The Anti-Inflammatory Effects and Clinical Potential of Dexmedetomidine in Pulmonary Arterial Hypertension.

A pathogenic aspect of pulmonary arterial hypertension (PAH) is the aberrant pulmonary arterial smooth muscle cell (PASMC) proliferation. PASMC proliferation is significantly affected by inflammation. A selective α-2 adrenergic receptor agonist called dexmedetomidine (DEX) modulates specific inflammatory reactions. We investigated the hypothesis that anti-inflammatory characteristics of DEX could lessen PAH that monocrotaline (MCT) causes in rats. In vivo, male Sprague-Dawley rats aged 6 weeks were subcutaneously injected with MCT at a dose of 60 mg/kg. Continuous infusions of DEX (2 µg/kg per hour) were started via osmotic pumps in one group (MCT plus DEX group) at day 14 following MCT injection but not in another group (MCT group). Right ventricular systolic pressure (RVSP), right ventricular end-diastolic pressure (RVEDP), and survival rate significantly improved in the MCT plus DEX group compared with the MCT group [RVSP, 34 mmHg ± 4 mmHg versus 70 mmHg ± 10 mmHg; RVEDP, 2.6 mmHg ± 0.1 mmHg versus 4.3 mmHg ± 0.6 mmHg; survival rate, 42% versus 0% at day 29 (P < 0.01)]. In the histologic study, the MCT plus DEX group showed fewer phosphorylated p65-positive PASMCs and less medial hypertrophy of the pulmonary arterioles. In vitro, DEX dose-dependently inhibited human PASMC proliferation. Furthermore, DEX decreased the expression of interleukin-6 mRNA in human PASMCs treated with fibroblast growth factor 2 (FGF2). These consequences suggest that DEX improves PAH by inhibiting PASMC proliferation through its anti-inflammatory properties. Additionally, DEX may exert anti-inflammatory effects via blocking FGF2-induced nuclear factor κ B activation. SIGNIFICANCE STATEMENT: Dexmedetomidine, a selective α-2 adrenergic receptor agonist utilized as a sedative in the clinical setting, improves pulmonary arterial hypertension (PAH) by inhibiting pulmonary arterial smooth muscle cell proliferation through its anti-inflammatory effect. Dexmedetomidine may be a new PAH therapeutic agent with vascular reverse remodeling effect.

Physical function examination at intensive care unit as predictive indicators for hospitalization-associated disability in patients after cardiovascular surgery.

BACKGROUND: Following cardiovascular surgery, patients are at high risk of requiring systemic management in the intensive care unit (ICU), resulting in hospitalization-associated disability (HAD). Predicting the risk of HAD during the postoperative course is important to prevent susceptibility to cardiovascular events. Assessment of physical function during the ICU stay may be useful as a prediction index but has not been established. METHODS: This prospective observational study conducted at a high-volume cardiovascular center included 236 patients (34% female; median age, 73 years) who required an ICU stay of at least 72 hours after surgery and underwent postoperative rehabilitation. HAD was defined as a decrease in the discharge Barthel index (BI) score of at least 5 points relative to the preadmission BI score. Physical Function ICU Test-scored (PFIT-s), Functional Status Score for the ICU (FSS-ICU), and Medical Research Council (MRC)-sumscore were used to assess physical function at ICU discharge. RESULTS: HAD occurred in 58 (24.6%) of the 236 patients following cardiovascular surgery. The cut-off points for HAD were 7.5 points for the PFIT-s (sensitivity 0.80, specificity 0.59), 24.5 points for the FSS-ICU (sensitivity 0.57, specificity 0.66), and 59.5 points for the MRC-sumscore (sensitivity 0.93, specificity 0.66). Multivariate logistic regression analysis revealed a PFIT-s of >7.5 points (odds ratio [OR], 4.84; 95% CI, 2.39-9.80; p < 0.001) and an MRC-sumscore of >59.5 points (OR, 2.43; 95% CI, 1.22-4.87; p = 0.012) as independent associated factors. CONCLUSIONS: We demonstrate that the PFIT-s and MRC-sumscore at ICU discharge may be helpful as a predictive indicator for HAD in patients having undergone major cardiovascular surgery.

[Asymptomatic Congenital Left Ventricular Aneurysm Treated with Endocardial Linear Infarct Exclusion Technique( ELIET):Report of a Case].

