Echocardiographic Assessment of Cardiac Structural and Functional Abnormalities in Patients With End-Stage Renal Disease Receiving Chronic Hemodialysis.

BACKGROUND: The aim of this study was to assess the echocardiographic characteristics of chronic hemodialysis (HD) patients with end-stage renal disease (ESRD) in a multicenter prospective cohort study.Methods and Results:Three hundred and fifteen patients with ESRD (67.9±10.6 years, 47.6% male) on chronic HD for ≥1 year were examined on transthoracic echocardiography, including Doppler-derived aortic valve area (AVA) measurement. Only 11.5% and 3.4% of all patients had normal left ventricular (LV) geometry and normal LV filling pattern, respectively. The majority of patients had aortic and mitral valvular calcification, and approximately 50% of all 315 patients had aortic valve narrowing with AVA <2.0 cm2. Patients were divided into 3 groups according to AVA index tertile: group 1, highest tertile; group 2, middle tertile; and group 3, lowest tertile. Group 3 was older, had a greater cardiothoracic ratio on chest X-ray, higher plasma brain natriuretic peptide and total LV afterload, and lower stroke volume index than the other 2 groups. Age and intact parathyroid hormone (PTH) level were independently associated with low AVA index. CONCLUSIONS: Patients with ESRD on chronic HD have a high prevalence of cardiac structural and functional abnormalities including calcified aortic sclerosis. High age and PTH were associated with aortic valve narrowing in these patients.

Antialbuminuric effect of eplerenone in comparison to thiazide diuretics in patients with hypertension.

This study investigated the effects and safety of eplerenone or thiazide diuretics in patients with hypertension and albuminuria (pretreatment urinary albumin/creatinine ratio ≥10 mg/gCr) treated with an angiotensin II receptor blocker. The primary end point was the mean percent change in the urinary albumin/creatinine ratio from baseline to 48 weeks. An efficacy analysis was performed in 195 patients (98 in the eplerenone group and 97 in the thiazide group). Systolic and diastolic blood pressures at 48 weeks were similar in the two groups. The mean percent change in the urinary albumin/creatinine ratio from baseline to 48 weeks was similar in the two groups (P=.804). In the safety analysis, the withdrawal rates for adverse events were similar in both groups. The antialbuminuric effects and safety of eplerenone therapy were similar to those of thiazide diuretics when combined with an angiotensin II receptor blocker in patients with hypertension and albuminuria.

Use of psychotropics and the risk of falls in hospitalized psychiatric patients.

As hospitalized patients in psychiatry departments are often prescribed multiple psychotropics depending on their psychiatric symptoms, psychotropics are considered as important factors potentially associated with a high risk of falls. In this study, we attempted to investigate, from the aspect of drug prescription, to what degree the number and doses of psychotropics must be adjusted in order to reduce risk of falls in hospitalized psychiatric patients. The subjects were 526 patients, consisting of a fall group of 313 patients, who had experienced 1 to 5 falls (510 events) and a control group of 213 patients who had never experienced falls. Multiple logistic regression analysis was performed to determine the correlations between the occurrence of falls and the number and doses of psychotropics. The results showed that the risk of falls increased with increasing number of antipsychotics and anxiolytics/hypnotics prescribed, with the risk increasing, by 3.75-fold with the increase in the dose of chlorpromazine (CP)-equivalents to more than 600 mg, by 2.08-fold when the dose of diazepam (DAP)-equivalents to more than 15 mg, and by 7.80-fold with increase in CP-equivalents to more than 600 mg concomitantly with an increase in DAP-equivalents to more than 15 mg. In addition, a tendency towards increase in the frequency of falls was observed when more than 5 psychotropics were prescribed concomitantly. The above results suggested that the risk of falls may be reduced by appropriately adjusting the number of drugs and the doses of psychotropics used in the treatment of psychiatric disorders.

Kidney-protective effects of azelnidipine versus a diuretic in combination with olmesartan in hypertensive patients with diabetes and albuminuria: a randomized study.

