Long-term clinical outcomes of coronary artery bypass graft surgery compared to those of percutaneous coronary intervention with second generation drug eluting stents in patients with stable angina and an isolated lesion in the proximal left anterior descending artery.

OBJECTIVES: We compared the long-term outcomes of percutaneous coronary intervention with second-generation drug-eluting stents (PCI-DES) and coronary artery bypass graft surgery (CABG) with the left internal mammary artery in stable angina patients with isolated single-vessel proximal left anterior descending artery (pLAD) disease. BACKGROUND: Long-term outcomes of second-generation PCI-DES and CABG in isolated pLAD lesions have not been extensively studied. METHODS: We included 631 PCI-DES patients and 379 CABG patients. Unadjusted and adjusted hazard ratios (HRs) were derived for major adverse cardiac events (MACEs), their components (cardiac death, nonfatal myocardial infarction [MI] not attributed to a non-target vessel, target-lesion revascularization), and patient-related outcome (PRO, composed of all-cause mortality, any MI, any revascularization). RESULTS: In the unadjusted and adjusted analyses, no significant difference was observed between the two groups at follow-up (mean:4.6 ± 2.5 years) for MACEs (HR: 1.45, 95% CI: 0.92-2.28, p = .11; HR:1.43, 95% CI: 0.91-2.26, p = .13), PRO (HR: 1.18, 95%CI: 0.86-1.61, p = .30; HR: 1.18, 95% CI: 0.86-1.62, p = .31), cardiac death (HR: 0.97, 95% CI: 0.46-2.05, p = .93; HR: 0.79, 95% CI: 0.36-1.72, p = .56) and MI (HR: 1.43, 95% CI: 0.49-4.13, p = .51; HR: 1.57, 95% CI: 0.53-4.64, p = .42). Compared with CABG, PCI-DES had a borderline significantly greater risk of repeat revascularization (HR: 1.99, 95% CI: 1.00-3.94, p = .05; HR: 1.95, 95% CI: 0.98-3.9, p = .06). Angina recurred more often after PCI (p < .001), whereas more arrhythmias developed after CABG (p = .02). PCI-DES resulted in fewer in-hospital complications (p < .001) and shorter hospitalizations (p < .001). CONCLUSIONS: The long-term clinical outcomes of second-generation PCI-DES and CABG in patients with stable angina and isolated pLAD disease were comparable.

Cardiac Masses: The Role of Cardiovascular Imaging in the Differential Diagnosis.

Cardiac masses are space occupying lesions within the cardiac cavities or adjacent to the pericardium. They include frequently diagnosed clinical entities such as clots and vegetations, common benign tumors such as myxomas and papillary fibroelastomas and uncommon benign or malignant primary or metastatic tumors. Given their diversity, there are no guidelines or consensus statements regarding the best diagnostic or therapeutic approach. In the past, diagnosis used to be made by the histological specimens after surgery or during the post-mortem examination. Nevertheless, evolution and increased availability of cardiovascular imaging modalities has enabled better characterization of the masses and the surrounding tissue. Transthoracic echocardiography using contrast agents can evaluate the location, the morphology and the perfusion of the mass as well as its hemodynamic effect. Transesophageal echocardiography has increased spatial and temporal resolution; hence it is superior in depicting small highly mobile masses. Cardiac magnetic resonance and cardiac computed tomography are complementary providing tissue characterization. The scope of this review is to present the role of cardiovascular imaging in the differential diagnosis of cardiac masses and to propose a step-wise diagnostic algorithm, taking into account the epidemiology and clinical presentation of the cardiac masses, as well as the availability and the incremental value of each imaging modality.

Biomarkers Associated with Bleeding Risk in the Setting of Atrial Fibrillation.

BACKGROUND: Prevention of thromboembolic disease, mainly stroke, with oral anticoagulants remains a major therapeutic goal in patients with atrial fibrillation. Unfortunately, despite the high efficacy, anticoagulant therapy is associated with a significant risk of, frequently catastrophic, and hemorrhagic complications. Among different clinical and laboratory parameters related to an increased risk of bleeding, several biological markers have been recognized and various risk scores for bleeding have been developed. OBJECTIVES/METHODS: The aim of the present study is to review current evidence regarding the different biomarkers associated with raised bleeding risk in atrial fibrillation. RESULTS: Data originating from large cohorts or the recent large-scale trials of atrial fibrillation have linked numerous individual biomarkers to an increased bleeding risk. Such a relation was revealed for markers of cardiac physiology, such as troponin, BNP and NT-proBNP, markers of renal function, such as GFR and Cystatin or hepatic function, markers involving the system of coagulation, such as D-dimer and Von Willebrand factor, hematologic markers, such as low haemoglobin or low platelets, inflammatory markers, such as interleukin-6, other factors such as GDF-15 and vitamin-E and finally genetic polymorphisms. Many such biomarkers are incorporated in the bleeding risk schemata developed for the prediction of the hemorrhagic risk. CONCLUSIONS: Biomarkers were introduced in clinical practice in order to better estimate the potential risk of haemorrhage in these patients and increase the prognostic impact of clinical risk scores. In the last years this concept is gaining significant importance.

