Acute kidney injury after transcatheter aortic valve implantation and mortality risk-long-term follow-up.

BACKGROUND: Acute kidney injury (AKI) complicating transcatheter aortic valve implantation (TAVI) is relatively frequent and associated with significant morbidity. Previous studies have shown a higher 30-day and 1-year mortality risk in patients with periprocedural AKI. Our aim was to identify the prognostic impact of periprocedural AKI on long-term follow-up. METHODS: This is a single-center prospective study evaluating patients undergoing TAVI for severe aortic stenosis. AKI was defined according to the Valve Academic Research Consortium 2 definition, as an absolute increase in serum creatinine ≥0.3 mg/dL or an increase >50% within the first week following TAVI. Mortality data were compared between patients who developed AKI and those who did not. Logistic and Cox regressions were used for survival analysis. RESULTS: The final analysis included 1086 consecutive TAVI patients. AKI occurred in 201 patients (18.5%). During the follow-up period, 289 patients died. AKI was associated with an increased risk of 30-day mortality {4.5 versus 1.9% in the non-AKI group; hazard ratio [HR] 3.70 [95% confidence interval (CI) 1.35-10.13]}. Although 1-year mortality was higher in the AKI group in univariate analysis, it was not significant after a multivariate regression. AKI was a strong predictor of longer-term mortality [42.3 versus 22.7% for 7-year mortality; HR 1.71 (95% CI 1.30-2.25)]. In 189 of 201 patients we had data regarding recovery from AKI up to 30 days after discharge. In patients with recovery from AKI, the mortality rate was lower (38.2 versus 56.6% in the nonrecovery group; P = 0.022). CONCLUSIONS: Periprocedural AKI following TAVI is a strong risk factor for short-term as well as long-term mortality (up to 7 years). Therefore more effort is needed to reduce this complication.

Variance in Biomarker Usefulness as Indicators for Carotid and Coronary Atherosclerosis.

BACKGROUND: Atherosclerosis is a systemic disease. Nevertheless, the role of specific biomarkers as indicators for both coronary and carotid diseases is debatable. OBJECTIVES: To evaluate the association of biomarkers with coronary and carotid disease. METHODS: We studied 522 consecutive patients with stable angina. All underwent coronary angiography and carotid duplex study on the same day. Patients with no apparent carotid plaques were evaluated for carotid intima-media thickness (CIMT) using an automated system that sampled over 100 samples in each carotid artery. Biochemical markers of cardiovascular disease risk were obtained at the time of coronary angiography, including serum lipid levels, hemoglobin A1C (HbA1c), white blood cell count, fibrinogen and high sensitivity C-reactive protein (hs-CRP). RESULTS: The mean age of the patients was 66 ± 11; 73% were males. Significant carotid stenosis was associated with higher hs-CRP (9.4 ± 17 vs. 6.3 ± 13 mg/L, P = 0.001), while high HbA1c (6.7 ± 1.6 vs. 5.8 ± 0.8%, P 0.001) and low high density lipoprotein levels (40 ± 9 vs. 47 ± 14 mg/dl, P < 0.001) were linked with advanced coronary artery disease severity. In contrast, CIMT was not related to any of the biomarkers evaluated. CONCLUSIONS: Although atherosclerosis is considered a systemic disease, different biomarkers are associated with coronary and carotid artery disease. Identifying the specific biomarkers for each disease is important for both prevention and for exposing the underlying pathophysiologic mechanism.

High red blood cell distribution width and preclinical carotid atherosclerosis.