BACKGROUND: A thiazide diuretic used in combination with benazepril is superior to amlodipine plus benazepril in reducing albuminuria in hypertensive patients with diabetes. However, calcium channel blockers have diverse characteristics. Thus, we investigated whether combining an angiotensin receptor blocker with either azelnidipine or a thiazide diuretic produced similar reductions in albuminuria in hypertensive diabetic patients for the same levels of blood pressure achieved. METHODS: Hypertensive patients with type 2 diabetes and albuminuria (30-600 mg/g creatinine) under antihypertensive treatment (mean age 67.0±7.6 years) were instructed to stop all antihypertensive treatment and take a combination of olmesartan (20 mg/day) and amlodipine (5 mg/day) for 3 months (run-in period). Then, patients were randomly assigned to receive either olmesartan plus azelnidipine (16 mg/day; n=71) or olmesartan plus trichlormethiazide (1 mg/day; n=72) for an additional 6 months. The primary end point was urinary excretion of albumin at 6 months after randomization. RESULTS: At the time of randomization, urinary albumin was 116.0 and 107.8 mg/g creatinine (geometric mean) in the azelnidipine and diuretic arms, respectively, and was reduced to a similar extent [79.8 (95% confidence interval 66.4-96.0) and 89.7 (74.6-107.7) mg/g creatinine, respectively, after adjustment for baseline values]. Blood pressure did not differ between the two groups throughout the study period. CONCLUSIONS: Azelnidipine is equally effective as a thiazide diuretic in reducing urinary albumin when used in combination with olmesartan.

Surgical management of colorectal cancer in patients with psychiatric disorders.

PURPOSE: We analyzed the surgical data and evaluated the management of colorectal cancer (CRC) in patients with psychiatric disorders. METHODS: We reviewed the medical records of 83 patients who underwent elective surgery for CRC and divided them into a psychiatric disorder group and a control group to compare the operative data and available clinical information. RESULTS: Of the 83 patients, 27 had psychiatric disorders. The most characteristic symptom of CRC was bloody stool in the psychiatric disorder group, and occult blood in the control group. Postoperative pneumonia occurred significantly more often in the psychiatric group (14.8% vs 1.8%, P = 0.019). Patients with a psychiatric disorder needed significantly more psychotropic drugs (70.4% vs 7.1%, P < 0.001), more physical restraint (44.4% vs 12.5%, P = 0.001), and exhibited more resistant behavior (51.9% vs 8.9%, P < 0.001) postoperatively than the controls. Moreover, a significant decrease in serum albumin (Alb) and total protein (TP) was seen in the psychiatric disorder group on postoperative days (PODs) 21 and 28. A psychiatric disorder was a significant predictive factor for a decrease in TP (odds ratio [OR] 24.2) and Alb (OR 8.6). CONCLUSIONS: Insufficient nutrition in the psychiatric disorder group was not attributable solely to the higher incidence of postoperative complications. As psychiatric disorders compromise nutrition, integral treatment provided by surgeons and psychiatrists would improve the nutritional status of these patients and reduce the incidence of postoperative morbidity.

Patients with a hypertensive response to exercise have impaired left ventricular diastolic function.

An exaggerated increase in systolic blood pressure prolongs myocardial relaxation and increases left ventricular (LV) chamber stiffness, resulting in an increase in LV filling pressure. We hypothesize that patients with a marked hypertensive response to exercise (HRE) have LV diastolic dysfunction leading to exercise intolerance, even in the absence of resting hypertension. We recruited 129 subjects (age 63+/-9 years, 64% male) with a preserved ejection fraction and a negative stress test. HRE was evaluated at the end of a 6-min exercise test using the modified Bruce protocol. Patients were categorized into three groups: a group without HRE and without resting hypertension (control group; n=30), a group with HRE but without resting hypertension (HRE group; n=25), and a group with both HRE and resting hypertension (HTN group; n=74). Conventional Doppler and tissue Doppler imaging were performed at rest. After 6-min exercise tests, systolic blood pressure increased in the HRE and HTN groups, compared with the control group (226+/-17 mmHg, 226+/-17 mmHg, and 180+/-15 mmHg, respectively, p<0.001). There were no significant differences in LV ejection fraction, LV end-diastolic diameter, and early mitral inflow velocity among the three groups. However, early diastolic mitral annular velocity (E') was significantly lower and the ratio of early diastolic mitral inflow velocity (E) to E' (E/E') was significantly higher in patients of the HRE and HTN groups compared to controls (E': 5.9+/-1.6 cm/s, 5.9+/-1.7 cm/s, 8.0+/-1.9 cm/s, respectively, p<0.05). In conclusion, irrespective of the presence of resting hypertension, patients with hypertensive response to exercise had impaired LV longitudinal diastolic function and exercise intolerance.

