than cardiac catheterization in clinical practice; however, these waveforms are influenced by loading conditions, particularly preload. The early diastolic mitral annular and LV wall motion indices measured by tissue Doppler echocardiography can evaluate LV relaxation abnormality and filling pressure by being relatively preload independent. In addition, the role of concomitant systolic longitudinal dysfunction is well characterized in asymptomatic patients and in patients with heart failure and preserved ejection fraction. Two-dimensional speckle tracking echocardiography is an angle-independent method, and has the potential to evaluate the contraction and relaxation abnormalities in the longitudinal, circumferential, and radial directions of the LV myocardium as well as LV torsion/untwisting and, moreover, deformation of the LA myocardium and large arterial wall. As a result, this new technique can facilitate the early detection of impaired LA-LV-arterial coupling in patients before occurrence of overt heart failure symptoms.

Association of left atrial reservoir function with left atrial structural remodeling related to left ventricular dysfunction in asymptomatic patients with hypertension: evaluation by two-dimensional speckle-tracking echocardiography.

Left atrial (LA) structural and functional abnormalities are vital steps on the pathway toward heart failure with preserved ejection fraction in asymptomatic patients. The purpose of this study was to assess the relationship of LA function, particularly reservoir function, with LA structural remodeling related to the left ventricular (LV) dysfunction in asymptomatic patients with hypertension (HT) using conventional, tissue Doppler, and 2-D speckle-tracking echocardiography. Fifty age-matched healthy individuals and 140 patients with HT, including 75 with LA volume index (LAVI)<29 ml/m2 (normal LA group) and 65 with LAVI≥29 ml/m2 (large LA group), were enrolled. We defined peak early diastolic transmitral flow velocity/peak early diastolic mitral annular motion velocity (E/e')/peak systolic LA strain (S-LAs) as LA diastolic stiffness. The LV mass index, relative LV wall thickness, peak atrial systolic transmitral flow velocity, LA total, active, and passive emptying volume indexes, and E/e'/S-LAs were greatest, and S-LAs, peak early diastolic LA strain, peak systolic LV longitudinal strain and circumferential strain rate, and peak early diastolic LV radial strain rate were lower in the large LA group compared with control and/or normal LA group. Multivariate linear regression analysis revealed that aging, LA remodeling, and LV systolic and diastolic dysfunction are defined as strong predictors related to increased LA diastolic stiffness in the large LA group. HT alters LA dynamics significantly, with resultant increased LA volume and diastolic stiffness related to LV diastolic and systolic dysfunction, even in asymptomatic patients. Earlier treatment with renin–angiotensin system inhibitors may improve abnormal LA-LV interaction in this patient population.

Influence of comorbid cardiovascular risk factors on left atrial-left ventricular interaction in asymptomatic patients: clinical application of two-dimensional speckle-tracking echocardiography.

Previous studies have examined the negative impacts of individual cardiovascular risk (CVR) factors on left atrial (LA)-left ventricular (LV) interaction, whereas the combined effects of these risk factors are insufficiently elucidated. We studied 176 asymptomatic patients with CVR factors and age-matched 50 healthy individuals by conventional and 2-dimensional speckle-tracking echocardiography. The patients were classified into 2 groups according to the number of CVR factors: one risk factor (single) group (n = 79) and 2 or more risk factors (comorbid) group (n = 97). The peak early diastolic transmitral flow velocity (E)/peak early diastolic mitral annular motion velocity (e')/peak systolic LA strain (S-LAs) was used as a surrogate for LA stiffness during ventricular systole. The E/e'/S-LAs was greatest in the comorbid group. The peak systolic LV circumferential and radial strains, peak early diastolic LV radial strain rate, and peak early diastolic LA strain and strain rate were lower in the comorbid group than in the single group. Multivariate regression analysis identified age, body mass index, systolic blood pressure, end-systolic LV diameter, peak systolic mitral annular motion velocity (s'), and peak systolic LV radial strain in the comorbid group, and peak atrial systolic transmitral fl ow velocity and s' in the single group, as independent predictors of E/e'/S-LAs. Subtle LA and LV dysfunction with individual CVR factors were more aggravated with the comorbid conditions in asymptomatic patients.

