Virtual Reality-Guided Simulation for Percutaneous Coronary Intervention in a Patient with Anatomical Anomalies: A Case Report.

BACKGROUND Virtual reality (VR)-guided GC simulation for patients with anatomical anomalies using cardiac computed tomography (CT) has been recently reported. Rotational atherectomy (RA) for the left circumflex (LCX) ostium is challenging due to the tortuous anatomy, acute angulation, and variable vessel size compared to other lesions. The appropriate positioning and coaxiality of the guide catheter (GC) are key factors for safely performing RA. It would be beneficial if it could be simulated prior to percutaneous coronary intervention (PCI). CASE REPORT We treated a 55-year-old man with angina. We performed coronary angiography and detected an ostial calcified lesion of the LCX. We needed RA for this lesion, but PCI was very difficult and challenging. CT revealed right-sided aortic arch with stenosis of left subclavian artery from the Kommerell diverticulum at the distal part of the aortic arch. Therefore, the approach site for PCI was limited. We simulated the appropriate guide catheter and approach site for PCI by VR. PCI was successfully performed with RA, as in the VR simulation. CONCLUSIONS We successfully performed PCI for an ostial calcified lesion of the LCX in a patient with a right-sided aortic arch. Use of VR-guided GC simulation is a useful new option that can help visualize the anatomy and ensure safe procedures for complex lesions.

One-Year Outcome of Drug-Coated Balloon vs. Drug-Eluting Stent in Patients Undergoing Initial Percutaneous Coronary Intervention (PCI) for De Novo Lesion.

BACKGROUND: Drug-eluting stents (DES) are the major treatment option in percutaneous coronary intervention (PCI). Recently, drug-coated balloon (DCB) utilization has been increasing globally, leading to the expected new strategy of "stent-less PCI." This study aimed to evaluate the one-year outcome of DCB compared to DES. METHODS: Patients who underwent initial PCI for de novo lesions in our institution from January 2018 to December 2021 (n=337) were subjected to retrospective analysis. Among them, 75 patients were treated with DCB, while 262 patients were treated with DES. Target lesion failure (TLF) was evaluated during the follow-up period. RESULTS: The proportion of PCIs for ACS was significantly lower in the DCB group (DCB, n=23, 30.7% vs. DES, n=143, 54.6%; p=0.001). The median device diameter and length in the DES group were larger than those in the DCB group (DCB, 2.60 mm vs. DES, 2.98 mm; p<0.001; DCB, 19.1 mm vs. DES, 25.2 mm; p<0.001). There was no significant difference between the DCB and DES groups in lesion calcification. The proportion of ostial lesions was significantly higher in the DCB group (DCB, n=13, 17.3% vs. DES, n=21, 8.0%; p=0.018). The cumulative rate of TLF (DCB, n=5, 6.7% vs. DES, n=18, 6.9%; p=0.951) did not significantly differ between the DCB and DES groups. CONCLUSION: DCB may be as effective a strategy as DES in the patient who underwent initial PCI for a de novo lesion.

A 0.8-cm clear cell neuroendocrine tumor G1 of the gallbladder with lymph node metastasis: a case report.

BACKGROUND: Neuroendocrine tumors (NETs) of the gallbladder are rare and generally considered low-grade malignancies. We herein describe a case of a patient with a 0.8-cm clear cell NET G1 of the gallbladder with nodal involvement. CASE PRESENTATION: A 65-year-old man with no medical history indicative of von Hippel-Lindau (VHL) disease underwent laparoscopic cholecystectomy for cholecystolithiasis. There was a 0.8-cm tumor in the neck of the gallbladder. Histologic examination revealed nests or trabecular growth of clear cells with small round-to-oval nuclei. Immunohistochemically, tumor cells showed positivity for chromogranin A and synaptophysin; Ki-67 index was < 1.0%. Based on the World Health Organization 2010 classification, we made a diagnosis of clear cell variant of NET G1 without VHL disease. The tumor invaded the muscular layer and had no extension to the perimuscular connective tissue but had metastasized to a cystic duct node. A radical second resection with regional lymphadenectomy of the gallbladder was performed, and there was no metastasis on histology. After the definitive surgery, he was followed up for 10 months without adjuvant therapy and is alive and well with no evidence of recurrence. CONCLUSIONS: Our experience suggests that, even when smaller than 1 cm, NET G1 of the gallbladder can metastasize. When NET G1 is incidentally identified in the gallbladder of a surgical specimen, detailed pathologic examination of the cystic duct node, when found, should be performed to guide whether a radical second resection with regional lymphadenectomy is appropriate.