BACKGROUND: Preclinical carotid atherosclerosis is associated with future risk of stroke. Data regarding the correlation between carotid atherosclerosis and biomarkers, which might predict the risk for the disease has been inconsistent and conflicting. Red blood cell distribution width (RDW) is also related to adverse clinical outcomes. Studies examining the relationship between RDW and preclinical and clinical carotid atherosclerosis were non-conclusive. OBJECTIVE: To study the association between RDW and preclinical carotid atherosclerosis in a large heterogeneous cohort. METHODS: Patients underwent Doppler ultrasound of the common carotid artery and Carotid Intima Media Thickness (CIMT). Advanced CIMT software analyzed over 100 samples in each exam. Blood samples for RDW were obtained on the same day. Logistic regression was used to evaluate the correlation between RDW and preclinical carotid atherosclerosis. RESULTS: Five hundred and twenty-two consecutive patients were included, with a mean age of 6.6 ± 11. A cut-off value of 14.1% was used to differentiate between high and low RDW groups. The higher RDW group (RDW above 14.1%) was significantly older and with more cardiovascular risk factors. In a multivariate analysis, in all the patients including those treated by lipid modifying therapies, high RDW was significantly associated with advanced CIMT (OR = 2.35, CI 95% 1.28-4.30, p = 0.006). This association remained significant in subgroups of non-diabetic patients as well as patients not treated by lipid modifying drugs. RDW was also associated with significant carotid artery stenosis (OR = 1.77, CI 95% 1.12-2.82, p = 0.015). CONCLUSIONS: High RDW correlates with increased risk for preclinical and clinical carotid atherosclerosis.

Anemia in ST-Elevation Myocardial Infarction Patients with Markers of Inadequate Bone Marrow Response.

BACKGROUND: Anemia confers an adverse prognosis in patients with ST-elevation myocardial infarction (STEMI). Several mechanisms have been implicated in the etiology of anemia in this setting, including inflammation, blood loss, and the presence of comorbidities such as renal failure. OBJECTIVES: To evaluate the adequacy of bone marrow response as potentially reflected by elevation in blood and reticulocyte counts. METHODS: Consecutive men with STEMI who underwent primary percutaneous intervention within 6 hours of symptom onset and who presented to our catheterization laboratory during a 36 month period were included in the study. The cohort was divided into quartiles according to hemoglobin concentration, and differences in clinical and laboratory characteristics between the groups were evaluated. RESULTS: A total of 258 men with STEMI were recruited, 22% of whom suffered from anemia according to the World Health Organization classification (hemoglobin < 13 g/dl). Men in the lowest quartile of hemoglobin concentration presented with significantly lower white blood cell and platelet counts (9.6 ± 2.9 vs. 12.6 ± 3.6 x 103/µl, P < 0.001) and (231 ± 79 vs. 263 ± 8 x 103/µl, P < 0.01), respectively, despite higher inflammatory biomarkers (C-reactive protein and fibrinogen) compared with patients in the upper hemoglobin concentration quartile. Reticulocyte production index was not significantly higher in anemic patients, with a value of 1.8, 1.4, 1.5 and 1.6 in the ascending hemoglobin quartiles, respectively (P = 0.292). CONCLUSIONS: Anemic men with STEMI have relatively lower leukocyte and platelet counts as well as a reduced reticulocyte count despite higher inflammatory biomarkers. These findings might suggest inadequate bone marrow response.

Decline in serum cholinesterase activities predicts 2-year major adverse cardiac events.

Parasympathetic activity influences long-term outcome in patients with cardiovascular disease, but the underlying mechanism(s) linking parasympathetic activity and the occurrence of major adverse cardiovascular events (MACEs) are incompletely understood. The aim of this pilot study was to evaluate the association between serum cholinesterase activities as parasympathetic biomarkers and the risk for the occurrence of MACEs. Cholinergic status was determined by measuring the cumulative capacity of serum acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) to hydrolyze the AChE substrate acetylthiocholine. Cholinergic status was evaluated in randomly selected patients undergoing cardiac catheterization. The patients were divided into two groups of 100 patients in each group, with or without occurrence of MACEs during a follow-up period of 40 months. Cox regression models adjusted for potential clinical, metabolic and inflammatory confounders served to evaluate association with clinical outcome. We found that patients with MACE presented lower cholinergic status and AChE values at catheterization (1,127 ± 422 and 359 ± 153 nmol substrate hydrolyzed per minute per milliliter, respectively) than no-MACE patients (1,760 ± 546 and 508 ± 183 nmol substrate hydrolyzed per minute per milliliter, p < 0.001 and p < 0.001, respectively), whose levels were comparable to those of matched healthy controls (1,622 ± 303 and 504 ± 126 nmol substrate hydrolyzed per minute per milliliter, respectively). In a multivariate analysis, patients with AChE or total cholinergic status values below median showed conspicuously elevated risk for MACE (hazard ratio 1.85 [95% confidence interval [CI] 1.09-3.15, p = 0.02] and 2.21 [95% CI 1.22-4.00, p = 0.009]) compared with those above median, even after adjusting for potential confounders. We conclude that parasympathetic dysfunction expressed as reduced serum AChE and AChE activities in patients compared to healthy controls can together reflect impaired parasympathetic activity. This impairment predicts the risk of MACE up to 40 months in such patients. Monitoring these parasympathetic parameters might help in the risk stratification of patients with cardiovascular disease.