Surgical repair of asymptomatic congenital left ventricular aneurysm is poorly reported. A 30-yearold man presented with an asymptomatic abnormal electrocardiogram. Computed tomography (CT) and angiography revealed a congenital left ventricular aneurysm, and surgical repair was conducted with endocardial linear infarct exclusion technique (ELIET). His postoperative course was uneventful. Postoperative CT showed an elliptical cardiac shape with no recurrence of aneurysm. ELIET would serve as a surgical procedure for congenital left ventricular aneurysm.

[Septal Myectomy for Obstructive Hypertrophic Cardiomyopathy Due to Noonan Syndrome;Report of a Case].

A 15-year-old boy with Noonan syndrome, who had been diagnosed with hypertrophic cardiomyopathy (HCM) at 4 and treated by drugs, was referred to our hospital because of progression of left ventricular outflow tract obstruction (LVOTO). Transthoracic echocardiogram (TTE) revealed left ventricular hypertrophy( LVH), LVOTO( systolic gradient:102 mmHg), and systolic anterior motion of the mitral valve( SAM) with mild mitral regurgitation(MR). We performed septal myectomy by transaortic and transapical approaches. Postoperative TTE revealed significant reduction in left ventricular outflow tract (LVOT) gradient (9 mmHg), resolution of SAM, and reduction in MR grade. The postoperative course was uneventful except for transient atrial tachyarrhythmia. Myectomy for HCM in a patient with Noonan syndrome is rare. This case suggests that myectomy is useful for the patients with Noonan syndrome.

New tailored approach using a revised assessment of fragmented potentials for persistent atrial fibrillation: Early area defragmentation by modified CFAE module.

INTRODUCTION: Pulmonary vein isolation (PVI) is widely performed for atrial fibrillation (AFib). However, it is insufficient to maintain sinus rhythm (SR) in persistent and long persistent atrial fibrillation (Per-AFib). Ablation of complex fractionated atrial electrograms (CFAEs) is currently classified as class IIb, However, the concept of length of potential was different between the current CFAE module of CARTO system and the definition of CFAE potential. The current CFAE module was configured in the shortest complex interval (SCI) mode, in which the meaning of length of potential was the interval of each component of fragmented potentials. That was a part of the potential. On the other hand, the meaning of the definition of CFAE potential was the length of fragmented potential itself. The purpose of this study was to essentially evaluate fragmented potentials by revisiting in interval confidence level (ICL) mode and express them on the map and prospectively investigate the efficacy and prognosis of a new tailored approach for defragmentation, which is called early area defragmentation (EADF). METHODS AND RESULTS: We acquired atrial potentials by modified CFAE module in ICL mode (K-CFAE potential) and visualized the distribution of K-CFAE potential (K-CFAE map). We performed PVI, and we ablated the fragmented areas based on the K-CFAE map. We enrolled 77 patients in this study (control group: 84 patients). After 24-month follow-up, 75.3% were able to maintain SR. CONCLUSIONS: K-CFAE mapping faithfully represented the distribution of fragmented areas. PVI, together with our new tailored approach, EADF, was successful in treating Per-AFib.

Beneficial effects of losartan for prevention of paroxysmal atrial fibrillation in patients with sick sinus syndrome: analysis with memory function of pacemaker.

Renin-angiotensin system (RAS) inhibitors may be useful in preventing the occurrence of paroxysmal atrial fibrillation (PAF). However, evaluation of such effect is difficult because many PAF episodes are asymptomatic and not all episodes are detected by intermittent electrocardiographic monitoring. A pacemaker has been developed with dedicated functions for AF detection and electrocardiogram storage. Accordingly, we examined the effect of losartan, an angiotensin receptor blocker on PAF occurrence using this new modality. We enrolled 70 consecutive patients who had undergone dual-chamber pacemaker implantation for sick sinus syndrome. Finally, 62 patients participated in the study. Thirty patients were randomized to the losartan group (mean 43 ± 12 mg/day) and 32 patients to the control group. They were followed up for 3 months. The frequency, the maximum duration and the total duration of PAF recorded by the stored electrocardiograms for the last 1 month during the observation period and study period were compared between the two groups. The change in the frequency of PAF from the observation period in the losartan and control groups was similar (-35 ± 25 vs. -67 ± 62 times; NS). However, the change in the maximum duration and the total duration of PAF was significantly shorter in the losartan group than in the control group (-493 ± 158 vs. -10 ± 69 min; p < 0.05, and -4007 ± 2334 vs. 1119 ± 714 min; p < 0.05, respectively). Losartan suppressed the maximum duration and the total duration of PAF in patients with sick sinus syndrome without hemodynamic changes. This is the first study to show the effect of a renin-angiotensin system inhibitor on the secondary prevention of PAF using the dedicated functions of a pacemaker for PAF detection and electrocardiogram storage.

