Gender Difference in the Prognostic Value of N-Terminal Pro-B Type Natriuretic Peptide in Patients With Heart Failure　- A Report From the Korean Heart Failure Registry (KorHF).

BACKGROUND: Very little data is available to evaluate the gender-specific role of N-terminal pro-B type natriuretic peptide (NT-proBNP). This study was performed to investigate whether there is a gender difference in the prognostic value of NT-proBNP in patients hospitalized for heart failure (HF).Methods and Results:A total of 2,280 patients hospitalized with HF (67.9±14.3 years, 50.9% women) from the nationwide registry database were analyzed. Composite events including all-cause mortality and HF readmission were assessed. During the mean follow-up period of 1,245±824 days, there were 1,067 cases of composite events (49.7%). NT-proBNP levels were significantly higher in patients with events than those without in both genders (P<0.001 for each). A higher NT-proBNP level was an independent predictor of events (highest vs. lowest tertile: hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.25-2.43; P=0.001) in men, even after controlling for potential confounders. However, NT-proBNP was not associated with the occurrence of composite events in women in the same multivariable analysis (P>0.05). CONCLUSIONS: In patients with HF, the NT-proBNP level seems to be a more valuable marker in the prediction of long-term mortality and HF readmission in men than in women.

High sodium intake in women with metabolic syndrome.

BACKGROUND AND OBJECTIVES: Metabolic syndrome and high sodium intake are associated with frequent cardiovascular events. Few studies have estimated sodium intake in subjects with metabolic syndrome by 24-hour urine sodium excretion. We evaluated sodium intake in individuals with metabolic syndrome. SUBJECTS AND METHODS: Participants were recruited by random selection and through advertisement. Twenty four-hour urine collection, ambulatory blood pressure measurements, and blood test were performed. Sodium intake was estimated by 24-hour urine sodium excretion. Participants receiving antihypertensive medications were excluded from analysis. RESULTS: Among the 463 participants recruited, subjects with metabolic syndrome had higher levels of 24-hour urine sodium excretion than subjects without metabolic syndrome (p=0.0001). There was a significant relationship between the number of metabolic syndrome factors and 24-hour urine sodium excretion (p=0.001). The proportion of subjects with metabolic syndrome was increased across the tertile groups of 24-hour urine sodium excretion (p<0.0001). The association of high sodium intake and metabolic syndrome was significant only among women. Among the factors related to metabolic syndrome, body mass index had an independent association with 24-hour urine sodium excretion (p<0.0001). CONCLUSION: Women with metabolic syndrome exhibited significantly higher sodium intake, suggesting that dietary education to reduce sodium consumption should be emphasized for women with metabolic syndrome.

Brachial-ankle pulse wave velocity for the prediction of the presence and severity of coronary artery disease.

The predictability of brachial-ankle pulse wave velocity (baPWV) for the presence and severity of coronary artery disease (CAD) was investigated by measuring baPWV in 501 subjects scheduled for coronary angiography. Severity of CAD was measured using modified Gensini stenosis score (GSS) and classified as a vessel disease score (VDS) of 0-3. The presence of CAD was defined as diameter stenosis>50%. Subjects were grouped in tertile by level of baPWV (<14, 14-17, >17 m/s). Subjects with CAD showed higher mean age, prevalence of men and diabetes, and systolic blood pressure. The prevalence of hypertension, use of antihypertensive medications and use of statin was not different. Subjects with CAD had higher baPWV than subjects without CAD (16.70 ± 3.46 versus 15.21 ± 3.19 m/s, p<0.001). Multiple linear regression analysis showed significant correlation of baPWV and modified GSS (p=0.0337). ANCOVA adjusted with age, gender, body mass index, presence of hypertension or diabetes, status of smoking, use of antihypertensive medications and risk of hypercholesterolemia showed a statistically significant association of baPWV with VDS (p<0.0001). Highest tertile of baPWV had a statistically significant effect on the severity of CAD from an ANCOVA model. The predictive power of highest tertile of baPWV for the presence of CAD was 3.600 [95% confidence interval (CI) 1.884-6.881, p<0.0001]. It is concluded that increased baPWV is a reliable predictor of the presence and severity of CAD, suggesting that baPWV>17 m/s may be a threshold value for the presence and severity of CAD.