[A Case of Locally Advanced Neuroendocrine Carcinoma of the Stomach Could be Curably Resected after Chemotherapy with CPT-11/CDDP].

A 64-year-old man was admitted to our hospital because of epigastralgia. Gastrointestinal endoscopyrevealed a submucosal tumor with ulceration in the upper bodyof the stomach. The tumor was histologicallydiagnosed as a neuroendocrine carcinoma. CT showed that the tumor had directlyinfiltrated the pancreas and splenic vessels. The patient underwent onlyan exploratorylaparotomybecause the tumor seemed to involve the celiac artery. Chemotherapywas conducted using CPT-11/ CDDP. After 15 courses of chemotherapy, a significant tumor reduction was obtained. We performed total gastrectomy with D2 lymphadenectomy, distal pancreatectomy and splenectomy. Histopathological examination of surgical specimens showed that onlyfew carcinoma cells remained in the stomach and pancreas. Neoadjuvant chemotherapycan be a useful treatment for unresectable locallyadvanced neuroendocrine carcinoma of the stomach.

Rosuvastatin prevents aortic arch plaque progression and improves prognosis in ischemic stroke patients.

OBJECTIVES: Complicated aortic arch plaques (CAP) and their progression are important for recurrent ischemic stroke (IS) and its prognosis. We investigated the effects and clinical benefits of rosuvastatin therapy on this pathophysiology. The purpose of this study was to investigate whether rosuvastatin prevention of aortic arch plaque progression improved the prognosis of IS patients. METHODS: Ninety-seven consecutive acute cerebral embolism patients were retrospectively surveyed. All had transesophageal echocardiography (TEE) to assess the presence or absence of CAP, defined as aortic wall thickness ≥4 mm or plaque ulceration. Patients received conventional antithrombotic therapy as clinically indicated. All patients with CAP were recommended to receive 5 mg rosuvastatin/day, administered by their attending physicians; not all physicians followed this recommendation. Six-month follow-up TEEs were performed in patients with CAP who received rosuvastatin. Major adverse cerebrovascular events (MACEs) comprised recurrent IS and death. RESULTS: CAP was detected in 39 patients (40%), and MACEs in 15. Multivariate regression analysis showed that patients with CAP not taking rosuvastatin was an independent risk factor for MACEs (odds ratio = 18.044; 95% confidential interval = 2.089-155.846, p < 0.01). When patients were divided into three groups: those with CAP taking rosuvastatin, those with CAP not taking rosuvastatin, and those without CAP, Kaplan-Meier analysis demonstrated that patients with CAP not taking rosuvastatin had significantly more MACEs than those in the other two groups (long-rank test; χ2 = 6.553, p < 0.05). Six-month TEE follow-ups in the 26 patients with CAP taking rosuvastatin showed significant improvement in CAP diameter with improved lipid profiles; 88% (23/26 patients) showed no morphological CAP progression; 15 of these showed CAP regression. DISCUSSION: Rosuvastatin therapy prevented aortic arch plaque progression in IS patients with CAP, and may also have long-term clinical benefits.

Deficiency of Senescence Marker Protein 30 Exacerbates Cardiac Injury after Ischemia/Reperfusion.