The Günther-Tulip retrievable IVC filter: clinical experience in 118 consecutive patients.

BACKGROUND: The purpose of this study was to assess the use of the Günther Tulip Filter (GTF) for the management of venous thromboembolism (VTE). METHODS AND RESULTS: Between December 2000 and April 2005, 118 patients (42 males, 76 females; mean age 60.5 years) diagnosed with VTE, underwent treatment with a GTF. The filter was left permanently in 52 patients. In the other 66 patients, attempts were made to retrieve it, with success in 60 cases (90.9%). No major complication was found throughout the filter's use. Of the 58 patients with the permanent filters, 41 underwent enhanced computed tomography at follow-up in the chronic phase. Thirty-eight filters (92.7%) remained patent, and under low-intensity anticoagulation therapy (international normalized ratio 1.8+/-0.4), the patency rate was 97.1%. Penetration of the inferior vena cava (IVC) wall by the filter's struts beyond a distance of 3 mm occurred in 23 patients (56.1%), but there was no observable leakage from the IVC or injury to adjacent organs. CONCLUSIONS: The GTF is feasible and safe for treating VTE. When used permanently, GTFs have a high patency rate, and there is neither leakage from the IVC nor injury to adjacent organs in the event of penetration by the struts.

Improvement of left ventricular mechanical dyssynchrony associated with restoration of left ventricular function in a patient with fulminant myocarditis and complete left bundle branch block.

A 52-year-old woman with fulminant myocarditis had completed left bundle branch block (LBBB) and severely impaired left ventricular (LV) function. Marked mechanical dyssynchrony with septal-to-posterior delay of 389 ms was observed by echocardiographic speckle tracking radial strain imaging on admission, which was dramatically improved to 106 ms after total recovery from acute myocarditis with restoration of LV ejection fraction whereas her electrocardiogram still showed complete LBBB.

Two cases of dilated cardiomyopathy with right ventricular wall degeneration demonstrated by late gadolinium enhanced MRI.

Right heart failure is prominent in some patients with dilated cardiomyopathy (DCM). In this article, we present right ventricular wall degeneration and fibrosis demonstrated by late gadolinium enhanced magnetic resonance imaging (MRI) in patients with DCM.

High glucose induces plasminogen activator inhibitor-1 expression through Rho/Rho-kinase-mediated NF-kappaB activation in bovine aortic endothelial cells.

Recently, it has become evident that elevated levels of plasminogen activator inhibitor-1 (PAI-1) are associated with myocardial infarction and stroke, especially in patients with diabetes. The molecular mechanisms involved in hyperglycemia-induced PAI-1 expression in bovine aortic endothelial cells (BAEC) were investigated. PAI-1 expression in BAEC was significantly increased in accordance with the concentration of glucose in media from 5.7 mM to 23 mM. Stimulation with high glucose (23 mM) significantly increased small GTPase Rho A activation. Pretreatment with a Rho-kinase inhibitor, Y-27632 (1-10 microM), significantly blocked high glucose-induced PAI-1 expression. NF-kappaB activity determined using the luciferase reporter gene assay was significantly enhanced by high glucose, and pretreatment with Y-27632 inhibited high glucose-induced PAI-1 expression at the basal level. An inhibitor of NF-kappaB action, namely parthenolide (0.1 microM), BAY 11-7082 (5 microM) and SN50 (1 microM), significantly blocked high glucose-mediated PAI-1 expression to a level with low glucose (5.7 mM). These data suggested that high glucose-induced PAI-1 expression in endothelial cells is mediated by NF-kappaB activation through the Rho/Rho-kinase pathway. Inhibition of Rho/Rho-kinase signaling might be a novel target for diabetes and metabolic syndrome.

Impact of heart rate on mechanical dyssynchrony and left ventricular contractility in patients with heart failure and normal QRS duration.