Subclinical renal insufficiency range of estimated glomerular filtration rate and microalbuminuria are independently associated with increased arterial stiffness in never treated hypertensives.

BACKGROUND AND OBJECTIVES: Microalbuminuria (MAU) and decreased estimated glomerular filtration rate (eGFR) are risk factors for cardiovascular disease (CVD) in patients with hypertension. However, in hypertensive patients with normal or minimally reduced eGFR (≥60 mL/min/1.73 m(2)) and with normo- or MAU, the value of combined estimation of eGFR and urine microalbumin for the risk assessment has not been widely reported. We evaluated the association between arterial stiffness and the combined estimation of eGFR and urine microalbumin. SUBJECTS AND METHODS: Subjects with never treated hypertension and normal or minimally reduced eGFR were evaluated (n=491, 50.1±10.4 years). eGFR was calculated by the simplified Modification of Diet in Renal Disease formula. Urinary albumin-to-creatinine ratio (UACR) was assessed with spot urine. Arterial stiffness was assessed with heart-femoral pulse wave velocity (hfPWV). All subjects were divided into four groups; group 1, eGFR ≥90 mL/min/1.73 m(2) (normal eGFR) and normo-albuminuria (NAU); group 2, eGFR 89.9-60 mL/min/1.73 m(2) (minimally reduced eGFR) and NAU; group 3, normal eGFR and MAU; group 4, minimally reduced eGFR and MAU. RESULTS: Group 1 had the lowest hfPWV (964.6±145.4; group 2, 1013.5±168.9; group 3, 1058.2±238.0; group 4, 1065.8±162.9 cm/sec). Analysis adjusting age, sex, body mass index, heart rate and mean arterial pressure showed significantly lower hfPWV of group 1 compared to group 2 (p=0.032) and 3 (p=0.007). Multiple regression analysis showed a significant association of hfPWV with logUACR {beta=0.096, 95% confidence interval (CI) 8.974-60.610, p=0.008} and eGFR (beta=-0.069, 95% CI -1.194 - -0.005, p=0.048). CONCLUSION: Minimally reduced eGFR or MAU is independently associated with increased arterial stiffness, indicating greater CVD risk.

Exercise attenuates matrix metalloproteinase activity in preexisting atherosclerotic plaque.

OBJECTIVE: Few studies have investigated if exercise by itself has anti-atherosclerotic effects, without combining interventions with a low-fat diet. We studied the effects of exercise as a stand-alone intervention on preexisting atheromata by measuring not only plaque size but also the levels of plaque-destabilizing matrix-metalloproteinase (MMP) activity in vivo. METHODS AND RESULTS: We used near-infrared fluorescent (NIRF) molecular imaging with an MMP-2/9 activatable NIRF probe to visualize the inflammatory protease activity within preexisting atheromata of 17-week-old ApoE(-/-) mice on: (a) normal chow diet (NCD), (b) Western diet (WD), and (c) WD with treadmill exercise for 10 weeks. We also measured tissue levels of aortic lipid peroxidation (LPO) and plasma levels of glucose/lipid/cytokine profiles. Exercise did not attenuate growth of preexisting atheromatous plaques. However, exercise strongly decreased proteolytic activity in plaques for animals on WD, with levels decreasing almost to NCD levels. Exercise was associated with decreased aortic LPO levels and increased blood adiponectin/leptin levels; however, exercise did not affect WD-consumption/weight-gain or improve blood glucose/lipid profiles. CONCLUSIONS: Exercise training reduced aortic MMP activity in mice with preexisting atheromata, even though they remained on a high fat diet and plaque-growth was not attenuated.

Effect of Korean red ginseng on arterial stiffness in subjects with hypertension.