Early myocardial reperfusion is an effective therapy but ischemia/reperfusion (I/R) causes lethal myocardial injury. The aging heart was reported to show greater cardiac damage after I/R injury than that observed in young hearts. Senescence marker protein 30 (SMP30), whose expression decreases with age, plays a role in reducing oxidative stress and apoptosis. However, the impact of SMP30 on myocardial I/R injury remains to be determined. In this study, the left anterior descending coronary artery was occluded for 30 min, followed by reperfusion in wild-type (WT) and SMP30 knockout (KO) mice. After I/R, cardiomyocyte apoptosis and the ratio of infarct area/area at risk were higher, left ventricular fractional shortening was lower, and reactive oxygen species (ROS) generation was enhanced in SMP30 KO mice. Moreover, the previously increased phosphorylation of GSK-3ß and Akt was lower in SMP30 KO mice than in WT mice. In cardiomyocytes, silencing of SMP30 expression attenuated Akt and GSK-3ß phosphorylation, and increased Bax to Bcl-2 ratio and cardiomyocyte apoptosis induced by hydrogen peroxide. These results suggested that SMP30 deficiency augments myocardial I/R injury through ROS generation and attenuation of Akt activation.

Anomalous Sinking of Spheres due to Local Fluidization of Apparently Fixed Powder Beds.

The sinking of an intruder sphere into a powder bed in the apparently fixed bed regime exhibits complex behavior in the sinking rate and the final depth when the sphere density is close to the powder bed density. Evidence is adduced that the intruder sphere locally fluidizes the apparently fixed powder bed, allowing the formation of voids and percolation bubbles that facilitates spheres to sink slower but deeper than expected. By adjusting the air injection rate and the sphere-to-powder bed density ratio, this phenomenon provides the basis of a sensitive large particle separation mechanism.

Deficiency of Long Pentraxin PTX3 Promoted Neointimal Hyperplasia after Vascular Injury.

AIM: Pentraxin 3 (PTX3) is a novel marker for the primary local activation of innate immunity and inflammatory responses. Although clinical and experimental evidence suggests that PTX3 is associated with atherosclerosis, the relationship between PTX3 and vascular remodeling after wall injury remains to be determined. We investigated the effects of PTX3 on neointimal hyperplasia following wire vascular injury. METHODS: PTX3 systemic knockout (PTX3-KO) mice and wild-type littermate (WT) mice were subjected to wire-mediated endovascular injury. At four weeks after wire-mediated injury, the areas of neointimal and medial hyperplasia were evaluated. RESULTS: The PTX3-KO mice exhibited higher hyperplasia/media ratios than the WT mice after wire injury, and the degree of Mac-3-positive macrophage accumulation was significantly higher in the PTX3-KO mice than in the WT mice. Furthermore, the PTX3-KO mice showed a much greater increase in the number of PCNA-stained cells in the vascular wall than that observed in the WT mice. CONCLUSIONS: A deficiency of PTX3 results in deteriorated neointimal hyperplasia after vascular injury via the effects of macrophage accumulation and vascular smooth muscle cell proliferation and migration.

Left atrial appendage dysfunction in acute cerebral embolism patients with sinus rhythm: correlation with pulse wave tissue Doppler imaging.

To evaluate left atrial appendage (LAA) dysfunction using left atrial pulse-wave tissue Doppler imaging (PW-TDI) in acute cerebral embolism (ACE) patients with sinus rhythm (SR), transthoracic (TTE) and transesophageal echocardiograhy (TEE) were performed in 60 consecutive patients with SR without obvious left ventricular dysfunction within 2 weeks after ACE. Two groups were identified: LAA dysfunction [LAA emptying peak flow velocity (LAA-eV) <0.55 m/s, n = 20, age 65 ± 10 years] and without LAA dysfunction (LAA-eV ≥ 0.55 m/s, n = 40, age 64 ± 10 years) on TEE. Left atrial wall motion velocity (WMV) was obtained from PW-TDI, with the sample volume placed at the left atrial anterior wall adjacent to ascending aortic inferior wall from the long axis view on TTE. WMVs showed triphasic waves: after the P wave (La') during systole (Ls'), and during early diastole. La' and Ls' were significantly lower in the group with versus without LAA dysfunction (4.9 ± 1.4 vs. 7.7 ± 1.8 cm/s, p < 0.0001; 5.3 ± 2.0 vs. 6.7 ± 1.9 cm/s, p < 0.001, respectively) and prevalence of paroxysmal atrial fibrillation, left atrial volume index, and serum levels of brain natriuretic peptide were significantly higher (60 vs. 15 %, p < 0.001; 32 ± 13 vs. 24 ± 13 ml/m(2), p < 0.05; 174 ± 279 vs. 48 ± 68 pg/ml, p < 0.01, respectively). La' was an independent predictor of LAA dysfunction (OR 0.380, 95 % CI 0.156-0.925, p < 0.05), and was significantly correlated with LAA-eV (r = 0.594, p < 0.0001) and LAA fractional area change (r = 0.682, p < 0.0001). The optimal cut-off value for LAA-eV < 0.55 m/s was 5.5 cm/s (sensitivity 83 %, specificity 88 %). La' is a useful and convenient strong predictor of LAA dysfunction in ACE patients with SR.