Contribution of obesity to left atrial and left ventricular dysfunction in asymptomatic patients with hypertension: A two-dimensional speckle-tracking echocardiographic study.

Hypertension and obesity each are well known to result in heart failure with preserved ejection fraction. Therefore, it is clinically important to clarify the mechanisms of further deterioration of left atrial (LA)-left ventricular (LV) interaction in asymptomatic patients with obesity in the presence of hypertension. Data on conventional and two-dimensional speckle-tracking echocardiography (2DSTE) were obtained from 134 asymptomatic hypertensive patients. The study sample was divided into two groups: non-obese (n = 80; body mass index [BMI] <25 kg/m(2)] and obese (n = 54; BMI ≥25 kg/m(2)). The end-diastolic LV diameter, ratio of early transmitral flow to mitral annular motion velocity (E/e'), peak systolic LV circumferential strain rate, and E/e'/peak systolic LA strain (S-LAs) were greater in the obese group. Among the significantly correlated variables with BMI and E/e'/S-LAs in univariate analyses, multivariate analyses revealed that BMI is independently associated with end-diastolic LV diameter and peak systolic LV radial strain in all hypertensive patients, and that age, systolic blood pressure, relative LV wall thickness, peak systolic mitral annular motion velocity (s'), peak systolic LV radial strain, and peak early diastolic LV longitudinal strain rate are identified as independent predictors related to E/e'/S-LAs in the obese patients, whereas only s' contributes to the E/e'/S-LAs in the non-obese patients. Impaired LA-LV interaction was accelerated with obesity in the presence of hypertension. Assessment of the LA and LV function using 2DSTE provided additional information to the negative effects of cardiovascular risk factors on the LA and LV function in patients without clinical symptoms.

The impact of hypertension as a road to heart failure with preserved ejection fraction: diagnostic value of two-dimensional speckle tracking echocardiography for the early impairment of left atrial-left ventricular-arterial coupling.

Heart failure with preserved ejection fraction (HFPEF) is a syndrome that frequently occurs in older people and patients with cardiovascular risk factors, particularly hypertension. This syndrome is not a specific disease process, whereas is associated with high morbidity and mortality in patients with heart failure with reduced ejection fraction (HFREF) as well. Therefore, a "one size fits all" diagnosis strategy is unlikely to operate for patients with HFPEF. Assessment of left atrial (LA)-left ventricular (LV)-arterial coupling seems to have a clinical impact on hypertensive patients, because HF signs and symptoms have been found to be significantly related to inappropriate LA-LV interaction during diastole and LV-arterial interaction during systole. Two-dimensional speckle tracking echocardiography (2DSTE) is a new tool that may have a role in earlier detecting the impaired LA, LV, and arterial function in asymptomatic patients. This review explored the impact of LA-LV-arterial coupling in understanding the pathophysiology of hypertension as a road to HFPEF, and the possibilities of clinical application by using 2DSTE.

Negative impact of cardiovascular risk factors on left atrial and left ventricular function related to aortic stiffness--new application of 2-dimensional speckle-tracking echocardiography.

BACKGROUND: The aim of the present study was to detect earlier the negative effect of cardiovascular risk (CVR) factors on left atrial (LA) and left ventricular (LV) function related to abdominal aortic (AAO) stiffness using 2-dimensional speckle-tracking echocardiography (2DSTE) in asymptomatic patients. METHODS AND RESULTS: One hundred and twelve patients with CVR factors and 56 healthy individuals were studied. 2DSTE data were acquired for determination of LA and LV myocardial and AAO wall deformations. LA volume index, LV mass index, ratio of early diastolic transmitral flow to mitral annular velocity (E/e')/peak systolic LA strain (S-LAs), and AAO stiffness were greater, and peak early diastolic LV longitudinal strain rate (SR-LVe) was lower in the patient group. Among the significantly correlated variables with AAO stiffness on univariate analysis, multivariate linear regression analysis identified SR-LVe and (E/e')/S-LAs in the patient group, and only age in the healthy group, as independent predictor of AAO stiffness. CONCLUSIONS: Structural and functional changes in the LA and LV and AAO stiffening were accelerated with CVR factors, and higher AAO stiffness was associated with deteriorated LA compliance and impaired LV relaxation in asymptomatic patients with CVR factors. 2DSTE has a potential for earlier detection of abnormal LA and LV function related to increased AAO stiffness.