Red blood cell distribution width and 3-year outcome in patients undergoing cardiac catheterization.

Red blood cell distribution width (RDW), which is routinely reported in complete blood counts, is a measure of the variability in size of circulating erythrocytes. RDW is a novel, independent predictor of prognosis in patients with cardiovascular diseases. The aim of the present study was to evaluate the significance of this biomarker in a relatively large cohort of patients, and to assess its association with a more severe underlying cardiovascular disease. A cohort of 3,222 consecutive patients undergoing coronary angiography was divided according RDW median. The association between RDW and 3-year outcome in the context of other predictors was assessed using Cox's proportional hazards analysis. Patients with elevated RDWs were older, had higher body mass indices, and had more cardiovascular risk factors and more cardiovascular diseases. The total rate of mortality, MI and stroke (MACE) was 7.7% (120 events) in the lower RDW group, and 18.2% (303 events) in the higher RDW group, p < 0.001. Following adjustment for multiple background risk factors, medications, and laboratory results, the RDW value was independently associated with worse outcome (HR = 1.12, 95% CI 1.07-1.18, p < 0.001, for each 1% increase in RDW). Elevated RDW values are independently associated with adverse 3-year outcome in patients undergoing coronary angiography.

Comparative efficacy analysis of an aspiration device before primary angioplasty in patients with acute myocardial infarction: a single-center experience.

BACKGROUND: ST-elevation myocardial infarction is caused by occlusive coronary thrombosis where antecedent plaque disruption occurs. When treating STEMI the main goal is to achieve prompt reperfusion of the infarction area. Several studies have demonstrated the efficacy of an aspiration device before percutaneous coronary intervention in patients with acute myocardial infarction. OBJECTIVES: To determine the added value of thrombus aspiration prior to primary PCI by comparing AMI patients with totally occluded infarct-related artery treated with routine primary PCI to those treated with extraction device prior to primary PCI. METHODS: The study group comprised 122 consecutive patients with AMI and a totally occluded infarct artery (TIMI flow 0) who underwent primary PCI. The patients were divided into two groups: 68 who underwent primary PCI only (control group) and 54 who underwent primary thrombus extraction with an extraction device before PCI (extraction group). Baseline clinical and lesion characteristics were similar in both groups. Final TIMI grade flow and myocardial blush as well as 1 year mortality, target lesion revascularization, recurrent myocardial infarction, unstable angina and stroke were compared between the two groups. RESULTS: Primary angiographic results were better for the extraction group versus the control group: final grade 3 TIMI flow was 100% vs. 95.6% (P= 0.03) and final grade 3 myocardial blush grade 50% vs. 41.18% (although Pwas not significant). Long-term follow-up total MACE showed a nonsignificant positive trend in the extraction group (12.96% vs. 24.71%, P= 0.26). CONCLUSIONS: The use of extraction devices for intracoronary thrombectomy during primary PCI in patients with totally occluded infarct artery significantly improved epicardial reperfusion in the infarct-related vessel and showed a trend for more favorable long-term outcome.

Prevention of post procedural acute kidney injury in the catheterization laboratory in a real-world population.