Rosuvastatin improves plaque morphology in cerebral embolism patients with normal low-density lipoprotein and severe aortic arch plaque.

The effect of rosuvastatin was investigated on complicated aortic arch plaque (CAP) morphology and lipid profiles in acute cerebral embolism (CE) patients with normal low-density lipoprotein-cholesterol (LDL-c) levels. Transesophageal echocardiography (TEE) studies were performed in 56 consecutive CE patients with LDL-c less than 140 mg/dL who were not taking lipid-lowering agents at baseline. CAP observed by TEE was defined as the presence of greater than 4-mm diameter, ulcerated, or mobile aortic plaque. Patients were divided into those with CAP versus without CAP (group A, n=24, age 69±8 years) and without CAP (group B, n=32, age 62±10 years). Of the 24 group A patients, 18 received 5 mg/d of rosuvastatin for 6 months and had follow-up TEE studies. In Group A, the baseline values of high-density lipoprotein-cholesterol (HDL-c) and apolipoprotein A-1 (ApoA-1) were significantly lower than in Group B (44±15 versus 55±15 mg/dL, P=.0059; 103±19 versus 137±25 mg/dL, P=.0006, respectively) and age and serum high-sensitivity C-reactive protein concentration were significantly higher (69±8 vs. 62±10 years, P=.0080; 2.34±3.05 vs. 0.67±1.00 mg/dL, P=.0054, respectively). By multivariate logistic regression analysis, ApoA-1 was shown to be an independent predictor of CAP (odds ratio=.894, 95% confidence intervals .800-.996, P=.0483). In the 18 group A patients receiving rosuvastatin for 6 months, aortic arch plaque diameter and serum LDL-c were significantly decreased (5.8±2.2 to 5.1±2.1 mm, P=.0377; 110±23 to 81±23 mg/dL, P=.0008, respectively), whereas serum HDL-c and ApoA-1 concentrations were significantly increased (42±8 to 52±9 mg/dL, P=.0002; 109±22 to 135±15 mg/dL, P=.0002, respectively). Plaques were morphologically improved in 11 patients, unchanged in 6, and worsened in 1. These data suggest that rosuvastatin improves plaque morphology concomitant with improving lipid profiles in CE patients with normal LDL-c levels.

Successful revascularization to right coronary artery by percutaneous coronary intervention after endovascular therapy for leriche syndrome.

A 69-year-old man with effort angina was admitted to our institution. Echocardiography showed poor left ventricular systolic function with akinesis of the anterior wall and severe hypokinesis of the inferior wall. We performed coronary angiography, which revealed two diseased vessels including chronic total occlusion in the left anterior descending artery and severe stenosis in the right coronary artery (RCA). In addition, aortography revealed aortoiliac occlusive disease known as Leriche syndrome. As the patient's symptom was stable, we first planned to perform endovascular therapy (EVT) for Leriche syndrome to make a route for intra-aortic balloon pumping. We prepared a bi-directional approach from bi-femoral arteries and a left brachial artery. The guidewire was passed through the occlusive area using the retrograde approach. The self-expanding stents were deployed by a kissing technique. At one week after EVT, a 6Fr sheath was inserted from the right radial artery and an intra-aortic balloon pump was successfully inserted through the right femoral artery for percutaneous coronary intervention (PCI) to the RCA. Two drug-eluting stents were successfully deployed to RCA after using an atherectomy device (rotablator). We reported the case as a successfully performed PCI to the RCA after EVT for Leriche syndrome.