Early predictors of alterations in left atrial structure and function related to left ventricular dysfunction in asymptomatic patients with hypertension.

Our aim was to investigate the relationships between left atrial (LA) structural and functional changes and left ventricular (LV) dysfunction related to LV pressure overload in asymptomatic patients with hypertension. One hundred and twenty-six asymptomatic patients with hypertension and LV ejection fraction (EF) ≥ 60% were studied. Conventional, pulsed and tissue Doppler, and two-dimensional speckle-tracking echocardiography (2DSTE) were performed to seek the independent determinants for alterations in LA structure and function. LA volume index (LAVI) correlated with age, body mass index (BMI), end-diastolic ventricular septal thickness (VSth), end-diastolic LV posterior wall thickness, relative LV wall thickness (RWT), LV mass index, peak A velocity of transmitral flow, E/e', and peak systolic and early diastolic LA strains and strain rates. Peak LA strain during ventricular systole (S-LAs) correlated with age, BMI, heart rate (HR), end-systolic LV diameter, LAVI, VSth, RWT, LVEF, e', E/e', peak systolic LV radial strain, and peak early diastolic LV longitudinal strain rate. Multivariate regression analyses indicated that LV mass index, peak A velocity, E/e', and S-LAs are defined as strong predictors related to LAVI, and that BMI, HR, LAVI, and peak systolic LV radial strain are defined as strong predictors related to S-LAs. In conclusion, 2DSTE demonstrated that alterations in LA structure and function are mainly associated with LV diastolic and systolic dysfunction, respectively, in preclinical patients with hypertension.

Effect of an increase in left ventricular pressure overload on left atrial-left ventricular coupling in patients with hypertension: a two-dimensional speckle tracking echocardiographic study.

BACKGROUND: Two-dimensional speckle tracking echocardiography (2DSTE) has recently been applied to evaluate left atrial (LA) function in addition to left ventricular (LV) function. However, whether 2DSTE can provide insight into LA-LV interaction related to an increase in LV pressure overload remains unknown. METHODS: One hundred five asymptomatic patients with hypertension were studied by conventional, pulsed and tissue Doppler, and 2DSTE. Hypertensive patients were classified into 2 groups according to the ratio of early diastolic to atrial systolic velocity (E/A) of transmitral flow: E/A ≥ 1 (n = 37) and E/A < 1 (n = 68). We used (E/peak early diastolic mitral annular motion velocity [e'])/peak systolic LA strain (S-LAs) and E/e', as parameters of LA stiffness during ventricular systole and LV diastolic stiffness, respectively. RESULTS: The peak early diastolic LV longitudinal strain rate, and peak early diastolic LA strain and strain rate were lower in the E/A < 1 group than in the E/A ≥ 1 group. The E/e'/S-LAs and E/e' were greater in the E/A < 1 group. In the E/A < 1 group, systolic blood pressure (SBP) correlated with LV wall thickness parameters, A, e', E/e', peak early diastolic LV longitudinal strain rate, and E/e'/S-LAs. Multivariate regression analysis indicated that A, E/e', and E/e'/S-LAs were defined as strong predictors related to SBP. CONCLUSION: In patients with hypertension, an elevation in SBP leads to increased LA stiffness during ventricular systole and LV diastolic stiffness, in association with continued and further advanced LV diastolic dysfunction. 2DSTE is considered a sensitive tool for detecting abnormal LA-LV coupling related to an increased LV pressure overload.