Inhibition of Aortic Valve Calcification by Local Delivery of Zoledronic Acid-an Experimental Study.

The aim of this study was to evaluate in an experimental model of aortic valve (AV) stenosis the effectiveness of zoledronate on the inhibition of calcification. Sixteen New Zealand rabbits were placed on vitamin D-enriched diet for 3 weeks. All animals underwent PET/CT at baseline and before euthanasia to assess calcification. Thereafter, the AVs of eight animals were treated with local delivery of 500 µg/l zoledronate. A placebo mixture was administered in the remaining eight animals. Standardized uptake values were corrected for blood pool activity, providing mean tissue to background ratios (TBRmean). In the zoledronate group, there was no progression of AV calcification (TBRmean 1.20 ± 0.12 vs 1.17 ± 0.78,p = 0.29), while AV calcification progressed in the placebo group (1.22 ± 0.15 vs 1.53 ± 0.23,p = 0.006). Ascending aorta (AA) calcification progressed in both zoledronate and placebo groups. Histology confirmed the results of the PET/CT. Inhibition of AV calcification by local delivery of zoledronate is feasible and effective.

The requirement of extracorporeal circulation system for transluminal aortic valve replacement: Do we really need it in the catheterization laboratory?

Transcatheter aortic valve replacement (TAVR) is the mainstay for treating high-risk patients with aortic stenosis. As the TAVR procedures worldwide keep increasing, it is inevitable that more issues and complications will arise. Such a complication that merits attention is the conversion of TAVR into open-heart surgery and the necessity this complication creates to have an extracorporeal circulation system in the catheterization laboratory. This review contains an analysis of all major randomized trials and registries on the number and cause of TAVR procedures that ended up in open-heart surgery and presents data to challenge the prerequisite of extracorporeal circulation system in the cath laboratory. © 2015 Wiley Periodicals, Inc.

The -174 G>C Interleukin-6 Gene Polymorphism is Associated with Angiographic Progression of Coronary Artery Disease over a 4-Year Period.

BACKGROUND: Inflammation is a key process underlying the clinical course of coronary artery disease (CAD). C-reactive protein (CRP) and interleukin-6 (IL-6) contribute to its pathophysiology and act as biomarkers. We sought to examine whether known single nucleotide polymorphisms (SNPs) impact CAD progression, reflecting increased inflammation. METHODS: We retrospectively evaluated coronary angiographies of patients with established CAD who were re-investigated for stable/unstable angina after a time interval of >12 months. We defined progression of CAD as the emergence of a new plaque or a ≥20 % increase of a formerly non-significant lesion. We genotyped patients for the 1846 C>T CRP and -174 G>C IL-6 SNPs. The probability of CAD progression among the Mendelian randomization groups was evaluated using the Kaplan-Meier method. Data were analyzed using a Cox model that included relevant clinical factors. RESULTS: A total of 157 patients were included. The serum levels of CRP and IL-6 differed significantly between genotypes. The genotype frequencies of IL-6 were consistent with Hardy-Weinberg equilibrium, whereas those for CRP were excluded from our conclusions. At 48 months, 83 patients (52.9 %) with the IL-6 C allele versus 74 (47.1 %) with the G allele exhibited CAD progression. Patients with the IL-6 C allele had a 52.8 % probability for progression versus 13.3 % for those with the G allele (p=0.005). The results were confirmed by multivariate analysis; dyslipidemia, family history, and IL-6 SNP emerged as significant factors. CONCLUSION: Patients with established CAD who carried the -174 C allele of the IL-6 gene demonstrated an increased risk for the progression of coronary plaques over a four-year period. Further studies will be needed to validate these findings.

Bilateral symmetry of local inflammatory activation in human carotid atherosclerotic plaques.

