Recurrent membranous nephropathy with a possible alteration in the etiology: a case report.

BACKGROUND: Phospholipase A2 receptor 1 (PLA2R1) and thrombospondin type-1 domain-containing 7A (THSD7A) are the two major pathogenic antigens for membranous nephropathy (MN). It has been reported that THSD7A-associated MN has a higher prevalence of comorbid malignancy than PLA2R1-associated MN. Here we present a case of MN whose etiology might change from idiopathic to malignancy-associated MN during the patient's clinical course. CASE PRESENTATION: A 68-year-old man with nephrotic syndrome was diagnosed with MN by renal biopsy. Immunohistochemistry showed that the kidney specimen was negative for THSD7A. The first course of corticosteroid therapy achieved partial remission; however, nephrotic syndrome recurred 1 year later. Two years later, his abdominal echography revealed a urinary bladder tumor, but he did not wish to undergo additional diagnostic examinations. Because his proteinuria increased consecutively, corticosteroid therapy was resumed, but it failed to achieve remission. Another kidney biopsy was performed and revealed MN with positive staining for THSD7A. PLA2R1 staining levels were negative for both first and second biopsies. Because his bladder tumor had gradually enlarged, he agreed to undergo bladder tumor resection. Pathological examination indicated that the tumor was THDS7A-positive bladder cancer. Subsequently, his proteinuria decreased and remained in remission. CONCLUSIONS: This case suggests that the etiology of MN might be altered during the therapeutic course. Intensive screening for malignancy may be preferable in patients with unexpected recurrence of proteinuria and/or change in therapy response.

HOXA10 expression profiling in prostate cancer.

BACKGROUND: HOX genes encode transcription factors that play key roles in modulating normal tissue morphogenesis, differentiation and homeostasis. Disruption of normal HOX gene expression occurs frequently in human cancers and is associated with both tumor promoting and suppressing activities. Among these is, HOXA10, a pleiotropic gene that is critical for normal prostate development. In this study we characterized HOXA10 expression in human and mouse PCa to gain insights into its clinical significance. METHODS: A meta-analysis of HOXA10 mRNA expression was carried out across several publicly available data sets. Expression of HOXA10 protein expression was assessed by immunohistochemistry (IHC) using human radical prostatectomy (RP) cases. We correlated HOXA10 expression to clinicopathological features and investigated its relationship to biochemical recurrence (BCR) after RP by the Kaplan-Meier method. HOXA10 mRNA and IHC protein expression was also examined in a mouse model of Pten-null PCa. RESULTS: A meta-analysis of HOXA10 gene expression indicated dysregulated expression of HOXA10 in human PCa. IHC profiling of HOXA10 revealed inverse correlations between HOXA10 expression and Gleason pattern, Gleason score, and pathological stage (P < 0.01). Patients with low expression profiles of HOXA10 were associated with a higher risk of BCR, (OR, 3.54; 95%CI, 1.21-16.14; P = 0.049) whereas patients with high HOXA10 expression experienced longer times to BCR (P = 0.045). However, HOXA10 was not an independent predictor of BCR (OR, 1.52; 95%CI, 0.42-5.54; P = 0.52). Evaluation of expression patterns of HOXA10 in mouse prostate tumors mimicked that of humans. CONCLUSIONS: Our findings show that HOXA10 expression is inversely associated with tumor differentiation and high HOXA10 expression is associated with improved BCR-free survival. This study provides human and mouse evidence to suggest tumor suppressive roles for HOXA10 in the context of prostate cancer.

Evaluation of in vivo responses of sorafenib therapy in a preclinical mouse model of PTEN-deficient of prostate cancer.

BACKGROUND: Despite recent advances in the treatment for advanced prostate cancer, outcomes remain poor. This lack of efficacy has prompted the development of alternative treatment strategies. In the present study we investigate the effects of the multikinase inhibitor sorafenib in a genetically engineered mouse model of prostate cancer and explore the rational combination with the mTOR inhibitor everolimus. METHODS: Conditional prostate specific PTEN-deficient knockout mice were utilized to determine the pharmacodynamic and chemopreventive effects of sorafenib. This mouse model was also used to examine the therapeutic efficacy of sorafenib alone or in combination with everolimus. Preclinical efficacy was assessed by comparing the reduction of tumor burden, proliferation, angiogenesis and the induction of apoptosis. Molecular responses were assessed by immunohistochemical, TUNEL and western blot assays. RESULTS: Pharmacodynamic analysis revealed that a single dose of sorafenib decreased activation of the PI3K/AKT/mTOR signaling axis at doses of 30-60 mg/kg, but activated JAK/STAT3 signaling. Levels of cleaved casapase-3 increased in a dose dependent manner. Chemoprevention studies showed that chronic sorafenib administration was capable of inhibiting tumor progression through the reduction of cancer cell proliferation, angiogenesis and the induction of apoptosis. In intervention models of established castration-naïve and castration-resistant prostate cancer, treatment with sorafenib provided modest but statistically insignificant reduction in tumor burden. However, sorafenib significantly inhibited cancer cell proliferation and MVD but had minimal effects on the induction of apoptosis. Interestingly, the administration of sorafenib increased the expression levels of the androgen receptor, p-GSK3ß and p-ERK1/2 in castration-resistant prostate cancers. In both intervention models, combination therapy demonstrated a clear tendency of enhanced antitumor effects over monotherapy. Notably, the treatment combination of sorafenib and everolimus overcame therapeutic escape from single agent therapy in castration-resistant prostate cancers. CONCLUSIONS: In summary, we provide insights into the molecular responses of sorafenib therapy in a clinically relevant model of prostate cancer and present preclinical evidence for the development of targeted treatment strategies based on the use of multikinase inhibitors in combination with mTOR inhibitors for the treatment of advanced prostate cancer.