BACKGROUND: Radiologists and cardiologists have a remarkably different approach to the clinical importance and to the need for prophylactic treatment of contrast-induced acute kidney injury (CI-AKI). OBJECTIVES: To evaluate the efficacy of forced diuresis with matched controlled hydration (FMH) in a real-world, high risk population. METHODS: This is an investigator-driven, single-center, retrospective analysis of prospectively collected data. A total of 150 consecutive patients undergoing coronary angiography, angioplasty or TAVR who were treated with FMH were compared to a matched historical control cohort. RESULTS: In the FMH treated patients, eGFR improved following the procedure from 37ml/min per 1.73m2 at baseline to 39ml/min per 1.73m2 (p<0.001); the net creatinine decreased from 1.85mg/dl to 1.78mg/dl (p<0.001). Among the matched control group, eGFR deteriorated from a baseline value of 36.7ml/min per 1.73m2 to 33.2ml/min per 1.73m2 post procedurally (p<0.001); the net creatinine increased from 1.88mg/dl to 2.14mg/dl (p<0.001). The incidence of post procedural AKI was substantially lower in the FMH treated group (2.7%) compared to the control group (26.7%). By multivariable analysis FMH treatment was independently correlated with reduced incidence of post procedural AKI compared with the control group (OR 0.06, p<0.001). Contrast volume did not correlate with AKI in neither univariate nor multivariate analyses. CONCLUSIONS: In patients undergoing coronary angiography, angioplasty or TAVR, who are considered high risk to develop post procedural AKI, forced diuresis with matched controlled hydration resulted in a significant net creatinine decrease, eGFR increase and a decrease in the incidence of AKI.

Comparison between multivessel stenting with drug eluting to the LAD and bilateral internal thoracic artery grafting.

BACKGROUND: Reduction of restenosis and reinterventions was reported with drug-eluting stents (Cypher). This study compares results of multivessel Cypher stenting with bilateral internal thoracic artery (BITA) grafting. METHODS: From January 2002 to June 2004, 725 consecutive patients underwent multivessel myocardial revascularization, 95 by 2 or more Cypher stents and 630 by BITA. After matching for age, sex, and extent of coronary artery disease, 2 groups (87 patients each) were used to compare the 2 revascularization modalities. RESULTS: The 2 groups were similar; however, left main and the use of an intra-aortic balloon pump were more prevalent in the BITA group. The number of coronary vessels treated per patient was higher in the BITA group (2.71 versus 2.24 for BITA and Cypher, respectively; P = .001). Mean follow-up was 12 months. Thirty-day mortality was 0 in both groups. There were no late deaths in the BITA group and 2 (2.3%) in the Cypher group (P value was not significant). Angina returned in 29.9% of the Cypher group and 12.6% of the BITA group (P = .005). Multivariable Cox analysis revealed percutaneous intervention (PCI) (Cypher group) to be the only independent predictor of angina recurrence (Odds Ratio 2.62, 95% Confidence Interval 1.11-6.17). There were 10 reinterventions (PCI) in the Cypher group compared to 5 in the BITA group. One-year reintervention-free survival (Kaplan-Meier) of the BITA group was 96% compared to 88% in the Cypher group (P = .015). CONCLUSIONS: Midterm clinical outcome of surgically treated patients is still better. However, the reintervention gap between surgery and percutaneous interventions was reduced by treating 2 or more coronary vessels with Cypher stents.

Functional inhibition of Ras by S-trans,trans-farnesyl thiosalicylic acid attenuates atherosclerosis in apolipoprotein E knockout mice.

