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Markers of Inflammation and Rapid Coronary Artery Disease Progression in Patients With Stable Angina Pectoris

Background—Both endothelial cell activation and macrophage activation play a significant role in atherogenesis and atheromatous plaque vulnerability and may determine rapid coronary artery disease (CAD) progression. We sought to assess the association between serum inflammatory markers and rapid CAD progression in patients with chronic stable angina pectoris. Methods and Results—We studied 124 chronic stable angina pectoris patients (84 men; mean age, 61±10 years) who were on a waiting list for coronary angioplasty for a mean time of 4.8±2.4 months. CAD progression was defined as ≥10% diameter reduction of a pre-existing stenosis ≥50%, ≥30% diameter reduction of a stenosis <50%, development of a new stenosis ≥30% in a previously normal segment, or progression of any stenosis to total occlusion. CAD progression occurred in 35 patients (28%). After adjustment with binary logistic regression, neopterin (P<0.001), high-sensitivity C-reactive protein (P=0.017), matrix metalloproteinase-9 (P=0.002), soluble intercellular adhesion molecule 1 (P<0.001), and previous history of unstable angina (P=0.01) were independent predictors of rapid CAD progression. The association between rapid disease progression and inflammatory markers remained significant even when presence of complex lesions was introduced into the multivariate model. Conclusions—Rapid CAD progression in patients with stable angina pectoris is associated with increased C-reactive protein levels and raised concentrations of biochemical markers of endothelial and macrophage activation.

CD14 and toll-like receptor 4: a link between infection and acute coronary events?

The CD14 receptor is a pattern recognition molecule in the innate immune response against microorganisms and other exogenous and endogenous stress factors. The most important CD14 signalling co-receptor is toll-like receptor 4 (TLR4), which activates, among others, the nuclear factor κB (NF-κB) inflammatory pathway. Besides its role in innate immunity and host defence, the proinflammatory cytokines expressed upon TLR4/NF-κB pathway activation exert proatherogenic effects. The CD14 C(–260)T promoter and TLR4 Asp299Gly functional polymorphisms have been recently implicated in the development of cardiovascular events, suggesting that the genetically determined inflammatory response against pathogens or their antigens may have a major role in atherogenesis and subsequent acute events. Is the association of these polymorphisms with cardiovascular disease more evidence for the implication of infection, especially by Gram negative bacteria, in the development of acute coronary events? This article reviews the molecular basis, biological functions, and clinical implications of the CD14/TLR4 polymorphisms in the development of cardiovascular events.

Relation of ischemia-modified albumin (IMA) levels following elective angioplasty for stable angina pectoris to duration of balloon-induced myocardial ischemia

The results in this study confirm and expand previous reports that ischemia-modified albumin (IMA) is an early marker of ischemia in the setting of percutaneous coronary intervention (PCI). We observed that IMA levels are related to the number of inflations, inflation pressure, and duration of inflations. It is therefore likely that IMA reflects the magnitude and duration of ischemia induced during PCI.

Atrioventricular Conduction Disturbance Characterization in Transcatheter Aortic Valve Implantation With the CoreValve Prosthesis

Background— Atrioventricular (AV) block is one of the most frequent complications of CoreValve transcatheter aortic valve implantation (TAVI). The aim of this study was to analyze the effects of CoreValve implantation on AV conduction. Methods and Results— Electrophysiological study was performed immediately before and after CoreValve implantation in 18 consecutive, permanent pacemaker-free patients. An electrode was placed on the His bundle during valve implantation, and data were continuously recorded during the procedure. With surface ECG, a median (first, third quartile) QRS width of 96 (84, 116) to 150 (121, 164) ms (P=0.001) and PR interval of 180 (159, 216) to 210 (190, 240) ms (P=0.008) were significantly prolonged, and QRS axis was left deviated 30° (−32°, 46°) to −20° (−60°, 2°) (P=0.005). With intracardiac electrograms, the AH (97 [70, 123] to 115 [96, 135] ms, P=0.021) and HV (52 [42, 55] to 60 [50, 70] ms, P=0.002) intervals were increased. At the end of the procedure, we observed significant ECG- or electrophysiological study-persistent conduction disturbances in 14 (78%) patients. Five patients experienced transient changes (2 AV blocks and 3 left bundle branch blocks). Conclusions— CoreValve implantation worsens AV conduction in most patients, either transiently or permanently. This worsening is the result of direct damage either on the His bundle or on the AV node.

Percutaneous implantation of the CoreValve self-expanding aortic valve prosthesis in patients with severe aortic stenosis: early experience in Spain.

