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.

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 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.

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.

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.

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.

Activation of RhoA and inhibition of myosin phosphatase as important components in hypertension in vascular smooth muscle.

Two mechanisms are proposed to account for the inhibition of myosin phosphatase (MP) involved in Ca2+ sensitization of vascular muscle, ie, phosphorylation of either MYPT1, a target subunit of MP or CPI-17, an inhibitory phosphoprotein. In cultured vascular aorta smooth muscle cells (VSMCs), stimulation with angiotensin II activated RhoA, and this was blocked by pretreatment with 8-bromo-cGMP. VSMCs stimulated by angiotensin II, endothelin-1, or U-46619 significantly increased the phosphorylation levels of both MYPT1 (at Thr696) and CPI-17 (at Thr38). The angiotensin II-induced phosphorylation of MYPT1 was completely blocked by 8-bromo-cGMP or Y-27632 (a Rho-kinase inhibitor), but not by GF109203X (a PKC inhibitor). In contrast, phosphorylation of CPI-17 was inhibited only by GF109203X. Y-27632 dramatically corrected the hypertension in N(omega)-nitro-L-arginine methyl ester (L-NAME)-treated rats, and this hypertension also was sensitive to isosorbide mononitrate. The level of the active form of RhoA was significantly higher in aortas from L-NAME-treated rats. Expression of RhoA, Rho-kinase, MYPT1, CPI-17, and myosin light chain kinase were not significantly different in aortas from L-NAME-treated and control rats. Activation of RhoA without changes in levels of other signaling molecules were observed in three other rat models of hypertension, ie, stroke-prone spontaneously hypertensive rats, renal hypertensive rats, and DOCA-salt rats. These results suggest that independent of the cause of hypertension, a common point in downstream signaling and a critical component of hypertension is activation of RhoA and subsequent activation of Rho-kinase.

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.

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.

Triggers of acute pulmonary thromboembolism developed in hospital, with focusing on toilet activities as triggering acts.

BACKGROUND: The recognition of the trigger which is the action leading to the occurrence of acute pulmonary thromboembolism (APTE) is important to perform early diagnosis and early management of APTE. METHODS AND RESULTS: The trigger of APTE in 138 patients who developed APTE in hospital was investigated. The triggers of APTE were specified in 57 patients. Approximately half of these patients developed APTE during toilet activities (defecation and micturition). Mortality of the patients with APTE associated with toilet activities was 33%. APTE associated with toilet activities was independently related to a recent major surgery, heart diseases and a recent angiography. CONCLUSIONS: Defecation and micturition would be common triggers of APTE after operation and angiography, especially in patients with cardiac dysfunction.

A case of acute myocardial infarction caused by left main trunk disease with dilated cardiomyopathy.

A case of acute myocardial infarction caused by left main trunk disease with dilated cardiomyopathy is presented. Cardiac MRI findings may suggest the etiology of left ventricular dysfunction in this case is idiopathic dilated cardiomyopathy, which associated with acute myocardial infarction caused by left main trunk disease.

Assessment by radionuclide ventriculography of postischemic regional left ventricular dysfunction in patients with healed myocardial infarction or angina pectoris.

Postischemic left ventricular (LV) dysfunction has been observed in experimental animal models after brief, complete coronary artery occlusion followed by reperfusion, but less relevant information is available for humans. The incidence and duration of postischemic LV dysfunction was examined by exercise radionuclide ventriculography in 50 patients with coronary artery disease. Cardiac imaging was performed at rest and was repeated during exercise and then immediately after and 5, 10, and 20 minutes after exercise. LV regional wall motion abnormalities were noted in 50 segments during exercise; they persisted in 30 of 50 segments after exercise, and remained apparent for 20 minutes in 11 segments. In contrast, in 33 segments, wall motion abnormalities were noted only after exercise and continued for 20 minutes in 13 of 33 segments. Exercise-related wall motion abnormalities were observed in 63 segments (76%) after exercise, and in 24 of 63 segments abnormalities continued for 20 minutes after exercise, although parameters of LV hemodynamic functions approached normal values after exercise. The mechanism of postexercise dysfunction is considered to involve acute myocardial stunning after a brief episode of myocardial ischemia, whereas regional wall motion abnormalities observed only after exercise seem to be related to increased levels of catecholamines or sympathetic overdrive, which mask less significant myocardial ischemia during exercise.