BACKGROUND: Atherosclerosis is a multifactorial disorder involving inflammatory processes. These responses are associated with robust activation of signaling cascades by diverse cell surface receptors in a variety of cell types. The processes that are involved in atherosclerosis would likely require intact Ras pathways, which play a key role in the control of cell growth, differentiation, and apoptosis. METHODS AND RESULTS: We examined whether the Ras inhibitor farnesyl thiosalicylic acid (FTS) can suppress atherogenesis in the apolipoprotein E-deficient mouse model. Mice were treated with FTS or a control regimen 3 times weekly for 6 weeks and fed a normal chow diet. Two additional groups included FTS-treated and control-treated mice that were fed a high-fat diet for 10 weeks. FTS reduced both fatty streaks and advanced lesions compared with the control treatment. Ras inhibition in vivo was evidenced by the reduced content of the active form of Ras (Ras-GTP) in aortas of FTS-treated mice. Splenocytes from the FTS-treated versus control mice exhibited reduced proliferation to oxidized LDL (OxLDL) but not to concanavalin A. IgG anti-OxLDL antibody levels were reduced in FTS-treated mice compared with controls. Whereas no effect of FTS was evident on plaque T lymphocyte and macrophage content, lesional vascular cell adhesion molecule-1 and nuclear factor-kappaB expression were considerably reduced compared with controls. CONCLUSIONS: FTS suppressed atherosclerotic plaques in apolipoprotein E-deficient mice, providing a useful tool for research in atherosclerosis.

Revascularization of left anterior descending coronary artery in patients with single and multivessel disease: comparison between off-pump internal thoracic artery and drug-eluting stent.

STUDY OBJECTIVES: The left anterior descending artery (LADA), particularly when the proximal segment of the vessel is involved, is a challenging area for percutaneous coronary interventions (PCIs); therefore, coronary artery bypass grafting is often considered and sometimes performed even in patients with single-vessel disease involving the LADA. This study compares mid-term results of LADA revascularization with a drug-eluting stent (DES), with off-pump coronary artery bypass grafting (OPCAB) in patients with single-vessel or multivessel coronary artery disease (CAD). DESIGN: Matched-groups, retrospective cohort comparison between the DES and OPCAB. PATIENTS: From June 2002 to December 2003, 354 patients underwent myocardial revascularization of the LADA by OPCAB, and 168 by DES. After matching for age, sex, and extent of CAD, two groups (116 patients each) were used to compare the two revascularization modalities. The groups were similar; however, an ejection fraction of <30%, old myocardial infarction, and use of an intraaortic balloon pump were more prevalent in the OPCAB group. RESULTS: The average number of coronary vessels treated per patient in the two groups was similar (OPCAB, 1.97; DES, 1.6; p = 0.581). The 30-day mortality rate was 0.9% in the OPCAB group and 0% in the DES group (p = 0.329). The mean duration of follow-up was 12 months. There was one late death in each group. Angina returned in 31% of patients in the DES group and in 11.2% of the patients in the OPCAB group (p = 0.001). There were 12 reinterventions in the DES group compared to three reinterventions in the surgical group (p = 0.020). The only independent predictor (Cox proportional hazards regression model) of the return of angina (risk ratio [RR], 3.36; 95% confidence interval [CI], 1.57 to 7.14) and reintervention (RR, 3.9; 95% CI, 1.34 to 11.24) was assignment to the DES group. CONCLUSIONS: The mid-term clinical outcome of OPCAB in patients with CAD, including multivessel disease, was better than that for PCIs with only one DES used in patients with similar extents of CAD.

Number and adhesive properties of circulating endothelial progenitor cells in patients with in-stent restenosis.

OBJECTIVE: Intact endothelialization machinery is essential to facilitate vessel healing after stent placement and to prevent restenosis. Circulating endothelial progenitor cells (EPC) have been demonstrated in the peripheral blood and shown to display endothelial functional properties, along with the ability to traffic to damaged vasculature. We reasoned that robust in-stent intimal growth could be partially related to impaired endothelialization resulting from reduced circulating EPC number or function. METHODS AND RESULTS: Sixteen patients with angiographically-demonstrated in-stent restenosis were compared with patients with a similar clinical presentation that exhibited patent stents (n=11). Groups were similar with respect to the use of drugs that could potentially influence EPC numbers. Circulating EPC numbers were determined by the colony-forming unit assay, and their phenotype was characterized by endothelial-cell markers. Adhesiveness of EPC from both groups to extracellular matrix and to endothelial cells was also assayed. Patients with in-stent restenosis and with patent stents displayed a similar number of circulating EPC. Fibronectin-binding was compromised in patients with in-stent restenosis as compared with their controls exhibiting patent stents. Patients with diffuse in-stent restenosis exhibited reduced numbers of EPC in comparison with subjects with focal in-stent lesions. CONCLUSIONS: Reduced numbers of circulating EPC in patients with diffuse in-stent restenosis and impaired adhesion of EPC from patients with restenosis provides a potential mechanism mediating the exuberant proliferative process. These markers, if further validated, could provide means of risk stratifying patients for likelihood of developing in-stent restenosis.