Relationships of elevated systemic pentraxin-3 levels with high-risk coronary plaque components and impaired myocardial perfusion after percutaneous coronary intervention in patients with ST-elevation acute myocardial infarction.

BACKGROUND: We aimed to assess the relationships of pentraxin-3 (PTX3) with coronary plaque components and myocardial perfusion after percutaneous coronary intervention (PCI) in order to clarify the mechanisms underlying the prognostic function of PTX3 in ST-elevation acute myocardial infarction (STEMI) patients. METHODS AND RESULTS: We enrolled 75 STEMI patients who underwent pre-PCI virtual histology (VH)-intravascular ultrasound. Relationships of the systemic pre-PCI PTX3 level with coronary plaque components and post-PCI myocardial blush grade (MBG) were evaluated. Lesions with elevated pre-PCI PTX3 (median ≥3.79ng/ml) had higher frequencies of VH-derived thin-cap fibroatheroma (65.8% vs. 24.3%, P<0.0001), plaque rupture (63.2% vs. 24.3%, P=0.001), and post-PCI MBG (0-1) (65.8% vs. 40.5%, P=0.03) than those with PTX3 <3.79ng/ml. In multivariate analysis, pre-PCI PTX3 level was independently related to post-PCI MBG (0-1) (odds ratio, 11.385; 95% confidence interval (CI), 1.346-96.289; P=0.026). At 9-month follow-up, cardiac event-free survival was poorer for patients with post-PCI MBG (0-1) (log-rank test χ(2)=8.6; P=0.003). Cox proportional-hazards analysis showed post-PCI MBG (0-1) (hazard ratio, 4.109; 95% CI, 1.372-12.309; P=0.012) and Killip class >2 on admission (hazard ratio, 5.356; 95% CI, 1.409-20.359; P=0.014) as independent predictors of adverse cardiac events during follow-up. CONCLUSIONS: Systemic pre-PCI PTX3 was associated with high-risk plaque components and impaired post-PCI myocardial perfusion. Thus, PTX3 may be a reliable predictor of outcome in STEMI patients.

Diagnosis and assessment of Takayasu arteritis by multiple biomarkers.

BACKGROUND: Patients with Takayasu arteritis (TA) often show recurrence under steroid treatment without an elevation of C-reactive protein (CRP). There is a report that matrix metalloproteinase (MMP)-2, MMP-3, MMP-9 and pentraxin3 (PTX3) could be sensitive biomarkers, but the characteristics of these biomarkers have not been established. METHODS AND RESULTS: We enrolled 45 consecutive patients; 28 were grouped in an active phase as evidenced by clinical recurrence within 2 years of blood sampling. Circulating levels of high-sensitivity (hs)CRP, MMPs, and PTX3 were determined. Patients in an active phase showed higher levels of hsCRP, MMP-9, and PTX3. Area under the receiving operating characteristics curves of hsCRP and PTX3 were significantly higher than that of MMP-9. Among the 28 patients with active TA, 71% was positive for hsCRP and 82% for PTX3. Patients without recurrence showed significantly higher plasma levels of MMP-9. There was a positive correlation between the plasma MMP-3 level and the prednisolone dose. However, PTX3 and MMP-9 levels did not have such a correlation. CONCLUSIONS: PTX3 and MMP-9, which are not affected by prednisolone, could be sensitive biomarkers for assessing TA activity. Evaluation of MMP-9 may suggest prior existence of TA.

Outcomes of Octogenarians and Nonagenarians in a Contemporary Cardiac Care Unit　- Insights From 2,242 Patients Admitted Between 2019 and 2021.