RhoA activation in vascular smooth muscle cells from stroke-prone spontaneously hypertensive rats.

RhoA is commonly activated in the aorta in various hypertensive models, indicating that RhoA seems to be a molecular switch in hypertension. The molecular mechanisms for RhoA activation in stroke-prone spontaneously hypertensive rats (SHRSP) were here investigated using cultured aortic smooth muscle cells (VSMC). The level of the active form of RhoA was higher in VSMC from SHRSP than in those from Wistar-Kyoto rats (WKY). The phosphorylation level of myosin phosphatase target subunit 1 (MYPT1) at the inhibitory site was also significantly higher in SHRSP, and the phosphorylation levels in both VSMCs were strongly inhibited to a similar extent by treatment with Y-27632, a Rho-kinase inhibitor. The expression levels of RhoA/Rho-kinase related molecules, namely RhoA, Rho-kinase, MYPT1, CPI-17 (inhibitory phosphoprotein for myosin phosphatase) and myosin light chain kinase, were not different between SHRSP and WKY. Valsartan, an angiotensin II (Ang II)- type 1 receptor antagonist, selectively and significantly reduced the RhoA activation in VSMC from SHRSP. The expression levels of the Rho GDP-dissociation inhibitor (RhoGDI) and leukemia-associated Rho-specific guanine nucleotide exchange factor (RhoGEF) did not differ between SHRSP and WKY. In cyclic nucleotide signaling, cyclic GMP (cGMP)-dependent protein kinase Ialpha (cGKIalpha) was significantly downregulated in SHRSP cells, although there were no changes in the expression levels of guanylate cyclase beta and cyclic AMP (cAMP)-dependent protein kinase or the intracellular contents of cGMP and cAMP between the two rat models. These results suggest that the possible mechanisms underlying RhoA activation in VSMC from SHRSP are autocrine/paracrine regulation by Ang II and/or cGKIalpha downregulation.

Bilateral giant coronary aneurysms diagnosed non-invasively by dynamic magnetic resonance imaging.

Giant coronary aneurysms are sometimes misdiagnosed as cardiac tumors when they are filled with thrombus. In this case, dynamic magnetic resonance imaging revealed the coronary artery and cardiac mass, and was the most useful tool for diagnosis of giant coronary aneurysms non-invasively.

Effective cardiac resynchronization after Dor procedure and mitral annuloplasty.

Endoventricular circular patch plasty (Dor ventriculoplasty) is an effective strategy for severely impaired left ventricular function due to ischemic cardiomyopathy. Cardiac resynchronization therapy improves cardiac function in patients with severe congestive heart failure and an intraventricular conduction delay. The present case demonstrates the efficacy of adding cardiac resynchronization to Dor ventriculoplasty and mitral annuloplasty in a patient with severely impaired left ventricular function and an intraventricular conduction delay.

Intravascular hemolysis in aortic stenosis.

A 67-year-old woman with rheumatic aortic stenosis for 20 years was admitted to our hospital. Although she had no overt symptoms, she had severe aortic valve stenosis with a transvalvular pressure gradient of more than 150 mmHg. She had also been suffering from anemia and mild chronic renal failure. A peripheral blood smear showed numerous fragmented erythrocytes. Hemoglobin was 8.4 g/dl, lactate dehydrogenase was 316 IU/l, haptoglobin was less than 7.3 mg/dl, and hemosiderinuria was evident. We diagnosed intravascular hemolysis related to aortic stenosis. After we performed an aortic valve replacement, fragmentation on the peripheral blood smear dramatically disappeared.

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.