Serum levels of interleukin-18 in patients with stable and unstable angina pectoris.

Recent evidence suggests that atherosclerosis is an inflammatory disorder in which cytokines appear to play an important role. Special attention centered over the possible contribution of cytokines to the destabilization of the plaque. IL-18 is a proinflammatory cytokine of the IL-1 family, recognized for its ability to promote IFN-gamma secretion. It has recently been detected in human plaques and its administration was associated with increased atherosclerosis in apolipoprotein E (apoE) mice concomitant with an increase in plaque infiltrating inflammatory cells. In our study, we investigated whether patients with established atherosclerosis, with either stable or unstable angina, possessed high levels of IL-18. Patients with stable angina (n=48) were from the outpatient clinic whereas patients with unstable angina (n=73) were recruited upon admission and prior to performance of coronary angiography. Control patients (n=19) were healthy subjects with no evidence of coronary artery disease. Serum levels of IL-18 were assayed by ELISA. Patients with stable and unstable angina exhibited higher serum levels of IL-18 (77.1+/-7.2 and 61.5+/-5.1 pg/ml, respectively) in comparison to control subjects (p=0.002 and p=0.02, respectively). However, levels of IL-18 did not differ significantly between patients with stable and unstable angina. No differences were evident in the serum concentrations of IL-18 in patients with unstable angina (n=17) upon admission and 1-3 months later when the angina was already controlled. Although IL-18 serum levels appear elevated in the presence of coronary atherosclerosis, there is no evidence to associate this progression towards plaque instability.

High red blood cell distribution width is associated with the metabolic syndrome.

OBJECTIVES: High values of Red Blood Cell Distribution Width (RDW) have been associated with adverse outcome in various clinical settings. The mechanism behind this association is not clear. The Metabolic Syndrome (MetS) is a chronic inflammatory disorder that increases the risk for cardiovascular disease and death. The aim of our study was to evaluate the association between high RDW and the MetS in a relatively large cohort of patients. METHODS: A cohort of 3,529 consecutive patients undergoing coronary angiography was used to evaluate the association between RDW and the MetS. The association was assessed by using a logistic regression. Cox's regression analysis was used to evaluate the impact of RDW on long term mortality. RESULTS: The mean age was 65 years (range 24-97), with 27% women. Overall, 30% were diagnosed with metabolic syndrome. The prevalence of MetS was 29% in patients with RDW <14% and 34% in patients with RDW ≥14% (P = 0.003).Using multivariate analysis, RDW values above 14% were independently associated with MetS (odds ratio 1.2 [95% CI 1.0-1.4], P = 0.043). Among all the criteria of the metabolic syndrome, hypertension, elevated glucose levels and abdominal obesity were associated with high RDW, with hypertension being the strongest criteria, with an increased risk of 1.8 fold ([95% CI 1.5-2.1]; P = 0.001). During follow up (1614 ± 709 days, 2-2763 days), long term mortality was 8% in the low RDW group and 28% in the high RDW group (p < 0.001). CONCLUSION: RDW ≥14% is independently associated with higher rates of metabolic syndrome and long-term all-cause mortality.

Relation of metabolic syndrome with long-term mortality in acute and stable coronary disease.