Vascular aging of common carotid artery and abdominal aorta in clinically normal individuals and preclinical patients with cardiovascular risk factors: diagnostic value of two-dimensional speckle-tracking echocardiography.

Increased arterial stiffness is becoming an increasing health care problem as the population ages. Our aim was to detect the vascular aging of common carotid artery (CCA) and abdominal aorta (AAO) more easily and earlier using two-dimensional speckle-tracking echocardiography, and to evaluate the regional differences in mechanical properties related to changes in aging between the two arteries in preclinical patients. Twenty-nine clinically normal individuals and 68 preclinical patients with cardiovascular risk factors were examined. The peak circumferential strains were measured from the short-axis views of the CCA and AAO, and each stiffness ß was determined. The CCA and AAO diameters increased with advanced age, and the latter diameter was widely distributed in patients of 50 years or older. The mean strain and stiffness index of the AAO were greater and lower, respectively, than those of the CCA at all ages. The CCA and AAO strains decreased with age, expressing dramatic declines before the fifth decade of life. The CCA and AAO stiffness indices increased with age, expressing rapid ascents after the fifth decade of life, particularly in the AAO. The best markers of subclinical arterial aging were strain in younger persons and stiffness in older individuals. Two-dimensional speckle-tracking echocardiography is a new tool that can be used to directly and easily evaluate arterial function.

Early detection of abnormal left atrial-left ventricular-arterial coupling in preclinical patients with cardiovascular risk factors: evaluation by two-dimensional speckle-tracking echocardiography.

AIMS: Data are lacking on the left atrial (LA)-left ventricular (LV)-arterial coupling for evaluating the functional abnormalities in the left heart disease, whereas LA-LV or LV-arterial coupling has been recognized. This study was designed to earlier detect the abnormal LA-LV-arterial coupling using two-dimensional speckle-tracking echocardiography (2DSTE) in patients with cardiovascular risk factors and no overt cardiovascular disease. METHODS AND RESULTS: We studied 30 age-matched healthy individuals and 64 preclinical patients with cardiovascular risk factors, who measured carotid arterial intima-media thickness and stiffness ß by M-mode ultrasonography, and strain and strain rate of the LA and LV walls by 2DSTE. The stiffness ß and LA volume index (LAVI) were greater in the patient group than in the control group. However, the peak systolic LV longitudinal strain, peak systolic and early diastolic LV longitudinal strain rates, peak systolic and early diastolic LA strains and strain rates, and peak atrial systolic LA strain rate were lower in the patient group. There were correlations between the stiffness ß and the age, pulse pressure, LAVI, peak early diastolic LV longitudinal strain rate, and all LA strains and strain rate variables. Multivariate regression analysis indicated that peak early diastolic LV longitudinal strain rate and peak LA strain rate during ventricular systole are defined as strong predictors related to stiffness ß. CONCLUSION: Impaired LA and LV relaxation in the longitudinal direction are early signs of abnormal LA-LV coupling related to arterial stiffness in preclinical patients with cardiovascular risk factors. 2DSTE enables the quantitative assessment of the LA and LV function, and can be considered a sensitive tool for detecting the abnormal LA-LV-arterial coupling.

Aortic stiffness is strikingly increased with age ≥ 50 years in clinically normal individuals and preclinical patients with cardiovascular risk factors: assessment by the new technique of 2D strain echocardiography.

BACKGROUND: Various measures of aortic stiffness have been proposed as cardiovascular risk markers, but interest has now shifted to more direct and easier evaluation of aortic function. The present study was conducted to determine the feasibility of measuring aortic stiffness (ß) with two-dimensional (2D) strain echocardiography and the impact of age and gender on preclinical atherosclerosis. METHODS AND RESULTS: The peak circumferential strain of the abdominal aorta was measured using 2D strain echocardiography, and ß was determined in 54 clinically normal individuals and 104 patients with cardiovascular risk factors and no evidence of cardiovascular disease. The ß correlated significantly with age in all 158 patients. However, the relationship was nonlinear, and ß was markedly greater in patients ≥ 50 years. In 54 clinically normal individuals, the relationship was comparatively linear. The systolic blood pressure and pulse pressure were significantly greater in patients ≥ 50 years. There were no significant differences in ß and blood pressure parameters between genders. CONCLUSIONS: The ß increased dramatically with advanced age (≥ 50 years), regardless of gender, in clinically healthy and community-based patients with cardiovascular risk factors. The aortic circumferential strain was measured with 2D strain echocardiography which is a new tool that can be used to directly and easily evaluate aortic stiffness.