AIMS: The quantification of mechanical dyssynchrony has important diagnostic value and may help to determine optimal therapy in heart failure (HF). We hypothesized that mechanical dyssynchrony may be augmented at increased heart rates in patients with HF and normal QRS duration. METHODS AND RESULTS: From online segmental conductance catheter signals, we derived indices to quantify temporal and spatial aspects of mechanical dyssynchrony during systole in 20 control subjects, 20 HF patients with normal QRS duration, and 12 HF patients with complete left bundle branch block (CLBBB). Data were collected at baseline, and then following a 40 bpm increase in heart rate induced by right atrial pacing. Mechanical dyssynchrony in HF patients with normal QRS duration or CLBBB was higher than that found in control subjects. In HF patients with normal QRS duration, mechanical dyssynchrony increased from 37.4+/-4.8% at baseline to 43.2+/-4.4% with increased heart rate (p<0.01), the resultant degree of mechanical dyssynchrony was similar to that at baseline in the HF patients with CLBBB. Increased heart rate did not affect dyssynchrony in the control patients. CONCLUSION: Mechanical dyssynchrony was augmented as heart rate increased by right atrial pacing in patients with HF and normal QRS duration.

The relationship between aortic augmentation index and pulse wave velocity: an invasive study.

OBJECTIVES: The aortic augmentation index (AI) and aortic pulse wave velocity (PWV) are known to be indicators of arterial stiffness. However, it is not clear whether aortic AI and PWV reflect aortic stiffness in similar ways. We investigated the relationship between aortic AI and PWV by measuring them directly using a catheter technique. DESIGN AND METHODS: Forty-one patients, aged 34-79 years, were studied during diagnostic cardiac catheterization. Aortic pressures were measured using a catheter-tip manometer at two points, one in the ascending aorta and one 40 cm distally in the descending aorta. Aortic AI was defined as the difference between early and late pressure peaks divided by the pulse pressure of the ascending aorta. Aortic PWV was calculated as the distance between the two measuring sites divided by the transit time. We also examined the effects of vasodilatation on AI and PWV by the intra-aortic administration of nitroglycerin in 15 patients. RESULTS: AI was significantly related to age, systolic aortic pressure, heart rate, left ventricular ejection time, and height. Aortic PWV showed an association only with age and systolic aortic pressure. There was no significant relationship between aortic AI and PWV (r = 0.28, NS). Nitroglycerin also produced different effects on aortic AI and PWV: aortic AI was significantly decreased (-0.17, P < 0.01) after nitroglycerin, but PWV remained unchanged (+0.4 m/s, NS). CONCLUSIONS: Aortic AI and PWV cannot be used interchangeably as an index of arterial stiffness. AI may not be a true indicator of arterial stiffness, but an index of wave reflection including PWV.

Antique SVG with two humps: a case of two giant aneurysms of single saphenous vein bypass graft.

Saphenous vein graft aneurysms are a rare complication of coronary artery bypass surgery. In this article, we present a 3-dimensional computed tomography image of two giant aneurysms of a single saphenous vein bypass graft.

Characterization and function of MYPT2, a target subunit of myosin phosphatase in heart.

Characterization of cardiac MYPT2 (an isoform of the smooth muscle phosphatase [MP] target subunit, MYPT1) is described. Several features of MYPT2 and MYPT1 were similar, including: a specific interaction with the catalytic subunit of type 1 phosphatase, delta isoform (PP1cdelta); interaction of MYPT2 with the small heart-specific MP subunit; interaction of the C-terminal region of MYPT2 with the active form of RhoA; phosphorylation by Rho-kinase at an inhibitory site, Thr646 and thiophosphorylation at Thr646 inhibited activity of the MYPT2-PP1cdelta complex. MYPT2 activated PP1cdelta activity, using light chains from smooth and cardiac muscle, by reducing K(m) and increasing k(cat). The extent of activation (k(cat)) was greater than for MYPT1 and could reflect distinct N-terminal sequences in the two MYPT isoforms. Adenovirus-mediated gene transfer of MYPT2 and PP1cdelta reduced the phosphorylation level of cardiac light chains following stimulation with A23187. Overexpression of MYPT2 and PP1cdelta blocked the angiotensin II-induced sarcomere organization in cultured cardiomyocytes. Electron microscopy indicated locations of MYPTs, at, or close to, the Z-line, the A band and mitochondria. Similarity of the two MYPT isoforms suggests common enzymatic mechanisms and regulation. Cardiac myosin is a substrate for the MYPT2 holoenzyme, but the Z-line location raises the possibility of other substrates.