INTRODUCTION: Only a few studies have investigated the structural and functional characteristics of carotid arteries bilaterally. Furthermore, there is controversy as to whether inflammation in paired vascular beds is a local or systemic phenomenon. We aimed to examine, in patients with coronary artery disease, whether intra-subject left and right carotid arteries have similar inflammatory status, as determined non-invasively by microwave radiometry (MWR). METHODS: Consecutive patients (n=200) with significant coronary artery disease were evaluated via an ultrasound echo-colour Doppler (US-ECD) study of both carotid arteries and temperature measurements with MWR. During thermography, thermal heterogeneity (ΔT) was defined as the maximum temperature along the carotid artery minus the minimum temperature. RESULTS: Mean T was similar between the left and right carotid arteries (0.78 ± 0.48 vs. 0.84 ± 0.52°C, p=0.12). Mean right intima-media thickness (IMT) was greater compared to mean left IMT (2.16 ± 1.20 vs. 1.93 ± 0.94 mm, p<0.01). In all carotids, there was a correlation between left and right carotid plaque ΔT (R=0.38, p<0.001) and between left and right IMT (R=0.48, p<0.001). Independent predictors for the presence of bilateral carotid plaques were found to be the extent of coronary artery disease, high ΔT, and therapy with angiotensin II receptor blockers; predictors for the presence of high ΔT bilaterally were bilateral carotid plaques, male sex, diabetes mellitus, and hypertension. CONCLUSIONS: There is bilateral inflammatory activation in the carotid atherosclerotic lesions of patients with coronary artery disease. At this stage of carotid disease, arterial hypertension and diabetes mellitus are more strongly correlated with bilateral functional abnormalities in carotid plaques than with structural changes.

Chemical denervation of the renal artery with vincristine for the treatment of resistant arterial hypertension: first-in-man application.

Renal artery denervation has recently emerged as a novel therapy for patients with resistant hypertension. Clinical results from renal sympathetic denervation support the safety and efficacy of this method over a period of 18 months. However, several limitations have been reported. Previous studies have shown that chemical denervation by vincristine is safe and effective in an experimental model. We describe the first-in-man application of chemical denervation with vincristine in a 74-year-old male patient with resistant arterial hypertension.

First in vivo application of microwave radiometry in human carotids: a new noninvasive method for detection of local inflammatory activation.

OBJECTIVES: This study investigated whether temperature differences: 1) can be measured in vivo noninvasively by microwave radiometry (MR); and 2) are associated with ultrasound and histological findings. BACKGROUND: Studies of human carotid artery samples showed increased heat production. MR allows in vivo noninvasive measurement of internal temperature of tissues. METHODS: Thirty-four patients undergoing carotid endarterectomy underwent screening of carotid atherosclerosis by ultrasound and MR. Healthy volunteers were enrolled as a control group. During ultrasound study, plaque texture, plaque surface, and plaque echogenicity were analyzed. Temperature difference (ΔT) was assigned as maximal minus minimum temperature. Association of thermographic with ultrasound and histological findings was performed. RESULTS: ΔT was higher in atherosclerotic carotid arteries compared with the carotid arteries of controls (p < 0.01). Fatty plaques had higher ΔT compared with mixed and calcified (p < 0.01) plaques. Plaques with ulcerated surface had higher ΔT compared with plaques with irregular and regular surface (p < 0.01). Heterogeneous plaques had higher ΔT compared with homogenous (p < 0.01). Specimens with thin fibrous cap and intense expression of CD3, CD68, and vascular endothelial growth factor (VEGF) had higher ΔT compared with specimens with thick cap and low expression of CD3, CD68, and VEGF (p < 0.01). CONCLUSIONS: MR provides in vivo noninvasive temperature measurements of carotid plaques, reflecting plaque inflammatory activation.

Oxidative stress and endothelial function: therapeutic interventions.

Cardiovascular risk factors, such as hypertension, hypercholesterolemia, diabetes mellitus, or chronic smoking, stimulate the production of reactive oxygen species (ROS) in the vascular wall. Oxidative stress and endothelial dysfunction in the coronary and peripheral circulation have important prognostic implications for subsequent cardiovascular events. The pathophysiologic causes of oxidative stress are likely to involve changes in a number of different enzyme systems. Reactive oxygen species (ROS) are produced by various oxidase enzymes, including nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, xanthine oxidase, uncoupled endothelial NO synthase (eNOS), cyclooxygenase, glucose oxidase, and lipooxygenase, and mitochondrial electron transport. Decreased NO production due to changes in the expression and activity of eNOS and increased degradation of NO, by reaction with superoxide account for the reduction in endothelium-dependent vascular relaxation. Recently, a variety of antioxidants have been extensively studied in clinical trials for the prevention and treatment of atherosclerosis. In small clinical studies both vitamins C and E may improve endothelial function in high-risk patients. However, larger interventional trials have been controversial, suggesting potential harm in certain high-risk populations. Antihypertensive and hypolipidemic medications exhibit well-documented antioxidant effects and improve endothelial function. However, the discussion of recent patents with the novel antioxidant strategies are required to clarify the role of antioxidant intervention in vascular diseases.