Past studies examining the effects of the metabolic syndrome (MS) on prognosis in postangiography patients were limited in size or were controversial in results. The aim of the study was to examine the association of the MS and the risk for long-term mortality in a large cohort of patients undergoing coronary angiography for various clinical indications. Medical history, physical examination, and laboratory values were used to diagnose patients with the MS. Cox regression models were used to analyze the effect of MS on long-term all-cause mortality. We prospectively recruited 3,525 consecutive patients with a mean age of 66 ± 22 years (range 24 to 97) and 72% men. Thirty percent of the cohort had MS. Patients with MS were more likely to have advanced coronary artery disease and acute coronary syndrome (p <0.001). Patients with MS had more abnormalities in their metabolic and inflammatory biomarkers regardless of their clinical presentation. A total of 495 deaths occurred during a mean follow-up period of 1,614 ± 709 days (median 1,780, interquartile range 1,030 to 2,178). MS was associated with an increased risk of death in the general cohort (hazard ratio [HR] 1.27, 95% confidence interval [CI] 1.01 to 1.56, p = 0.02). MS had a significant effect on mortality in stable patients (HR 1.55, 95% CI 1.1 to 2.18, p = 0.01), whereas it did not have a significant effect on mortality in patients with acute coronary syndrome (HR 1.11, 95% CI 0.86 to 1.44, p = 0.42). In conclusion, MS is associated with increased mortality in postangiography patients. Its adverse outcome is mainly seen in patients with stable angina.

Nonobstructive aortic valve calcification: a window to significant coronary artery disease.

BACKGROUND: Aortic valve calcification without obstruction (AVC) is common in the elderly and is associated with increased cardiovascular mortality and morbidity. We hypothesized that AVC detected by transthoracic echocardiography (TTE) is a marker for significant coronary artery disease in patients undergoing coronary angiography. METHODS: The study group included 388 patients with AVC (259 males, 129 females; mean age 72.2+/-9 years) who underwent coronary angiography for various indications. Data were compared with 320, age- and sex-matched patients without AVC who underwent coronary angiography for the same indications. AVC was detected in TTE as focal areas of increased echogenicity and thickening of the aortic-valve leaflets without restriction in motion. Significant obstructive coronary artery disease was defined as either a > or = 70% reduction of the internal diameter of the left anterior descending, right coronary, or left circumflex artery distribution or a > or = 50% reduction of the internal diameter of the left main coronary artery. Risk factors for atherosclerosis including hypertension, smoking, hypercholesterolemia and diabetes were also investigated. RESULTS: Compared with control group, the AVC group had a higher prevalence of significant coronary artery disease (90 vs. 85%, P=0.019), and a trend for lower frequency of coronary arteries without obstruction (6 vs. 9%, P=0.l1); a trend was also noted for 3-vessel disease (38 vs. 33%, P=0.14). Multivariate analysis identified age (P=0.000l), sex (P=0.000l), hypercholesterolemia (P=0.005) and AVC (P=0.02) as independent predictors for significant coronary artery disease. CONCLUSIONS: There is a significant association between AVC and significant coronary artery disease in patients undergoing coronary angiography. Thus AVC can serve as a window to atherosclerosis of the coronary arteries. These results reinforce a previous observation regarding association between AVC and increased risk of cardiovascular morbidity.

L-arginine attenuates lymphocyte activation and anti-oxidized LDL antibody levels in patients undergoing angioplasty.

BACKGROUND: Patients with acute coronary syndromes exhibit evidence of peripheral T lymphocyte activation, elevated acute phase proteins and enhanced oxidative stress. Nitric oxide (NO) has been recognized as one of the relaxant factors synthesized and released by normal endothelium, and acts as a double-edged sword on the immune system. L-arginine ameliorates experimental atherosclerosis and restenosis as well as endothelial dysfunction. We sought to investigate the effect of L-arginine administration on the extent of lymphocyte activation and anti-oxLDL antibodies in patients with unstable angina undergoing PCI with stent placement. METHODS: Patients with unstable angina were randomized to treatment with L-arginine (6g per day; n = 13) or none (n = 16) for 1 month starting immediately on the day of stent deployment. Lymphocyte activation was assayed by FACS employing double staining with a common lymphocyte marker (CD3) and an activation marker HLA-DR, on the day of the procedure and 1 month later. Anti-oxLDL antibodies were assayed by ELISA. RESULTS: Patients with unstable angina not receiving L-arginine exhibited a significant 43% rise in the percentage of activated peripheral T lymphocytes, 1 month after stent deployment. Patients treated with L-arginine exhibited a fall albeit not significant in the fraction of peripheral lymphocytes bearing the activation marker. Antibodies to anti-oxLDL rose significantly between baseline and 1 month follow-up. L-arginine treatment significantly attenuated the rise in anti-oxLDL antibody levels. CONCLUSION: L-arginine attenuates the systemic rise in peripheral lymphocyte activation and oxidative stress markers induced by vessel wall injury following PCI. These effects may contribute to a favorable effect of the drug in patients with acute coronary syndromes undergoing PCI.