INTRODUCTION AND OBJECTIVES The aim of the study was to describe early experience and medium-term follow-up with the CoreValve self-expanding aortic prosthesis at three Spanish hospitals. METHODS The study included patients with severe symptomatic aortic stenosis. Other inclusion criteria were: aortic valve area <1 cm(2) (<0.6 cm(2)/m(2)); aortic valve annulus diameter in the range 20-27 mm; diameter of the ascending aorta at the level of the sinotubular junction < or = 40 mm (small prosthesis) or < or = 43 mm (large prosthesis), and femoral artery diameter >6 mm. RESULTS The study included 108 patients with a mean age of 78.6 + or - 6.7 years, a mean aortic valve area of 0.63 + or - 0.2 cm(2) and a mean logistic EuroSCORE of 16% + or - 13.9% (range, 2.27%-86.4%). After valve implantation, the maximum echocardiographic transaortic valve gradient decreased from 83.8 + or - 23 to 12.6 + or - 6 mmHg. No patient presented with greater than grade-2 residual aortic regurgitation on angiography. The procedural success rate was 98.1%. No patient died during the procedure. Definitive pacemaker implantation was carried out for atrioventricular block in 38 patients (35.2%). At 30 days, all-cause mortality and the rate of the combined endpoint of death, stroke, myocardial infarction or referral for surgery were 7.4% and 8.3%, respectively. The estimated 1-year survival rate calculated using the Kaplan-Meier method was 82.3% (for a median follow-up period of 7.6 months). CONCLUSIONS Our early experience indicates that percutaneous aortic valve replacement is a safe and practical therapeutic option for patients with severe aortic stenosis who are at a high surgical risk.

The role of melatonin in acute myocardial infarction

Melatonin, a circadian hormone with marked antioxidant properties, has been shown to protect against ischemia-reperfusion myocardial damage, especially when administered during reperfusion period. Melatonin has cardioprotective properties via its direct free radical scavenging and its indirect antioxidant activity. Melatonin efficiently interacts with various reactive oxygen and reactive nitrogen species and it also upregulates antioxidant enzymes and downregulates pro-oxidant enzymes. In addition, melatonin demonstrated blood pressure lowering, lipid profile normalizing and anti-inflammatory properties. The lack of these cardioprotective effects due to insufficient melatonin levels might be associated with several cardiovascular pathologies including ischemic heart disease. Patients with acute coronary syndrome or after myocardial infarction were shown to have reduced nighttime melatonin levels and 6-sulfatoxymelatonin urinary excretion. These alterations might translate to increased cardiovascular risk observed in acute myocardial infarction patients with low melatonin levels; and a mutation in melatonin receptors might augment the risk for acute myocardial infarction. Therefore, it is expected that melatonin administration could play a clinically relevant role in the pharmacotherapy of ischemic heart disease; an assumption supported by low toxicity and high safety of melatonin.

Prevalence and outcome of newly detected diabetes in patients who undergo percutaneous coronary intervention

AIMS The beneficial effect of specific measures in patients with newly detected diabetes during percutaneous coronary intervention (PCI) has been poorly studied. Here, we determined the prevalence of newly detected diabetes in a cohort of patients who underwent PCI and analysed their clinical outcome. METHODS AND RESULTS A prospective study included patients without previous diagnosis of diabetes that were referred for PCI between November 2005 and May 2006. Major cardiac events were registered after admission and during 12 months of follow-up, and oral glucose tolerance was tested at 15 days after hospital discharge. Six hundred and sixty-two consecutive patients were referred to our hospital for PCI. The distribution of the glycometabolic state of the entire population was (95% CI): known diabetes 28.8% (25.2-32.6), newly detected diabetes 16.2% (13.1-19.8), impaired glucose tolerance 24.5% (20.8-28.5), impaired fasting glucose 1% (0.4-2.4), and normal glucose regulation 29.5% (25.5-33.7). In a multivariable analysis, the presence of newly detected diabetes was not an independent predictor of cardiac events after 1 year of follow-up. CONCLUSION The prevalence of diabetes in patients who underwent PCI was very high (45%), 35% of which was patients with newly detected diabetes. In our series newly detected diabetes was not an independent predictor of outcome at 12 months. Nevertheless, this finding requires independent confirmation in other series to draw general conclusions on the whole spectrum of percutaneous interventions.

Comparación de los stents liberadores de fármaco y los convencionales en puentes de safena. Resultados inmediatos y a largo plazo