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.

The Relationship between Leptin Levels and Continuous Positive Airway Pressure Treatment: A Cluster Analysis.

Objective Leptin is an appetite-suppressing hormone released by adipose tissue that plays an important role in severe obstructive sleep apnea syndrome (OSAS). However, it is unclear whether leptin levels are a useful biomarker for this syndrome. The present study aimed to assess the effect of continuous positive airway pressure (CPAP) treatment on the syndrome according to leptin levels, using a cluster classification based on clinical features of the syndrome. Materials and Methods We performed a hierarchical cluster analysis of data from 97 OSAS patients diagnosed via polysomnography. We also evaluated the effect after 6 months of CPAP administration. Results Clusters 1 (49 patients; 50.5%) and 2 (6 patients; 6.2%) presented normal leptin levels, and clusters 3 (11 patients; 11.3%) and 4 (31 patients; 32%) presented high leptin levels. Clusters 3 and 4 presented different leptin levels, but the same degree of obesity. After treatment, the levels of excessive daytime sleepiness improved in all clusters. In Cluster 3, leptin levels were significantly reduced after treatment. Conclusion Using the conventional diagnostic method of the apnea-hypopnea index, it was not clear whether leptin is a useful biomarker for the CPAP treatment. However, it may be helpful for particular clusters, including obese women, and where particular populations require CPAP treatment.

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.

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.

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.

[Granulocyte-colony stimulating factor-producing urothelial carcinoma of the renal pelvis : a case report].

A 43-year-old woman was referred to our hospital for fever, general fatigue and left flank abdominal pain during the last two weeks. A blood test showed severe inflammation, and computed tomography (CT) study of the abdomen with intravenous contrast revealed swelling and irregular enhancement in the upper left kidney. Initially, we diagnosed it as xanthogranulomatous pyelonephritis and treated it with antibiotics. A percutaneous renal biopsy was performed because the white blood cell count remained elevated after the treatment. Histopathologic examination revealed a carcinoma. Therefore, we performed left nephroureterectomy. The diagnosis was high grade urothelial carcinoma of the renal pelvis, and it stained positive by immunohistochemical staining using anti-granulocyte-colony stimulating factor (G-CSF). The serum G-CSF level was also elevated on the same day. The patient received chemotherapy but, died 9 months after surgery. A G-CSF-producing urothelial carcinoma of the renal pelvis is known to have a poor prognosis in the Japanese literature. It is important to closely monitor a G-CSF producing tumor, when a patient shows severe inflammation, but no infection.

Chronic eosinophilic pneumonia presenting with acute onset.

A 44-year-old woman was hospitalized with a 2-day history of cough, sputum, and fever. There was no history of atopic dermatitis or asthma. On admission, the chest X-ray revealed scattered infiltration in the left upper lung fields. Further examination revealed peripheral blood and bronchoalveolar lavage fluid eosinophilia. Transbronchial lung biopsy revealed eosinophilic pneumonia, with eosinophil infiltration of the alveoli, destroyed basal lumina, and connecting intraluminal fibrosis of the alveolar walls. Based on the findings, we made the diagnosis of chronic eosinophilic pneumonia. Treatment with prednisolone at 60 mg/day resulted in dramatic improvement of both the symptoms and the radiologic abnormalities.

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.

[Spontaneous renal artery dissection with renal infarction: a case report].

A 58-year-old woman visited our hospital with nausea and right flank pain. At first abdominal ultrasonography was performed, suggesting a right renal infarction. Computed tomography (CT) study of the abdomen with intravenous contrast was performed to determine the cause of the symptoms. The scan revealed poor enhancement in the lower half of the right kidney. She was diagnosed with a right renal infarction. She was initially treated with anticoagulant therapy, but 5 days later, she complained of nausea. This time, CT demonstrated exacerbation of a right renal infarction with renal artery dissection. Based on this finding, we performed a right nephrectomy. The result of pathology was segmental arterial mediolysis. She was discharged 12 days after the surgery and is doing well at 6 months after discharge. Spontaneous renal artery dissection is a rare disease. It constitutes approximately 0.05% of arteriographic dissections. In addition, spontaneous renal artery dissection shows nonspecific symptoms. Together, these two factors may cause a delay in diagnosis.