OBJECTIVES: Korean red ginseng (KRG) improves endothelial function and lower blood pressure (BP), which may affect arterial stiffness. The present study evaluated whether KRG treatment could improve arterial stiffness in subjects with hypertension. SUBJECTS AND METHODS: Eighty (80) participants with hypertension who were treated with antihypertensive agents were randomly assigned to an active (KRG 3 g/day) or a placebo treatment group in a double-blind manner. Participants were not allowed to change their antihypertensive medications. Systolic BP (SBP) and diastolic BP (DBP) were measured at baseline, and at 1, 2, and 3 months. Arterial stiffness was assessed by the measurement of brachial-ankle pulse wave velocity (baPWV) at baseline, and at 1 and 3 months. RESULTS: Thirty (30) subjects in the active group (AG) and 34 subjects in the placebo group (PG) completed 3 months of treatment and then a per-protocol analysis was done. SBP and DBP at baseline, and at 1, 2, and 3 months were not different between the AG and PG (p>0.05). After 3 months of treatment, SBP of AG was not changed from SBP at baseline. However, DBP of AG, and SBP and DBP of PG after 3 months of treatment were significantly reduced (p<0.05). baPWV of both groups was significantly reduced at 1 and 3 months (p<0.05), but was not different between the groups at each time point. Analysis after adjustment for age, time-dependent mean arterial BP, heart rate, and levels of fasting blood glucose and triglycerides showed no significant difference between AG and PG in changes of baPWV from baseline to 1 and 3 months (p>0.05). CONCLUSIONS: Three (3) months' treatment with KRG did not improve arterial stiffness in subjects with hypertension.

Relationship between serum uric Acid levels, metabolic syndrome, and arterial stiffness in korean.

BACKGROUND AND OBJECTIVES: Associations have been reported between the serum uric acid (SUA) level, metabolic syndrome (MS), and atherosclerosis. We have determined the relationship between the SUA level, MS, and arterial stiffness in Korean. SUBJECTS AND METHODS: Cross-sectional data from 1,276 adults who underwent routine laboratory tests and pulse wave velocity (PWV) measurements during a health check-up were analyzed in a gender-specific manner. None of the participants had atherosclerotic cardiovascular disease, diabetes, renal disease, or systemic disease, or were under treatment which would affect SUA levels, or taking medications for hypertension or dyslipidemia. RESULTS: After adjustment for age, smoking status, total cholesterol (TC), and creatinine, the odds ratios (ORs, 95% confidence interval) of gender-specific quartiles of SUA for MS were 1.0, 1.28 (0.66-2.47), 1.46 (0.76-2.82), and 2.21 (1.15-4.26) in females, and 1.0, 1.33 (0.82-2.17), 1.60 (0.96-2.66), and 2.03 (1.21-3.40) in males. However, after adjustment for waist circumference, there were no significant differences in the ORs among the SUA quartile groups in females and males (both, p=NS). The Pearson's correlation coefficients for the relationship between SUA levels and heart-femoral (hf) PWVs or brachial-ankle (ba) PWVs were not significant in females and males (r=0.054 and r=0.015, respectively, in females; r=-0.036 and r=-0.015, respectively, in males; all, p=NS). CONCLUSION: An elevated SUA level is associated with abdominal obesity among the MS components, but the SUA level is not associated with PWV in females or males.

Protease imaging of human atheromata captures molecular information of atherosclerosis, complementing anatomic imaging.

OBJECTIVE: There is hope that molecular imaging can identify vulnerable atherosclerotic plaques. However, there is a paucity of clinical translational data to guide the future development of this field. Here, we cross-correlate cathepsin-B or matrix metalloproteinase-2/-9 molecular optical imaging data of human atheromata or emboli with conventional imaging data, clinical data, and histopathologic data. METHODS AND RESULTS: Fifty-two patients undergoing carotid endarterectomy (41 atheromata) or carotid stenting (15 captured emboli) were studied with protease-activatable imaging probes. We show that protease-related fluorescent signal in carotid atheromata or in emboli closely reflects the pathophysiologic alterations of plaque inflammation and statin-mediated therapeutic effects on plaque inflammation. Inflammation-related fluorescent signal was observed in the carotid bifurcation area and around ulcero-hemorrhagic lesions. Pathologically proven unstable plaques had high cathepsin-B-related fluorescent signal. The distribution patterns of the mean cathepsin-B imaging signals showed a difference between the symptomatic vs asymptomatic plaque groups. However, the degree of carotid stenosis or ultrasonographic echodensity was weakly correlated with the inflammatory proteolytic enzyme-related signal, suggesting that molecular imaging yields complimentary new information not available to conventional imaging. CONCLUSIONS: These results could justify and facilitate clinical trials to evaluate the use of protease-sensing molecular optical imaging in human atherosclerosis patients.