Avastin-eluting stent: long-term angiographic and clinical follow up.

The detection of atheromatous lesions in patients with coronary artery disease is related to neovascularisation, since it is associated with the presence of a dense network of vasa vasorum in the vascular wall. The increased density of vasa vasorum causes destabilisation of the atheromatous plaque. The safety and efficacy of a stent coated with bevacizumab, a monoclonal antibody for vascular endothelial growth factor have been established at both the experimental and the clinical level. We present the case of a patient with acute myocardial infarction and significant stenosis in the mid-section of the left anterior descending coronary artery, treated by implantation of a bevacizumab-coated stent. A coronary angiographic examination 2 years later showed patent coronary arteries with a well-preserved angioplasty result in the anterior descending artery. This is the first report of findings beyond six-month follow up of this type of stent and represents the first clinical and angiographic proof of its long-term efficacy.

A preliminary experience report: Drug-eluting stents versus coronary artery bypass surgery in patients with a single lesion in the proximal left anterior descending artery suffering from diabetes mellitus and chronic stable angina.

INTRODUCTION: Treatment of lesions located in the proximal segment of the left anterior descending artery (pLAD), either with coronary artery bypass grafting (CABG) or percutaneous coronary intervention, in patients with diabetes mellitus has been associated with an unfavourable outcome. The aim of the present study was to compare the long-term clinical outcome of drug-eluting stents (DES) vs. CABG with a left internal mammary artery (LIMA) graft in patients with a pLAD lesion who suffered from chronic stable angina and diabetes mellitus. METHODS: We studied 77 consecutive patients suffering from chronic stable angina, diabetes mellitus, and with an isolated pLAD lesion. Thirty-nine patients underwent DES implantation and 38 LIMA grafting. Primary endpoints were the occurrence of major adverse cardiac events, defined as death, myocardial infarction, and target vessel revascularisation. Secondary endpoints included the length of stay in hospital, in-hospital complications, and the recurrence of chest pain. RESULTS: More in-hospital complications were observed in the CABG group than in the DES group. The mean duration of hospitalisation after CABG was 7.76 +/- 2.82 days vs. 1.17 +/- 1.15 days after DES. The mean follow-up period was 19.7 +/- 6.3 months for the DES group and 19.7 +/- 7.4 months for the surgical group. The incidence of major adverse cardiac events was similar in the two groups. There were two re-interventions in the DES group and none in the surgical group. Recurrent angina occurred in 2 patients in the DES group and 3 patients in the CABG group. CONCLUSIONS: The present study demonstrates that patients with diabetes mellitus, chronic stable angina, and single vessel disease in the pLAD have an excellent long-term outcome with both DES implantation and LIMA anastomosis. The surgical approach, however, was associated with more in-hospital complications and a longer hospitalisation.

Drug eluting stents versus coronary artery bypass surgery in patients with isolated proximal lesion in left anterior descending artery suffering from chronic stable angina.

OBJECTIVE: To compare the efficacy of drug eluting stents (DES) compared with bypass surgery (CABG) with left internal mammary artery (LIMA) in patients with single vessel disease suffering from chronic stable angina. BACKGROUND: There are a limited number of studies investigating this group of patients. METHODS: We included 257 consecutive patients with isolated lesion in the proximal segment of left anterior descending artery (LAD). All patients suffered from chronic stable angina or from stress-induced ischemia. Of 257 patients, 147 underwent DES implantation and 110 CABG with LIMA. All patients were followed-up clinically for major adverse cardiac events. RESULTS: The baseline demographic and angiographic characteristics were similar between the two groups. In the DES group we used sirolimus-, paclitaxel-, and ABT-578-eluting stents. The mean duration of hospitalization after CABG was 7.86 +/- 3.84 days vs. 1.02 +/- 0.19 days after PCI (P < 0.01). The incidence of MACE was 2.72% in the DES and 2.72% in the surgical group during a mean follow-up period of 18.71 +/- 6.27 months for PCI and 18.70 +/- 7.31 months for CABG (P = 0.99). There was one cardiac related death in the DES group and two in the surgical group (P = 0.58). There were three reinterventions in the DES group versus none in the surgical group (P = 0.26). Recurrence of angina was observed in 4.08% of pts in the DES group versus 6.36% in the CABG group (P = 0.57). CONCLUSIONS: The present study demonstrated that patients suffering from chronic stable angina with isolated lesion in the proximal segment of LAD have excellent long-term outcome in both surgical and DES treatment.