Beneficial acute effects of rho-kinase inhibitor in patients with pulmonary arterial hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a poor prognostic disease with limited treatment options. Rho-kinase is involved in the pathophysiology of several diseases underlying smooth muscle hypercontraction, so the purpose of this study was to investigate the efficacy of fasudil, a Rho-kinase inhibitor, in patients with PAH. METHODS AND RESULTS: Fasudil 30 mg was intravenously injected over 30 min in 8 patients (all female, mean +/- SD, 41+/-11 years) with PAH. The lowest total pulmonary resistance (TPR) time was within 30-60 min after administration. Administration of fasudil decreased TPR from 1,069+/-573 dyne . s . cm (-5) to 809+/-416 dyne . s . cm(-5) (p<0.005) and mean pulmonary arterial pressure from 41.3+/-12.8 mmHg to 37.9+/-14.6 mmHg (p<0.05). The cardiac index was increased from 2.42+/-0.73 L . min(-1) . m(-2) to 2.84+/-0.79 L . min(-1) . m(-2) (p<0.02). Systemic vascular resistance and systolic systemic arterial pressure (SAP) were decreased (p<0.005, p=0.09, respectively), but the decrease in SAP was small (-6.4+/-9.1 mmHg). CONCLUSION: These results suggest that Rho-kinase is involved in the pathogenesis of human PAH and that fasudil is a novel therapeutic agent.

Effects of human atrial natriuretic peptide on cardiac function and hemodynamics in patients with high plasma BNP levels.

Both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) bind preferentially to the natriuretic peptide A receptor. Therefore, we hypothesized that the positive inotropic and lusitropic effects of ANP might be blunted in patients with moderate congestive heart failure and high BNP levels. Micromanometers and conductance catheters were used to obtain relatively load-insensitive left ventricular pressure-volume analysis in order to compare the myocardial and load-altering actions of ANP in 20 patients with low and high plasma BNP levels. In the low-BNP group (plasma BNP levels <230 pg/ml), ANP infusion significantly decreased end-systolic pressure and end-diastolic pressure and volume, increased end-systolic elastance, and shortened left ventricular relaxation. By contrast, in the high-BNP group (plasma BNP levels >230 pg/ml), the effect of ANP infusion on LV contractility was blunted but its beneficial effects on LV diastolic function and LV-arterial coupling remained. Thus, ANP infusion may improve LV diastolic function even in patients with moderate heart failure and high plasma BNP levels.

Rho/Rho-kinase pathway contributes to C-reactive protein-induced plasminogen activator inhibitor-1 expression in endothelial cells.

OBJECTIVE: Rho/Rho-kinase pathway plays pivotal roles in cardiovascular diseases including arteriosclerosis and hypertension. Recently it has become evident that C-reactive protein (CRP), a powerful marker for cardiovascular events, has direct proatherothrombotic effects on vascular cells. However, its molecular mechanism has not been fully investigated. We examined the involvement of Rho/Rho-kinase signaling in CRP-induced plasminogen activator inhibitor-1 (PAI-1) expression in bovine aortic endothelial cells (BAECs). METHODS AND RESULTS: PAI-1 expression was determined by Western blotting. RhoA activation was determined by an affinity pull-down assay using Rho-binding fragment of rhotekin. NF-kappaB activity was determined using the luciferase reporter gene. Incubation of BAECs with human recombinant CRP (> or =25 microg/mL) induced a significant increase in PAI-1 expression. Stimulation of BAECs with CRP significantly increased RhoA activation. Pretreatment with TAT-C3 (a membrane-permeable RhoA inhibitor) and Y-27632 (Rho-kinase inhibitor) significantly inhibited CRP-induced PAI-1 expression. NF-kappaB activity was markedly enhanced by CRP and pretreatment with Y-27632 inhibited its activation. Parthenolide, SN50, and BAY 11-7082 (NF-kappaB inhibitors) significantly blocked CRP-mediated PAI-1 expression. CONCLUSIONS: These data suggested that CRP activates Rho/Rho-kinase signaling, which in turn activates NF-kappaB activity, resulting in PAI-1 expression in BAEC. These observations provide evidence for the possible involvement of Rho/Rho-kinase signaling in CRP-induced atherothrombogenesis.