The right internal thoracic artery and right gastroepiploic artery: alternative sites for proximal anastomosis in patients with atherosclerotic calcified aorta.

BACKGROUND: Atherosclerotic or calcified ascending aorta is an important predictor of adverse cerebrovascular events. Using off-pump coronary artery bypass (OPCAB) with composite and in situ arterial grafting to avoid aortic manipulation and clamping may reduce the risk of stroke related to aortic atheroembolism. When the aorta is calcified and cannot serve as a safe site for proximal anastomosis, this anastomosis can be performed on the proximal segment of the right internal thoracic artery (ITA) and right gastroepiploic artery (RGEA). Four such cases are described. METHODS: In 2 patients, the proximal right ITA was used as the site for proximal saphenous vein graft (SVG) anastomosis. Chronic obstructive lung disease in one patient and insulin-dependent diabetes in the other precluded performance of OPCAB with bilateral ITA. In addition, positive Allen test precluded performance of composite T-graft with radial artery (RA) on ITA. Both SVGs were anastomosed distally to the posterior descending artery. In 2 other patients, RA was connected end-to-side to the proximal segment of the RGEA. Both of these patients had repeat operations. The distal end of the RGEA was too small, and concerns regarding the future flow to a very large coronary bed precluded its use as an in situ graft. RESULTS: All patients underwent the operative procedures without any neurological or cardiovascular adverse effects, and all are midterm, symptom-free survivors. Postoperative graft patency was confirmed intraoperatively with flow measurements and postoperatively with control angiography or coronary imaging computed tomography. CONCLUSIONS: The RITA and proximal RGEA can serve safely as sites for proximal anastomosis in patients with atherosclerotic calcified aorta undergoing OPCAB.

Revascularization of the left anterior descending artery with drug-eluting stents: comparison with arterial off-pump surgery.

BACKGROUND: This study compared early results of left anterior descending artery (LAD) stenting using drug-eluting stents (Cypher) with off-pump bilateral internal thoracic arterial (BITA) grafting. METHODS: From June 2002 to June 2003, 200 consecutive patients underwent myocardial revascularization of the LAD territory, 100 by Cypher and 100 by BITA. The 2 groups were similar; however, left main disease and triple-vessel disease (20% and 75% versus 2% and 28%), age >70 (36% versus 17%) and intraaortic balloon pump (7% versus 0%) were more prevalent in the BITA group, and prior percutaneous coronary angiogplasty to the LAD was more prevalent in the Cypher group (28% versus 16%). RESULTS: The number of coronary vessels treated per patient in the BITA group was higher (2.7 versus 1.45, P < .01). Thirty-day mortality was 1% in the BITA group and 0% in the Cypher group. Mean follow-up was 12 months. There was 1 late death in each group. Angina returned in 32% of the Cypher group and in 1% of the BITA group. There were 9 reinterventions in the Cypher group: 7 coronary angioplasties (including 2 to the LAD) and 2 surgical interventions. There was neither recurrent angina nor reintervention in the surgical group. CONCLUSIONS: Despite a higher risk profile of patients treated with BITA, their clinical outcome is better. A longer and more complete angiographic follow-up is required to determine the role of drug-eluting stents in LAD revascularization.