Background: The number of octo- and nonagenarians admitted to cardiac care units (CCUs) has been increasing in the context of an aging society; however, clinical details and outcomes for these patients are scarce. Methods and Results: Data from 2,242 consecutive patients admitted to the CCU between 2019 and 2021 (age <80 years, 1,390 [62%]; octogenarians, 655 [29%]; nonagenarians, 197 [8.7%]) were reviewed using the in-hospital database for the Tokyo CCU Network. The primary cause of admission was acute coronary syndrome in younger patients and octogenarians (58% and 49%, respectively) and acute heart failure (AHF) in nonagenarians (42%). The proportions of females, underweight, hypertension, atrial fibrillation, myocardial infarction, stroke, previous heart failure, anemia, and malnutrition were higher among octo- and nonagenarians than among younger patients. In-hospital and 1-year mortality rates were greater in octo- and nonagenarians (younger vs. octogenarian vs. nonagenarian, 2.0% vs. 3.8% vs. 5.6% and 4.1% vs. 11.9% vs. 19.0%, respectively). Multivariate analysis revealed that 1-year mortality was associated with octo-/nonagenarian status (odds ratio [OR] 2.24 and 2.64), AHF (OR 2.88), body mass index (OR per 1-kg/m2 0.91), and albumin concentration (OR per 1-g/dL 0.27). Conclusions: Approximately 40% of patients admitted to the CCU were octo- or nonagenarians, and being an octo- or nonagenarian, having AHF, a lower body mass index, and lower albumin concentrations were associated with 1-year mortality after CCU admission.

Progression of hyponatremia is associated with increased cardiac mortality in patients hospitalized for acute decompensated heart failure.

BACKGROUND: Although hyponatremia during hospitalization for acute decompensated heart failure (ADHF) has been reported to correlate with poor prognosis, few studies have examined the effect of progression of hyponatremia on cardiac prognosis in ADHF patients who were normonatremic at admission. METHODS AND RESULTS: Consecutive ADHF patients (n = 662) categorized as New York Heart Association Class III or IV were investigated retrospectively. Of these patients, 634 who survived to discharge were examined and 531 were normonatremic (serum sodium concentration [Na] ≥ 135 and ≤ 145 mmol/L) at admission. The 531 patients were divided into 2 groups: the non-developed group, who remained normonatremic at discharge (n = 455), and the developed group, who had progressed to hyponatremia (Na < 135 mmol/L) at discharge (n = 76). The cardiac event-free rate after 12 months was significantly lower in the developed group than in the non-developed group (22% vs. 71%; P < .0001). Although their baseline levels of brain natriuretic peptide and left ventricular ejection fraction were similar before discharge, the patients in the developed group exhibited higher fractional excretion of sodium and received higher doses of diuretics than did those in the non-developed group. CONCLUSION: Our data suggest that progression to hyponatremia during hospitalization is a robust predictor of poor cardiac prognosis in ADHF patients who were normonatremic at admission.

Improved prognosis of Takayasu arteritis over the past decade--comprehensive analysis of 106 patients.

BACKGROUND: We aimed to describe the recent clinical characteristics of Takayasu arteritis (TA). METHODS AND RESULTS: We enrolled 106 consecutive TA patients and compared the clinical characteristics of patients with TA onset before 1999 and after 2000, patients with onset at age less than 39 years and more than 40 years, patients with monophasic and relapsing-remitting clinical course, and patients with and without human lymphocyte antigen (HLA)-B52 allele. Among the patients with TA onset after 2000, the time from onset to diagnosis had decreased; the frequency of occlusion in aortic arch branches and the complication of moderate or severe aortic regurgitation (AR) had decreased, and the maximum dose of prednisolone and the use of immunosuppressive agents had increased. In patients with onset at age more than 40 years, the complications of coronary artery lesions and hypertension had increased, and the incidence of moderate or severe AR had decreased. In the relapsing-remitting group, the maximum dose of prednisolone and the use of immunosuppressive agents had increased, and the mean dose reduction rate of prednisolone was significantly high. There was no significant difference between patients with and without HLA-B52 allele. CONCLUSIONS: The prognosis of TA patients has improved over the past decade, which may be related to early diagnosis because of the development of noninvasive diagnostic imaging tools and improved medical treatments.

How to avoid development of AV block during RF ablation: anatomical and electrophysiological analyses at the time of AV node ablation.