Treatment of diffuse in-stent restenosis with drug-eluting stents vs. intracoronary beta-radiation therapy: INDEED Study.

BACKGROUND: We compared sirolimus-eluting stent (SES) implantation and intracoronary brachytherapy (ICBT) for diffuse bare metal in-stent restenosis (ISR) to identify more effective treatment modality. METHODS: Patients (n=129) with diffuse ISR (lesion length > or = 10 mm) were randomly assigned to either SES implantation (n=65, group I) or beta-radiation with 188Re-MAG(3)-filled balloon (n=64, group II). The radiation dose was 20 Gy at a depth of 1.0 mm into the vessel wall. The primary end point was late loss in analysis segment at 6 months. The secondary end points were 6-month angiographic restenosis and 1-year major adverse cardiac events (MACE) including myocardial infarction (MI), cardiac death, and target lesion revascularization (TLR). RESULTS: Baseline characteristics were similar between two groups. The lesion length was 27.52+/-13.98 mm in group I and 27.75+/-14.25 mm in group II (p=0.927). Late loss in analysis segment at 6 months was smaller in group I than in group II (0.15+/-0.62 vs. 0.55+/-0.69 mm, p=0.003). Angiographic restenosis for analysis segment at 6 months was 8.0% (4/50) in group I and 30.2% (16/53) in group II (p=0.006). One MI and two deaths (all from group I) occurred during follow-up. TLR (4.6% vs. 18.8%, p=0.014) and MACEs (7.7% vs. 18.8%, p=0.073) were lower in group I than group II at 1 year. CONCLUSION: Compared to ICBT, SES implantation for diffuse bare metal ISR showed less late loss, lower restenosis, and a trend toward lower 1-year MACEs. SES implantation appears to be superior to ICBT for treating diffuse ISR.

Acute effects of cigarette smoking on arterial stiffness and blood pressure in male smokers with hypertension.

BACKGROUND: Although the acute increase of arterial stiffness and blood pressure (BP) after cigarette smoking in healthy smokers is considered a possible mechanism of increased cardiovascular risk, the acute effect of smoking on arterial stiffness in hypertensive smokers is unknown. We investigated the acute effects of cigarette smoking on arterial stiffness and BP in hypertensive male smokers. METHODS: Heart rate (HR), brachial and ankle BP, and pulse-wave velocity (PWV) were measured in 22 hypertensive male smokers (HTs) and in 30 normotensive male smokers (NTs) before and 5, 10, and 15 min after smoking one cigarette (nicotine content, 0.9 mg). RESULTS: Smoking induced acute increases of HR, brachial BP, and heart-femoral PWV (hfPWV) in NTs and HTs (P < .05). Ankle systolic BP and femoral-ankle PWV were acutely increased in HTs (P < .05), but not in NTs. In HTs, brachial systolic BP and hfPWV at 15 min were higher than at baseline (P < .05). An acute increase of hfPWV in the HTs was significant (P = .025) after adjustment for total cholesterol, time-dependent HR, and brachial mean arterial pressure, but acute changes of other PWVs lost statistical significance. CONCLUSIONS: Cigarette smoking acutely increases aortic stiffness and BP in male smokers with hypertension, and the effects persist longer than in male smokers without hypertension.

Renal toxicity evaluation and comparison between visipaque (iodixanol) and hexabrix (ioxaglate) in patients with renal insufficiency undergoing coronary angiography: the RECOVER study: a randomized controlled trial.