Assessment of aortic arch stiffness using pulse-wave tissue Doppler imaging: a transesophageal echocardiographic comparison study of acute ischemic stroke patients and stroke-free patients.

BACKGROUND: Elevated aortic stiffness determined by transesophageal echocardiography (TEE), and presence of complicated aortic plaque provide prognostic information about cerebrovascular disease risk. Recently, pulse-wave tissue Doppler imaging (PW-TDI) has offered a new technique for assessing aortic wall stiffness. METHODS: The following aortic long-axis view TEE measurements were carried out in 103 consecutive acute ischemic stroke patients and 72 controls (stroke-free patients requiring TEE for conditions such as atrial fibrillation and valvular heart disease): (a) PW-TDI motion velocities measured as expansion peak velocity during systole (Vs) and contraction peak velocity during diastole (Vd); (b) aortic arch stiffness parameter ß (Aoß), defined as ß = ln (systolic blood pressure/diastolic blood pressure)/([Dmax - Dmin]/Dmin), where ln is the natural logarithm, Dmax is maximum aortic lumen diameter, and Dmin is minimum aortic lumen diameter. The PW-TDI of Vs and Vd was compared with conventional vessel parameters brachial-ankle pulse wave velocity (baPWV) and cardio-ankle vascular index (CAVI, calculated from blood pressure and PWV). RESULTS: Comparing acute ischemic stroke patients versus controls, Vs and Vd were significantly decreased (3.3 ± 1.6 vs. 3.9 ± 2.0 cm/sec, P < 0.05; 1.7 ± 0.6 vs. 2.1 ± 0.8 cm/sec, P < 0.01, respectively), and Aoß and aortic arch intima-media thickness (AoIMT) were significantly increased (15.3 ± 12.5 vs. 11.6 ± 6.5, P < 0.05; 3.2 ± 2.5 vs. 2.4 ± 2.1 mm, P < 0.05; respectively). Furthermore, Vs and Vd were significantly negatively correlated with age, Aoß, AoIMT, CAVI, and baPWV in all cases. CONCLUSIONS: The use of aortic arch wall PW-TDI for Vs and Vd evaluation constitutes an easily and readily assessed parameter for evaluating aortic arch stiffness.

Diacylglycerol kinase α exacerbates cardiac injury after ischemia/reperfusion.

Early coronary reperfusion of the ischemic myocardium is a desired therapeutic goal for the preservation of myocardial function. However, reperfusion itself causes additional myocardium injuries. Activation of the diacylglycerol-protein kinase C (DAG-PKC) cascade has been implicated in the cardioprotective effects occurring after ischemia/reperfusion (I/R). DAG kinase (DGK) controls cellular DAG levels by converting DAG to phosphatidic acid, and may act as an endogenous regulator of DAG-PKC signaling. In the present study, we examined the functional role of DGKα in cardiac injury after I/R in in vivo mouse hearts. We generated transgenic mice with cardiac-specific overexpression of DGKα (DGKα-TG). The left anterior descending coronary artery was transiently occluded for 20 min and reperfused for 24 h in DGKα-TG mice and wild-type littermate (WT) mice. The levels of phosphorylation activity of PKCε, extracellular-signal regulated kinase (ERK) 1/2, and p70 ribosomal S6 kinase (p70S6K) were increased after I/R in WT mouse hearts. However, in DGKα-TG mice, activation of PKCε, ERK1/2, and p70S6K was attenuated compared to WT mice. After 24 h, Evans blue/triphenyltetrazolium chloride double staining and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining showed that DGKα-TG mice had significantly larger myocardial infarctions and larger numbers of TUNEL-positive cardiomyocytes than WT mice. Echocardiography and cardiac catheterization revealed that left ventricular systolic function was more severely depressed in DGKα-TG mice than in WT mice after I/R. These findings suggest that DGKα exacerbates I/R injury by inhibiting the cardioprotective effects of PKCε, ERK1/2, and p70S6K activation.

Atrial endothelial impairment through Toll-like receptor 4 signaling causes atrial thrombogenesis.