BACKGROUND: With an aim to identify risk factors that can serve for prevention of atrioventricular (AV) block (AVB) during radiofrequency (RF) ablation, we conducted anatomical and electrophysiological investigations at the time of AV node ablation (AVNA). METHODS AND RESULTS: Ten patients who underwent AVNA were enrolled. RF energy was delivered from posterior region of septal annulus of the tricuspid valve to the His bundle potential (HBP) recording site using a stepwise approach. In each delivery, atrial/ventricle potential amplitude ratio (A/V ratio), HBP, and juctional ectopy (JE) that appeared during RF delivery were evaluated. Furthermore, fluoroscopic distance between ablation site and HBP recording site (anatomical H-ABL distance) and electrophysiological H-ABL interval were measured. HBP was recorded in 25 of total 70 RF deliveries. When HBP was recorded, the A/V ratio was significantly greater in the group with AVB than without AVB (1.6 ± 2.3 mV vs 0.1 ± 0.2 mV, P = 0.02). The minimum cycle length (CL) of JE was significantly shorter in the group with AVB than without AVB (438 ± 112 ms vs 557 ± 178, ms, P = 0.04). AVB developed frequently when H-ABL distance was less than 15 mm from right anterior oblique view 30° and 12 mm from left anterior oblique view 45° and when H-ABL interval was less than 10 ms. AVB did not develop over the above values. CONCLUSIONS: HBP with high A/V ratio, JE with short CL, short H-ABL distance, and short H-ABL interval of less than 10 ms should be avoided to prevent AVB during RF ablation at the near site of AV node.

Development and implementation of an advanced coronary angiography and intervention database system.

The 'evidence' in evidence-based medicine (EBM) is often limited to knowledge obtained from randomized controlled clinical trials (RCT). Most RCTs, however, have strict enrollment criteria which make patient background characteristics and clinical histories significantly different from those encountered in actual practice. Thus it is important to accumulate and analyze data obtained in daily practice to gain insight into a larger clinical picture. Recent developments in information technology and its lowered cost have enabled us to record clinical activity in much greater detail at a lower cost. These factors prompted us to design and develop a coronary angiography and intervention reporting system (CAIRS) to collect data and analyze outcomes of coronary intervention. The resulting advanced CAIRS can record detailed data on coronary angiographic and interventional procedures.To date, data on 10,025 cases of coronary angiography, of which 3,574 were interventional, have been collected over a 5.5 year period. There were 4,343 unique patients, 3,115 (71.7%) of which were male. The overall mean age was 67.0 ± 11.5. The mean age of males was 66.3 ± 11.4 and that of females was 69.0 ± 11.4. About one-third of the patients never underwent a PCI procedure at our institution. For patients that underwent at least one PCI procedure at our institution, the prescription rate of statin increased from 50.8% in 2005 to 80.3% in 2011, while those of nitrate and ticlopidine decreased from 36.7% and 90.8% in 2005 to 21.3% and 0.8% in 2011, respectively. We have also implemented the same system at another institution and compared the data on stent usage between the two institutions, which revealed vastly different stent usage profiles.In conclusion, we have successfully developed and implemented an advanced coronary angiography and intervention reporting system which we call CAIRS. Implementing the same system at multiple institutions and analyzing data collected from several institutions will provide detailed and timely insight into the 'real world' of coronary angiography and interventional procedures and their outcome.

Coronary ostial angioplasty for juvenile Takayasu arteritis involving the coronary artery using external iliac artery grafts.

Takayasu arteritis can affect the coronary ostia, leading to myocardial ischemia. Coronary ostial angioplasty effectively treats coronary artery ostial lesions associated with Takayasu arteritis. We present a case of juvenile Takayasu arteritis with bilateral subclavian artery occlusions treated with a novel coronary artery ostial angioplasty using the external iliac artery.

Factors Related to Hospitalisation-Associated Disability in Patients after Surgery for Acute Type A Aortic Dissection: A Retrospective Study.