OBJECTIVES: This study sought to compare the nephrotoxicity of iodixanol and ioxaglate in patients with renal impairment undergoing coronary angiography. BACKGROUND: Iodixanol, a nonionic, dimeric, iso-osmolar contrast medium (IOCM), may be less nephrotoxic than low-osmolar contrast media (LOCM) in high-risk patients. METHODS: In a prospective, randomized trial in 300 adults with creatinine clearance (CrCl) < or =60 ml/min, patients received either iodixanol or ioxaglate and underwent coronary angiography with or without percutaneous coronary intervention. The primary end point was the incidence of contrast-induced nephropathy (CIN) (an increase in serum creatinine [SCr] > or =25% or > or =0.5 mg/dl [> or =44.2 mumol/l]). The incidence of CIN in patients with severe renal impairment at baseline (CrCl <30 ml/min) or diabetes and in those receiving large doses (> or =140 ml) of contrast medium was also determined. RESULTS: The incidence of CIN was significantly lower with iodixanol (7.9%) than with ioxaglate (17.0%; p = 0.021), corresponding to an odds ratio (OR) of CIN of 0.415 (95% confidence interval [CI] 0.194 to 0.889) for iodixanol. The incidence of CIN was also significantly lower with iodixanol in patients with severe renal impairment (p = 0.023) or concomitant diabetes (p = 0.041), or in patients given > or =140 ml of contrast media (p = 0.038). Multivariate analysis identified use of ioxaglate (OR 2.65, 95% CI 1.11 to 6.33, p = 0.028), baseline SCr, mg/dl (OR 2.0, 95% CI 1.04 to 3.85, p = 0.038), and left ventricular ejection fraction, % (OR 0.97, 95% CI 0.94 to 0.99, p = 0.019) as independent risk factors for CIN. CONCLUSIONS: The IOCM iodixanol was significantly less nephrotoxic than ioxaglate, an ionic, dimeric LOCM. (The RECOVER Trial; http://clinicaltrials.gov; NCT00247325).

Increased risk of atherothrombotic events associated with cytochrome P450 3A5 polymorphism in patients taking clopidogrel.

BACKGROUND: Clopidogrel is a prodrug requiring metabolism by cytochrome P450 3A (CYP3A) isoenzymes, including CYP3A5, in order to be active. It is controversial whether clopidogrel interacts with CYP3A inhibitors. We investigated the influence of CYP3A5 polymorphism on the drug interaction of clopidogrel. METHODS: In phase 1 of the study, we administered clopidogrel to 16 healthy volunteers who had the CYP3A5 non-expressor genotype (*3 allele) and 16 who had the CYP3A5 expressor genotype (*1 allele) with and without pretreatment with itraconazole, a potent CYP3A inhibitor. A platelet aggregation test was performed at baseline, 4 hours, 24 hours and 6 days after clopidogrel administration. In phase 2, we compared clinical outcomes of 348 patients treated with clopidogrel after successful coronary angioplasty with bare-metal stent implantation according to their CYP3A5 genotype; the primary end point was a composite of atherothrombotic events (cardiovascular death, myocardial infarction and non-hemorrhagic stroke) within 1 and 6 months after stent implantation. RESULTS: In phase 1, the change in platelet aggregation after clopidogrel administration and pretreatment with itraconazole was greater among the subjects with the CYP3A5 expressor genotype than among those with the non-expressor genotype: 24.9% (standard deviation [SD] 13.9%) v. 6.2% (SD 13.5%) at 4 hours (p < 0.001); 27.7% (SD 16.5%) v. 2.5% (SD 8.3%) at 24 hours (p < 0.001); and 33.5% (SD 18.6%) v. 17.8% (SD 13.8%) at day 7 (p < 0.01). In phase 2, atherothrombotic events occurred more frequently within 6 months after stent implantation among the patients with the non-expressor genotype than among those with the expressor genotype (14/193 v. 3/155; p = 0.023). Multivariable analysis showed that the CYP3A5 polymorphism was a predictor of atherothrombotic events in clopidogrel users. INTERPRETATION: People with the CYP3A5 non-expressor genotype are vulnerable to drug interactions between clopidogrel and CYP3A inhibitors. This phenomenon may be associated with worse outcomes in patients with the non-expressor genotype who are given clopidogrel after coronary angioplasty and implantation of bare-metal stents.