Clinical significance of the reversed mitral annular motion velocity wave at the beginning of the mitral valve closure.

BACKGROUND: Pulsed tissue Doppler imaging is increasingly used to record mitral annular motion (MAM) velocity pattern. A reversed MAM velocity wave (Cm) is commonly seen at the beginning of the mitral valve closure in timing, whereas the underlying mechanism and clinical significance have not been studied. METHODS: Conventional, pulsed Doppler, pulsed tissue Doppler, and two-dimensional strain echocardiography were performed in 100 consecutive patients with cardiovascular risk factors. RESULTS: There were no correlations between the peak Cm and the ratio of peak early diastolic transmitral flow velocity to peak early diastolic MAM velocity (E/Em) and Tei index. The peak Cm correlated with left ventricular (LV) ejection fraction, left atrial volume index (LAVI) and left atrial ejection fraction, isovolumic relaxation time, peak LV systolic strains and strain rates during atrial systole in the longitudinal and circumferential directions, and peak LV systolic strain rates in the longitudinal, circumferential, and radial directions. Multivariate linear regression analysis revealed that LAVI is a independent predictor related to peak Cm. CONCLUSION: The Cm is regulated by mitral annular motion velocity toward the LA due to closing of the mitral valve, and may be used as a predictive tool for determining the "disease history" of chronic LV diastolic dysfunction in patients with no marked elevation in the LV filling pressure.

Left ventricular untwisting during left atrial contraction: a marker for chronic left ventricular diastolic dysfunction?

BACKGROUND: Left ventricular (LV) untwisting is commonly seen during left atrial (LA) contraction. The purpose of this study was to test the hypothesis that this characteristic motion is associated with chronic LV diastolic dysfunction. METHODS AND RESULTS: Ninety-two patients with cardiovascular risk factors and 36 age-matched normal individuals were included in the present study, and were examined by echocardiography, including conventional, tissue Doppler, and two-dimensional speckle tracking methods, to clarify the predictors related to late diastolic untwisting rate (LDUTR). There was no significant difference in LV ejection fraction between patient and control groups. The ratio of peak early diastolic transmitral flow velocity to peak early diastolic mitral annular motion velocity (E/e') and LA volume index in the patient group were significantly greater compared to the ratio of peak early to late diastolic transmitral flow velocity (E/A) ≥1 group of the controls. The LDUTR in the E/A <1 group of the controls was significantly greater compared to the E/A ≥1 group of the controls and patient group. The LDUTR correlated with end-diastolic LV diameter, LA volume index, peak A velocity, E/e', relative LV wall thickness, and mean peak systolic LV radial strain. Multivariate regression analysis indicated that LA volume index is defined as a strong predictor related to LDUTR. CONCLUSIONS: Late diastolic LV untwisting reduces with a gradual increase in the LA size in patients with cardiovascular risk factors, and may reflect the disease history of chronic LV diastolic dysfunction.

Telmisartan improves morphologic and functional changes in both left ventricular myocardium and carotid arterial wall in patients with hypertension: assessment by tissue Doppler imaging and carotid ultrasonography.