The in-hospital mortality rate among patients after surgery for acute type A aortic dissection (ATAAD) has improved chronologically. However, the relationship between the incidence of hospitalisation-associated disability (HAD) and acute cardiac rehabilitation in patients after surgery for ATAAD has not been reported. Therefore, this study evaluated factors related to HAD in patients after surgery for ATAAD. This single-centre retrospective observational study included 483 patients who required emergency surgery for ATAAD. HAD occurred in 104 (21.5%) patients following cardiovascular surgery. Factors associated with HAD were age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.02-1.09; p = 0.001), noninvasive positive pressure ventilation (NPPV; OR, 2.15; 95% CI, 1.10-4.19; p = 0.025), postoperative delirium (OR, 2.93; 95% CI, 1.60-5.37; p = 0.001), and timing of walking onset (OR, 1.29; 95% CI, 1.07-1.56; p = 0.008). Furthermore, a late walking onset was associated with a higher risk of developing HAD and more severe functional decline. Early rehabilitation based on appropriate criteria has possibility of preventing HAD.

Telmisartan, a unique ARB, improves left ventricular remodeling of infarcted heart by activating PPAR gamma.

Unfavorable left ventricular (LV) remodeling after myocardial infarction (MI) leads to cardiac dysfunction. We examined whether Telmisartan, an angiotensin (Ang) II type I receptor blocker (ARB), could improve the recovery of LV function in a rat model of MI. The effect of Telmisartan as a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist was also investigated. After 28 days of MI, a significant improvement of survival was observed in the Telmisartan-treated rat group compared with the vehicle control rat group, non-PPAR-γ agonistic ARB (Losartan)-treated rat group, and Telmisartan plus specific PPAR-γ antagonist (GW9662)-treated rat group. Although no significant differences of blood pressure or infarct size were observed among these four groups, the Telmisartan group had better systolic and diastolic LV function. There was a significant reduction of the plasma brain natriuretic peptide level, cardiac fibrosis area, infiltration of macrophages, size of cardiomyocytes, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive myocytes, activation of matrix metalloproteinases-2 and -9 (MMPs-2/9), and expression of transforming growth factor ß-1 (TGF-ß1), connective tissue growth factor (CTGF), and osteopontin (OPN), while expression of PPAR-γ and activation of tissue inhibitor of metalloproteinase-1 (TIMP-1) was enhanced, in the noninfarcted myocardium of rats from the Telmisartan group compared with the other three groups. To mimic ischemic conditions in vitro, neonatal rat cardiomyocytes and cardiac fibroblasts were incubated in hypoxic condition for 24 h. Increased transcriptional activation of PPAR-γ and TIMP-1, and inhibition of TGF-ß1 expression were observed in cardiomyocytes, while decreased activation of MMPs-2/9 and decrease in CTGF and OPN expression was seen in cardiac fibroblasts cultured with Telmisartan. In conclusion, Telmisartan prevented unfavorable cardiac remodeling through a reduction of cardiac hypertrophy and fibrosis. An anti-inflammatory effect and PPAR-γ activation were suggested to be important in addition to suppression of Ang II activity.

Additive effects of ß-blockers on renin-angiotensin system inhibitors for patients after acute myocardial infarction treated with primary coronary revascularization.

BACKGROUND: Although some ß-blockers are effective for patients after acute myocardial infarction (AMI), few studies have compared their additive effects on renin-angiotensin system inhibitors (RAS-Is). METHODS AND RESULTS: The 251 consecutive AMI patients administered angiotensin-converting-enzyme inhibitors (ACE-Is) or angiotensin-II receptor blockers (ARBs) were retrospectively investigated and divided into 2 groups: treated without ß-blockers (no-ß-blocker group, n=80) or treated with ß-blockers before discharge (ß-blocker group, n=171; carvedilol [n=91] or bisoprolol [n=80]). The doses of RAS-Is used for patients in the no-ß-blocker group were at least double those used in the ß-blocker group. No significant differences between the 2 groups were observed with regard to baseline characteristics. After a 12-month follow-up, the survival and cardiac event-free rates in the ß-blocker group were significantly higher than those in the no-ß-blocker group. The percent change in blood pressure did not significantly differ between the 2 groups, but the levels of brain natriuretic peptide, metalloproteinase-2, and metalloproteinase-9 and the left ventricular ejection fraction improved significantly in the ß-blocker group compared with the no-ß-blocker group. Regarding the 2 ß-blockers, carvedilol treatment produced more favorable outcomes than bisoprolol. CONCLUSIONS: The data suggest that treatment with RAS-I in combination with ß-blocker is more effective for patients after AMI than treatment with RAS-I alone.

Effect of adiponectin on cardiac allograft vasculopathy.