One month follow-up C-reactive protein may be a useful predictor of angiographic restenosis and long-term clinical outcomes after bare metal stent implantation.

We report C-reactive protein (CRP) measured 1 month after stenting was an independent predictor of angiographic restenosis, and patients with both elevated preprocedural CRP and CRP 1 month after stenting had the worst long-term clinical outcomes. Measurement of CRP during follow-up in addition to preprocedural CRP may improve risk stratification after coronary stenting.

Comparison of sirolimus-eluting stent, paclitaxel-eluting stent, and bare metal stent in the treatment of long coronary lesions.

OBJECTIVE: This study compared the efficacy of the sirolimus-eluting stent (SES), the paclitaxel-eluting stent (PES), and the bare metal stent (BMS) for long coronary lesions. BACKGROUND: The outcome of drug-eluting stent (DES) implantation in long coronary lesions remains unclear. METHODS: The study involved 527 patients with de novo long coronary lesions (> or = 24 mm), which were treated with long (> or = 28 mm) SESs (223 lesions), PESs (194 lesions), or BMSs (201 lesions). RESULTS: Lesions in the SES (36.0 +/- 14.9 mm, P < 0.001) and PES (36.3 +/- 14.5 mm, P < 0.001) groups were longer than those in the BMS group (32.0 +/- 12.3 mm), meaning the two DES groups had longer stented segments than did the BMS group. Six-month angiographic follow-up showed the SES (9.3%, P < 0.001) and PES (21.3%, P < 0.001) groups had lower in-segment restenosis rates than that of the BMS group (42.5%). The rate of major adverse cardiac events (MACE) including death, myocardial infarction, and target lesion revascularization at 9 months was higher in the BMS group (26.6%) than that in the SES (13.0%, P < 0.001) and PES (15.7%, P < 0.001) groups. Posthoc analysis of the two DES groups showed that the in-segment restenosis rate was lower for the SES than that for the PES group (P = 0.002), while the MACE rate was similar. CONCLUSIONS: The use of DESs for long coronary lesions appears to be safe and more effective than the use of BMSs in terms of restenosis and adverse clinical events. SES use was associated with lower late luminal loss and a lower angiographic restenosis rate compared with PES use.

Beta-catenin overexpression augments angiogenesis and skeletal muscle regeneration through dual mechanism of vascular endothelial growth factor-mediated endothelial cell proliferation and progenitor cell mobilization.

OBJECTIVE: Beta-catenin plays a critical role in directing cell fate during embryogenesis, and uncontrollable activation leads to cancers, suggesting its importance in cell survival and proliferation. However, little is known regarding its role in endothelial cell (EC) and skeletal muscle proliferation and progenitor cell mobilization. METHODS AND RESULTS: Beta-catenin enhanced ECs proliferation, protected ECs from apoptosis, and increased the capillary forming capabilities, which was completely blocked by inhibition of its nuclear translocation. In addition, the increased proliferation by beta-catenin was associated with increased expression of cyclin E2. In skeletal myocytes, beta-catenin overexpression increased proliferation with cyclin D1 expression, decreased apoptosis, and induced hypertrophy. Furthermore, beta-catenin induced the expression of vascular endothelial growth factor (VEGF) in skeletal myocytes, resulting in EC proliferation. In a mouse hindlimb ischemia model, beta-catenin significantly increased recovery of blood perfusion, capillary density along with enhanced VEGF expression, and the number of proliferating ECs and myocytes. Local delivery of beta-catenin also promoted angiogenic progenitor cell mobilization and increased the number of satellite cells. CONCLUSIONS: Beta-catenin may be an important modulator of angiogenesis and myocyte regeneration not only by directly enhancing proliferation and survival of ECs and skeletal myocytes but also by inducing VEGF expression and promoting angiogenic progenitor cell mobilization and muscle progenitor cell activation.