Low-grade inflammation associated with heart failure (HF) is known to deteriorate cardioembolic stroke in patients with atrial fibrillation (AF). Little is known about the relationship between atrial endothelial impairment induced by innate immunity and thrombus formation. We examined whether atrial endothelial impairment through Toll-like receptor (TLR) 4 signaling causes atrial thrombogenesis. TLR4, heat shock protein 60, and vascular cell adhesion molecule (VCAM)-1 expression were higher in the atrium of AF patients who underwent valve replacement surgery with HF compared with those without it (p < 0.05). We created thoracic transverse aortic constriction (TAC) in TLR4 knock-out (KO) and wild-type (WT) mice. Atrial thrombosis was observed less frequently in TLR4 KO mice (4/15) than in WT mice (16/20) 4 weeks after TAC despite similar severity of heart failure. The decrease in endothelial nitric oxide synthase (eNOS) phosphorylation and increase in VCAM-1 and plasminogen activator inhibitor (PAI)-1 expression, observed in the atrium of WT mice following TAC, were significantly attenuated in TLR4 KO mice (p < 0.05). Nuclear factor-κB (NF-κB) activation after TAC was attenuated in TLR4 KO mice compared with WT mice. Activation of mitogen-activated protein kinase p38 (p38) after TAC was also attenuated in TLR4 KO mice (p < 0.05). Thus, increased VCAM-1 and PAI-1, and decreased eNOS phosphorylation through the TLR4/NFκB/p38 pathway, may be associated with atrial thrombogenesis in the heart failure mice model. Atrial endothelial impairment through the TLR4 signaling may play a role in atrial thrombogenesis in AF patients with HF.

Long pentraxin PTX3 exacerbates pressure overload-induced left ventricular dysfunction.

BACKGROUND: Left ventricular hypertrophy is enhanced by an inflammatory state and stimulation of various cytokines. Pentraxin 3 (PTX3) is rapidly produced in response to inflammatory signals, and high plasma PTX3 levels are seen in patients with heart failure. This study aimed to examine the influence of PTX3 on cardiac hypertrophy and left ventricular dysfunction with respect to pressure overload. METHODS AND RESULTS: PTX3 systemic knockout (PTX3-KO) mice, transgenic mice with cardiac-specific overexpression of PTX3 (PTX3-TG), and the respective wild-type (WT) littermate mice were subjected to transverse aortic constriction (TAC) or a sham operation. Cardiac PTX3 expression increased after TAC in WT mice. In vitro, hydrogen peroxide induced the expression of PTX3 in both cardiac myocytes and cardiac fibroblasts. Recombinant PTX3 phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) in cardiac fibroblasts. Phosphorylation of cardiac ERK1/2 and nuclear factor kappa-B after TAC was attenuated in the PTX3-KO mice but was enhanced in the PTX3-TG mice compared with WT mice. Interleukin-6 and connective tissue growth factor production was lower in the PTX3-KO mice than in the WT mice, but this was augmented in the PTX3-TG mice than in the WT mice. Echocardiography revealed that adverse remodeling with left ventricular dysfunction, as well as with increased interstitial fibrosis, was enhanced in PTX3-TG mice, while these responses were suppressed in PTX3-KO mice. CONCLUSION: The local inflammatory mediator PTX3 directly modulates the hypertrophic response and ventricular dysfunction following an increased afterload.

Usefulness of albuminuria as a prognostic indicator in patients with chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

Albuminuria is an established risk factor for mortality and cardiovascular events in the general population. Albuminuria might be a marker of the various pathophysiologic changes, such as diffuse vascular injury and systemic inflammation, that arise in patients with chronic heart failure (CHF). However, the relation between albuminuria and CHF has not yet been fully elucidated. Therefore, the purpose of the present study was to assess the prevalence and prognostic significance of albuminuria in patients with CHF secondary to ischemic or idiopathic dilated cardiomyopathy. Of the 712 patients with CHF, 311 had normoalbuminuria, 304 had microalbuminuria, and 97 had macroalbuminuria. The patients with albuminuria had more cardiovascular co-morbidity and worse renal function than those with normoalbuminuria. A total of 152 cardiac events occurred during the follow-up period. Kaplan-Meier analysis demonstrated that patients with albuminuria had a greater incidence of cardiac events than those without albuminuria. Furthermore, albuminuria was significantly associated with an increased risk of cardiac events, even after adjustment for other prognostic variables. In conclusion, albuminuria is a powerful and independent predictor of adverse prognosis in patients with CHF and could be useful for risk stratification of patients with CHF.