OBJECTIVE: The aim of the present study was to clarify the beneficial effects of telmisartan on the morphologic and functional changes in left ventricular (LV) myocardium and carotid arterial wall in patients with hypertension (HT) using tissue Doppler imaging and carotid ultrasonography. METHODS: Telmisartan (20-40 mg daily) was administered to 35 previously untreated patients with HT. Conventional and pulsed tissue Doppler echocardiography were performed after medication had been continued for 1-2 months with normal values for blood pressure (BP) (phase I) and for 12 months (phase II). Subclinical atherosclerosis also was determined by measuring the intima-media thickness (IMT) and stiffness ß of the left and right common carotid arteries using B- and M-mode ultrasonography. RESULTS: In the phase II, the LV mass index and isovolumic relaxation time were lower, the peak systolic and early diastolic mitral annular motion velocities were greater compared to the phase I. The stiffness ß and mean IMT were lower in the phase II than in the phase I. On multivariate regression analyses, age, BP, and LV diastolic variables emerged as stronger predictors of carotid arterial IMT and stiffness ß. CONCLUSIONS: The 1-year use of telmisartan improved LV hypertrophy, regional LV myocardial contraction and relaxation, and carotid atherosclerosis in patients with HT. Our results support cardio- and arterioprotective benefits from continuous long-term telmisartan monotherapy, and combined analysis of tissue Doppler imaging and carotid ultrasonography may be a useful tool for understanding ventriculoarterial coupling in patients with HT.

Possible mechanisms of left ventricular torsion evaluated by cardioreparative effects of telmisartan in patients with hypertension.

AIMS: Left ventricular (LV) torsion may be an important component of normal LV systolic function. However, its mechanics remain unresolved. Two-dimensional (2-D) strain imaging is increasingly used to quantify LV torsion in the clinical setting. Telmisartan has cardioreparative effects, including attenuation of subendocardial myocardial fibrosis and improvement of LV remodelling. To clarify the mechanisms of LV torsion, in the present study, we evaluated changes in LV longitudinal deformation and torsion after medication with telmisartan using 2-D strain imaging in patients with hypertension (HT). METHODS AND RESULTS: Telmisartan (20-40 mg daily) was administered to 37 previously untreated patients with HT. Two-dimensional strain echocardiography was performed after medication had been continued for 1-2 months with normal values for blood pressure (BP) (phase I) and for 12 months (phase II). In the phase II, relative LV wall thickness, LV mass index, LV torsion, and torsional rate were reduced, whereas the mean peak systolic longitudinal strain and strain rate were increased, compared to the phase I. LV torsion correlated well with relative LV wall thickness, but not LV mass index. CONCLUSION: Our results obtained from cardioreparative effects of telmisartan suggested that LV torsion is associated with systolic longitudinal deformation related to subendocardial myocardial fibrosis, and/or LV concentric hypertrophy-related difference in torques between the subendocardial and subepicardial sides.

Concentric left ventricular hypertrophy brings deterioration of systolic longitudinal, circumferential, and radial myocardial deformation in hypertensive patients with preserved left ventricular pump function.

BACKGROUND: We hypothesized that deterioration of systolic left ventricular (LV) myocardial deformation exists as an early sign of "isolated" diastolic heart failure in patients with hypertension (HT) and LV hypertrophy (LVH). METHODS AND RESULTS: Two-dimensional strain echocardiography was performed in 98 patients with HT and 22 age-matched normal controls. The LV mass index and relative wall thickness were used to assign patients into 3 groups with normal geometry (N-LV, n=31), concentric hypertrophy (C-LVH, n=25), and eccentric hypertrophy (E-LVH, n=42). The LV ejection fraction was preserved (> or =50%) in the 3 HT groups. The mean peak systolic longitudinal, circumferential, and radial strains in the C-LVH group were lower compared to the control and other 2 HT groups. The mean peak systolic strain rates in the 3 directions in the C-LVH group and those in the longitudinal and radial directions in the E-LVH and N-LV groups were lower compared to the control group. In addition, the mean peak systolic circumferential strain rate was lower in the C-LVH group than in the other 2 HT groups. There were no differences in the LV torsion and torsional rate between the control and 3 HT groups. The mean peak systolic circumferential strain was an independent predictor related to LV ejection fraction in all patients. CONCLUSIONS: C-LVH caused deterioration of the systolic longitudinal, circumferential, and radial myocardial deformation in patients with HT. LV torsion and circumferential shortening were considered to be compensatory mechanisms for maintaining LV pump function.