Long-term clinical outcomes of dissections after intracoronary beta-radiation with rhenium-188-diethylene triamine penta-acetic acid-filled balloon system.

BACKGROUND: Intracoronary radiation with a rhenium-188 ((188)Re)-filled balloon is safe and efficiently reduces restenosis, but there is a potential risk of a (188)Re-filled balloon induced dissection. Little is known about the effect of radiation on dissection resolution and the late clinical outcome of dissection after brachytherapy. METHODS: After successful catheter-based treatments of de novo or restenotic lesion, 256 patients were randomly assigned to the radiation or control group. The (188)Re-filled balloon system was designed to deliver 17.6 Gy in 1.0-mm tissue depth. RESULTS: Dissections were identified in 15 patients among the 138 patients of the radiation group (10.9%). Additional stents were deployed in 10 patients to cover the flow-limiting dissection. Binary restenosis rate (53.3% vs. 16.3%, p=0.001) and target vessel revascularization (TVR) rate (53.3% vs. 11.1%, p<0.001) were significantly higher in patients with the dissection at 9 months. Geographic miss (GM) was identified in 4 of the 10 patients who underwent additional stenting. Binary restenosis rate in the GM group (100%; 4 of 4 patients) was significantly higher than the non-GM group (33.3%; 2 of 6 patients, p=0.02). Long-term follow-up of the patients with dissections who had not undergone TVR (n=7, mean follow-up duration: 640.7+/-387.3 days) has demonstrated persistent unhealed dissections. CONCLUSIONS: Intracoronary radiation impairs the healing process after vessel injury and residual dissection after brachytherapy leads to adverse clinical outcomes, which was mainly due to GM in case of stent implantation.

Impact of the maze operation combined with left-sided valve surgery on the change in tricuspid regurgitation over time.

BACKGROUND: Atrial fibrillation (AF) has been reported to be a predisposing factor for the progression of TR in patients with previous mitral or combined mitral/aortic valve surgery. We hypothesized that the maze operation (MAZE) can prevent the progression of tricuspid regurgitation (TR) in these patients. METHODS AND RESULTS: We analyzed 170 patients (age, 45.5+/-10.9 years) who had undergone mitral or combined mitral/aortic valve surgery. On the basis of preoperative rhythm, patients were divided into 3 groups; GrI was composed of 44 patients with sinus rhythm, GrII of 48 who had undergone MAZE, and GrIII of 78 with AF who had not undergone MAZE. Echocardiographic examinations were performed before, immediately after, and 92.2+/-17.2 (range, 50 to 131) months after surgery. Preoperative and immediate postoperative clinical and echocardiographic parameters were similar among the groups. Insignificant TR at the immediate postoperative examination worsened with time in 7.3% of GrI (3 of 41), 12.8% of GrII (6 of 47), and 38.8% of GrIII (26 of 67) patients at the final examination (P=0.63 for GrI versus GrII, P=0.001 for GrI versus GrIII, P=0.005 for GrII versus GrIII). The incidence of significant TR at the final echocardiographic examination was higher in GrIII (39.7%) compared with GrI (9.1%) and GrII (14.6%) (P=0.001 for GrI versus GrIII, P=0.005 for GrII versus GrIII), whereas GrI and GrII did not show any difference (P=0.63). By multivariate analysis, the only factor identified to prevent TR progression was the group factor (GrI and GrII versus GrIII, P=0.002 and P=0.005, respectively). In a subgroup analysis of GrII according to the presence or absence of atrial mechanical activity, the absence of atrial mechanical activity was identified as an independent parameter for the progression of TR (P=0.001). CONCLUSIONS: AF predisposes patients undergoing mitral valve surgery to the progression of TR, which can be prevented by MAZE. This additional benefit of MAZE is largely dependent on the restoration and maintenance of atrial mechanical function.

Effects of bone marrow derived mesenchymal stem cells transplantation in acutely infarcting myocardium.