[A CASE OF UNRESECTABLE METASTATIC RENAL CARCINOMA SUCCESSFULLY TREATED BY COMBINED MODALITY THERAPY WITH NIVOLUMAB AND SURGERY].

The patient was a 65-year-old male who was referred with right renal mass (8 × 6.7 cm) and swelling of para-aortic lymph nodes in CT in April, 20XX. Additional examinations revealed inferior vena cava invasion, multiple lung metastases and left iliac bone metastasis and he was diagnosed with a renal cell carcinoma (cT4N1M1b). Pazopanib was administered as the first line treatment for an unresectable renal cancer. Nivolumab was then administrated as the 2nd line therapy due to the disease progression evaluated in (late) June, 20XX. However, immediately after the first administration of nivolumab, the patient have a difficulty in walking resulting from low-back pain, and MRI showed multiple lumbar vertebral metastases and L2 compression fracture. He was transferred to another hospital for combined modality therapy including right femoral head replacement and palliative radiotherapy in August, 20XX. Nivolumab was resumed since he had stable disease after his return to our hospital, and a total of 20 cycles of nivolumab treatment was performed. A follow-up CT showed 70% decrease in an initial primary tumor and tumor decrease or disappear in metastatic lung and bone tumors. The primary tumor was considered surgically resectable, and a radical nephrectomy was performed in August 20XX +1. Histopathological examination showed with a marked effect of neoadjuvant therapy and no evidence of viable tumor cells. We report a case of unresectable carcinoma that was successfully treated with nivolumab.

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.

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.

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.

A novel approach to assess aortic stiffness related to changes in aging using a two-dimensional strain imaging.

BACKGROUND: Recently, it has been demonstrated that aortic stiffness is associated with cardiovascular morbidity and mortality. The objective of the present study was to accurately evaluate the aortic stiffness relative to the changes in aging using two-dimensional (2D) strain imaging in 39 comparatively normal patients (15-85 years). METHODS: We obtained short-axis images of the abdominal aorta (Ao) and determined the peak circumferential strain (Ao-S) and strain rate (Ao-SR) and the time from Q-wave of electrocardiogram to peak Ao-S using the 2D strain imaging. The stiffness parameters beta(1) and beta(2) of the abdominal aorta were measured using M-mode ultrasonography and 2D strain imaging, respectively. RESULTS: The stiffness parameters beta(1) and beta(2) correlated significantly with age (r=0.51, P < 0.001 and r=0.69, P < 0.0001, respectively), particularly the latter parameter beta(2). The peak circumferential Ao-S and Ao-SR correlated strongly with age (r=-0.79, P < 0.0001 and r=-0.87, P < 0.0001, respectively). The stiffness parameter beta(1) was significantly greater in the old-aged group (>60 years) than in the young-aged group (<30 years). The peak circumferential Ao-S and Ao-SR were significantly lower in the middle-aged (30-60 years) and old-aged groups than in the young-aged group. CONCLUSION: The aortic circumferential strain and strain rate measured by 2D strain imaging allow simple and accurate determination of the aortic stiffness.

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.

Arterial stiffness is associated with left ventricular diastolic function in patients with cardiovascular risk factors: early detection with the use of cardio-ankle vascular index and ultrasonic strain imaging.

BACKGROUND: It is well known that left ventricular (LV) diastolic function declines in the elderly, especially in patients with cardiovascular risk factors. However, few data are available on the early detection of relationship between arterial stiffness and LV diastolic dysfunction. METHODS AND RESULTS: The common carotid artery intima-media thickness (IMT) and cardio-ankle vascular index (CAVI) were measured to determine the presence of subclinical atherosclerosis in 30 patients (13 men and 17 women; mean age 59 +/- 5.7 years) with 1 or more cardiovascular risk factors. LV systolic and diastolic function also were determined by measuring transmitral flow velocity, mitral annular motion velocity, and myocardial strain and strain rate profiles using pulsed Doppler, tissue velocity, and ultrasonic strain imaging. The CAVI correlated with the peak early diastolic velocity of transmitral flow velocity (r = -0.50, P < .01), the ratio of peak early to late diastolic transmitral flow velocity (r = -0.37, P < .05), the deceleration time from peak to baseline of the early diastolic transmitral flow velocity (r = 0.57, P < .01), the peak early diastolic mitral annular motion velocity (r = -0.41, P < .05), and the peak early diastolic strain rates at the endocardial sites of the LV posterior and inferior walls (r = 0.61, P < .001; r = 0.56, P < .001, respectively). There were no relationships between CAVI and LV ejection fraction, peak systolic mitral annular motion velocity, or peak systolic strain rates of the LV walls. Multiple regression analysis revealed that the early diastolic strain rates at the endocardial sites of the LV walls are strongly correlated with CAVI. There were no relationships between the IMT and the LV systolic and diastolic parameters. CONCLUSION: These results suggest that cardiovascular risk factors interact to affect arterial stiffness and LV relaxation, and therefore support the importance of screening using CAVI and ultrasonic strain imaging and early intervention in this patient population.