Serum pregnancy-associated plasma protein a in patients with heart failure.

BACKGROUND: Pregnancy-associated plasma protein A (PAPP-A) proteolyzes insulin-like growth factor (IGF)-binding proteins and thus increases IGF-1 bioactivity. PAPP-A has been reported to be involved in various pathophysiologic abnormalities; however, the clinical significance of PAPP-A has not been examined in cases of heart failure (HF). We hypothesized that PAPP-A levels might be correlated with the severity of HF. METHODS AND RESULTS: PAPP-A and B-type natriuretic peptide (BNP) levels were measured in 262 subjects (182 HF patients and 80 control subjects). PAPP-A levels were higher in patients with HF than in control subjects and increased with advancing New York Heart Association functional class. There were 53 cardiac events during a mean follow-up period of 796 days. PAPP-A levels were higher in patients with cardiac events than in event-free patients. Patients were divided into 3 groups on the basis of their PAPP-A and BNP levels. Kaplan-Meier analysis demonstrated that the group with both high BNP with high PAPP-A had a significantly higher cardiac event rate than other groups. CONCLUSIONS: Serum PAPP-A levels were related to the severity of HF and associated with a high risk for adverse cardiac events in HF patients, suggesting that PAPP-A might be involved in the pathogenesis of HF.

Differential regulation of diacylglycerol kinase isoform in human failing hearts.

Evidence from several studies indicates the importance of Gαq protein-coupled receptor (GPCR) signaling pathway, which includes diacylglycerol (DAG), and protein kinase C, in the development of heart failure. DAG kinase (DGK) acts as an endogenous regulator of GPCR signaling pathway by catalyzing and regulating DAG. Expressions of DGK isoforms α, ε, and ζ in rodent hearts have been detected; however, the expression and alteration of DGK isoforms in a failing human heart has not yet been examined. In this study, we detected mRNA expressions of DGK isoforms γ, η, ε, and ζ in failing human heart samples obtained from patients undergoing cardiovascular surgery with cardiopulmonary bypass. Furthermore, we investigated modulation of DGK isoform expression in these hearts. We found that expressions of DGKη and DGKζ were increased and decreased, respectively, whereas those of DGKγ and DGKε remained unchanged. This is the first report that describes the differential regulation of DGK isoforms in normal and failing human hearts.

8-Hydroxy-2'-deoxyguanosine is a prognostic mediator for cardiac event.

BACKGROUND: DNA in the nucleus is one of the major targets of reactive oxygen species (ROS), and oxidative DNA damage has been implicated in the pathogenesis of chronic heart failure. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is produced from deoxyguanosine in DNA by ROS. The purpose of this present study was to examine the clinical significance of serum 8-OHdG levels in patients with heart failure. METHODS: We measured serum 8-OHdG levels in 230 patients with chronic heart failure and 42 control subjects without heart failure by sandwich enzyme-linked immunosorbent assay. Patients were prospectively followed during a median follow-up period of 472 days with the end points of cardiac death or progressive heart failure requiring re-hospitalization. RESULTS: Serum 8-OHdG concentrations were higher in patients with heart failure than in control subjects (P < 0·001) and increased with advancing New York Heart Association (NYHA) functional class (P < 0·001). Normal upper limit of 8-OHdG level was determined as mean ± 2SD value from 42 control subjects (0·40 ng mL(-1)). Abnormally high serum 8-OHdG levels (> 0·40 ng mL(-1)) were observed in 21·2%, 43·1%, 42·6% and 69·4% through NYHA I to IV (P < 0·001). A total of 66 cardiac events occurred during a follow-up period, and Kaplan-Meier survival curves demonstrated that cardiac event rate was markedly higher in patients with high 8-OHdG levels than in those with normal 8-OHdG levels (62·4% vs. 29·6%, P = 0·0007). CONCLUSIONS: Serum 8-OHdG levels provide important prognostic information for the risk stratification of patients with heart failure.