BACKGROUND: Cellular cardiomyoplasty (CCM) is considered to be a novel therapeutic approach for post-myocardial infarction (MI) heart failure. In this study, the functional effects of cultured mesenchymal stem cells (MSCs) transplantation and the associated histopathologic changes were evaluated in a rat model of MI. METHODS: Rats were subjected to 5 h of coronary ligation followed by reperfusion and, 10 days after MI, animals were randomized into either the MSCs transplantation (MI-MSC, n=8) group or the control (n=8) group. Allogeneic MSCs (3x10(6) cells) or media were epicardially injected into the center and the border area of the infarct scar. RESULTS: Four weeks after the MSCs transplantation, the echocardiogram showed preserved anterior regional wall motion and increases in fractional shortening in the MI-MSC heart relative to the control heart. Left ventricular (LV) end-diastolic pressure was smaller in the MI-MSC than in the control group. Implanted MSCs formed islands of cell clusters on the border of the infarct scar, and the cells were positively immunostained by sarcomeric alpha-actinin and cardiac troponin T. In addition, the number of microvessels on the border area of the infarct scar was greater in the MI-MSC than in the control group. CONCLUSION: Allogeneic MSCs transplanted into the MI scar formed clusters of cell grafts on the border of the infarct, expressed cardiac muscle proteins, increased microvessel formation, and improved regional and global LV function. Our data indicate that CCM using MSCs may have a significant role in the treatment of post-MI heart failure.

Physiologic assessment of jailed side branch lesions using fractional flow reserve.

OBJECTIVES: This study was performed to evaluate the feasibility of the physiologic assessment of jailed side branches using fractional flow reserve (FFR) and to compare the measured FFR with the stenosis severity assessed by quantitative coronary angiography (QCA). BACKGROUND: It is not well-known which side branches should be treated after stent implantation at main branches and how to assess the functional significance of these lesions. METHODS: Ninety-seven jailed side branch lesions (vessel size > 2.0 mm, percent stenosis > 50% by visual estimation) after stent implantation at main branches were consecutively enrolled. The FFR was measured using a pressure wire at 5 mm distal and proximal to the ostial lesion of the jailed side branch. RESULTS: The FFR measurement was successful in 94 lesions. Mean FFRs were 0.94 +/- 0.04 and 0.85 +/- 0.11 at the main branches and jailed side branches, respectively. There was a negative correlation between the percent stenosis and FFR (r = -0.41, p < 0.001). However, no lesion with < 75% stenosis had FFR < 0.75. Among 73 lesions with > or = 75% stenosis, only 20 lesions were functionally significant. CONCLUSIONS: The FFR measurement in jailed side branch lesions is both safe and feasible. Quantitative coronary angiography is unreliable in the assessment of the functional severity of jailed side branch lesions, and measurement of FFR suggests that most of these lesions do not have functional significance.

Novel index of coronary collateral development as a useful predictor of clinical outcome in type 2 diabetic patients with coronary artery disease.

BACKGROUND: There is a paucity of information regarding the impact of the coronary collaterals on prognosis in type 2 diabetic (T2DM) patients. We developed a novel index, which considers not only the degree of collateral circulation but also the stimulus of collateral development, and investigated its prognostic value in T2DM patients with coronary artery disease (CAD). METHODS AND RESULTS: One hundred and ninety four consecutive T2DM patients were analyzed and followed for an average of 30 months. We measured the diameter stenosis (DS; %), corrected TIMI frame count (CTFC) and Rentrop score at 3 major epicardial coronary arteries. The collateral development (CD) score was calculated by: (Sigma Rentrop score +1)/Sigma [DS (%) x CTFC] x1,000. During the follow-up, acute cardiovascular events occurred in 49 patients. By multivariate analysis, the CD score was an independent predictor of adverse events not only in the total population (p<0.001), but in all 3 subgroups (p=0.020 for coronary artery bypass grafting, p=0.030 for percutaneous transluminal coronary angioplasty (PTCA) and p=0.003 for the medical group). Furthermore, patients in the tertile with the highest CD score showed improved survival by Kaplan-Meier analysis in the total population, the PTCA and the medical group. CONCLUSIONS: The CD score, a novel index of collateral development, may be a useful predictor of clinical outcome in T2DM patients with CAD.