ntroduccion y objetivos. Los stents farmacoactivos (SLF) consiguen reducir la reestenosis en vasos nativos. Sin embargo, los resultados en safenas son mas confusos. Se comparan los resultados de dichos dispositivos con los de los stents convencionales (SC) en estenosis de novo. Metodos. Se estudiaron las intervenciones en safenas con SLF en cinco centros desde el inicio de su uso hasta julio de 2007 y se compararon con una cohorte historica de SC en dos de los centros. Se analizan los resultados intrahospitalarios y a largo plazo y predictores de supervivencia y revascularizacion. Resultados. Se incluyo a 98 pacientes y 107 estenosis con SLF y 113 pacientes y 130 estenosis con SC. Habia diferencias basales, con mayor edad y menor frecuencia de trombo en los SLF. Tambien se encontraron diferencias en el procedimiento con mayor longitud de stent y menos implante directo y diametro de stent en SLF. La ausencia de mortalidad cardiaca a los 12, 24 y 30 meses fue: SLF, 95% ± 2%, 91% ± 3% y 89% ± 3%; SC, 95% ± 2%, 90% ± 3% y 87% ± 3% (p = 0,66), y la ausencia de revascularizacion del vaso tratado: 90% ± 3%, 86% ± 4% y 83% ± 4% en SLF y 94% ± 2%, 87% ± 3% y 87% ± 3% en SC (p = 0,49). El unico predictor de mortalidad cardiaca fue la fraccion de eyeccion y no se encontraron predictores de nueva revascularizacion. Conclusiones. En nuestra serie los SLF en safenas no se asociaron a disminucion de mortalidad ni revascularizacion del vaso tratado. El unico predictor de mortalidad cardiaca fue la fraccion de eyeccion, y no se encontraron predictores de nueva revascularizacion

Intracoronary versus intravenous abciximab administration in patients with ST-elevation myocardial infarction undergoing thrombus aspiration during primary percutaneous coronary intervention—Effects on soluble CD40 ligand concentrations

INTRODUCTION CD40 ligand has been suggested to play a pathogenic role in atherogenesis and coronary artery disease progression. Clinical studies suggest that intravenous (IV) abciximab administration attenuates the acute inflammatory response associated with percutaneous coronary intervention (PCI). The anti-inflammatory effects of intracoronary (IC) versus IV administration of abciximab have not been systematically investigated. We assessed changes in soluble CD40 ligand (sCD40L) concentrations in response to IC versus IV abciximab in patients with ST-elevation myocardial infarction (STEMI) undergoing thrombus-aspirating device during primary PCI. METHODS Patients were randomized to receive IC (n=25) or IV (n=25) bolus abciximab followed in every case by a 12-h IV abciximab infusion. sCD40L was measured immediately before the administration of abciximab (baseline) and 60min post bolus administration. RESULTS Clinical baseline and angiographic characteristics were similar in both patient groups. Similarly, there were no significant differences in baseline serum sCD40L levels in the IC group compared to IV group (116.6+/-42.13pg/mL vs 124.9+/-43.04pg/mL, P=0.49). At 60min post PCI, however, sCD40L levels decreased by 23% (P<0.001) in the IC group and by 11% (P<0.001) in the IV group. sCD40L levels 60min post PCI were significantly reduced, particularly in the IC group compared to the IV group (73.04+/-12.21pg/mL vs 99.92+/-25.89pg/mL, P<0.001). CONCLUSION In STEMI patients undergoing primary PCI, IC bolus administration of abciximab was associated with a larger reduction in sCD40L levels compared to standard IV bolus. Whether this more powerful anti-inflammatory effect of IC abciximab translates into improved clinical outcomes deserves investigation.

The Ibero-American transcatheter aortic valve implantation registry with the CoreValve prosthesis. Early and long-term results

BACKGROUND Transcatheter aortic valve implantation (TAVI) is the recommended therapy for patients with severe aortic stenosis who are not suitable candidates for surgery. The aim of this study was to describe early experience and long-term follow-up with the CoreValve self-expanding aortic prosthesis at 42 Ibero-American hospitals. METHODS Multiple centre observational study including 1220 consecutive patients with symptomatic severe aortic stenosis who are not suitable candidates for surgery and underwent transcatheter aortic valve implantation with the self-expanding Medtronic CoreValve System between December 2007 and May 2012. RESULTS The registry included 1220 consecutive patients with a mean age of 80.8 ± 6.3 years and a mean logistic euroSCORE of 17.8% ± 13%. The procedural success rate was 96.1%. Hospital mortality was 7.3% and combined end-point was 21.3%. Aortic regurgitation after TAVI was present in 24.5% (Sellers grade ≥ 2). The estimated 1-year and 2-year survival rates were 82.1% and 73.4% respectively. The following issues were significant independent risk factors for hospital mortality: acute kidney failure (odds ratio 3.55); stroke (odds ratio 5.72); major bleeding (odds ratio 2.64) and euroSCORE (odds ratio 1.02). Long-term predictors of mortality were diabetes mellitus (hazard ratio 1.59, 95% confidence interval 1.09-2.31), severe chronic obstructive pulmonary disease (hazard ratio 1.85, 95% confidence interval 1.85-2.88), and functional classes NYHA III-IV (hazard ratio 1.31, 95% confidence interval 1.01-1.70). CONCLUSIONS Transcatheter aortic valve implantation constitutes a safe and viable therapeutic option for high operative risk patients with severe aortic stenosis. Long-term prognosis is conditioned by associate comorbidities.