BACKGROUND: The role of adiponectin (APN), an adipose tissue-specific secretory protein, on chronic rejection after cardiac transplantation in APN-sense transgenic mice (APN-SE) was evaluated. METHODS AND RESULTS: Heterotopic cardiac transplantation in major histocompatibility complex class II-mismatched mice was performed. B6.C-H-2(bm12)KhEg (Bm12) hearts were transplanted into APN-SE, and allografts were harvested at 8 weeks after transplantation. Quantitative polymerase chain reaction (PCR) and immunohistochemical staining showed that the expression of both AdipoR1 and AdipoR2 was induced in APN-SE recipients. Neointimal hyperplasia was significantly decreased in allografts transplanted into APN-SE (luminal occlusion, 8.9 ± 2.2%) compared to those transplanted into controls (49.4 ± 10.5%; P=0.011). APN-SE showed significantly reduced mRNA levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-6, and monocyte chemoattractant protein-1 (MCP-1) by quantitative PCR. Western blot analysis revealed that the protein levels of IFN-γ and MCP-1 were reduced in APN-SE recipients. Proliferation of smooth muscle cells stimulated with activated T cells was suppressed by APN addition, and this effect was canceled by treatment with an adenosine monophosphate-activated protein kinase (AMPK) inhibitor. CONCLUSIONS: APN plays a critical role in the attenuation of chronic rejection by suppressing inflammatory cytokine and chemokine expression and enhancing APN receptor expression. APN plays a beneficial role in reducing the progression of cardiac allograft vasculopathy through the AMPK pathway.

Cardiovascular and renal effects of carperitide and nesiritide in cardiovascular surgery patients: a systematic review and meta-analysis.

INTRODUCTION: Acute kidney injury (AKI) following cardiovascular surgery is a common disease process and is associated with both morbidity and mortality. The aim of our study was to evaluate the cardiovascular and renal effects of an atrial natriuretic peptide (ANP, carperitide) and a B-type (or brain) natriuretic peptide (BNP, nesiritide) for preventing and treating AKI in cardiovascular surgery patients. METHODS: Electronic databases, including PubMed, EMBASE and references from identified articles were used for a literature search. RESULTS: Data on the infusion of ANP or BNP in cardiovascular surgery patients was collected from fifteen randomized controlled trials and combined. The infusion of ANP or BNP increased the urine output and creatinine clearance or glomerular filtration rate, and reduced the use of diuretics and the serum creatinine levels. A meta-analysis showed that ANP infusion significantly decreased peak serum creatinine levels, incidence of arrhythmia and renal replacement therapy. The meta-analysis also showed that ANP or BNP infusion significantly decreased the length of ICU stay and hospital stay compared with controls. However, the combined data were insufficient to determine how ANP or BNP infusion during the perioperative period influences long-term outcome in cardiovascular surgery patients. CONCLUSIONS: The infusion of ANP or BNP may preserve postoperative renal function in cardiovascular surgery patients. A large, multicenter, prospective, randomized controlled trial will have to be performed to assess the therapeutic potential of ANP or BNP in preventing and treating AKI in the cardiovascular surgical setting.

Comparative effects of carvedilol vs bisoprolol for severe congestive heart failure.

BACKGROUND: Although carvedilol and bisoprolol are effective medicines for the treatment of patients with heart failure (HF), only a few reports have compared their effects. This study was designed to compare the effects of them in patients with severe HF. METHODS AND RESULTS: A total of 655 consecutive patients with HF, categorized as New York Heart Association Class 3 or 4, were retrospectively investigated. Of these patients, 217 were administered beta-blockers after admission and were divided into 2 groups (carvedilol, n=110; bisoprolol, n=107). No significant differences were observed in their characteristics between the 2 groups prior to the introduction of the beta-blockers. After 18 months of follow-up, there were no significant differences in the survival and cardiac event-free rates between the 2 groups. In contrast, there were several significant differences in patients with atrial fibrillation (AF) (carvedilol, n=40; bisoprolol, n=43). The percent changes in heart rate and brain natriuretic peptide level improved significantly in the bisoprolol group than in the carvedilol group. Furthermore, more patients in the bisoprolol group were defibrillated from AF to sinus rhythm than those in the carvedilol group (48% vs 16%; P=0.03). CONCLUSIONS: Our data suggest that the 2 beta-blockers are equally effective in the improvement of severe HF, but bisoprolol shows favorable effects in patients with AF.