Johan Bosmans

Determinants and Prognostic Implications of Persistent ST-Segment Elevation After Primary Angioplasty for Acute Myocardial Infarction Importance of Microvascular Reperfusion Injury on Clinical Outcome

BACKGROUND Despite early recanalization of an occluded infarct artery, reperfusion at the level of the microcirculation may remain impaired owing to a process of microvascular reperfusion injury. METHODS AND RESULTS Microvascular reperfusion injury was studied in 91 patients with acute myocardial infarction (AMI) by evaluation of the resolution of ST-segment elevation after successful PTCA. Impaired microvascular reperfusion, defined as the presence of persistent (>/=50% of initial value) ST-segment elevation (ST >/=50%) at the end of coronary intervention, was observed in 33 patients (36%) and was independently correlated with low systolic pressure on admission and high age. Patients >/=55 years of age with systolic pressures </=120 mm Hg were at high risk for development of impaired reperfusion compared with patients not meeting these criteria (72% versus 14%, P<0.001). Impaired microvascular reperfusion was associated with a more extensive infarction and worse clinical outcome at the 1-year follow-up: cardiac death rate, 15% versus 2% (ST >/=50% versus ST <50%, P=0.01); nonfatal MI rate, 9% versus 2% (P=0.1); and total major adverse cardiac event (MACE) rate, 45% versus 15% (P<0.005). ST >/=50% was the most important independent determinant of MACE with an adjusted risk ratio of 3.4. CONCLUSIONS Impaired microvascular reperfusion, as evidenced by ST >/=50% after successful recanalization, occurs in more than one third of our AMI patients, especially in older patients with low systolic pressure. Its detrimental implications on clinical outcome reinforce the need to develop adjunctive agents that attenuate the process of reperfusion injury.

Procedural, 30-day and one year outcome following CoreValve or Edwards transcatheter aortic valve implantation: results of the Belgian national registry

We report clinical outcomes following transcatheter aortic valve implantation (TAVI), using the CoreValve revalving system (18 Fr transfemoral or subclavian) or the Edwards Sapien valve (22 Fr transfemoral or 24 Fr transapical) as part of a Belgian prospective non-randomized multicentre registry. All 15 Belgian centres performing TAVI participated to this registry (seven exclusively Edwards Sapien, eight exclusively CoreValve). All consecutive high-risk symptomatic patients with severe aortic stenosis were evaluated by a heart team and screened for eligibility for TAVI. Three hundred and twenty-eight patients underwent TAVI with CoreValve (n = 141; eight subclavian and 133 transfemoral) or Edwards Sapien (n = 187; 99 transfemoral and 88 transapical) up to April 2010. Procedural success was 97%. One-month survival was 88% for the Edwards and 89% for the CoreValve treated patients. One-month mortality was both related to cardiac and non-cardiac reasons. Overall one-year survival was 78% in the CoreValve transfemoral treated patients, 100% in the CoreValve subclavian treated patients, 82% in the Edwards transfemoral treated patients and 63% in the Edwards transapical treated patients. This mid-term mortality was mainly related to age-related, non-cardiac complications.

Phagocytosis and Macrophage Activation Associated With Hemorrhagic Microvessels in Human Atherosclerosis

Objective—Previously, we demonstrated that activated inducible NO synthase (iNOS)-expressing foam cells in human carotid plaques often produce autofluorescent (per)oxidized lipids (ceroid). Here, we investigate whether intraplaque microvessels can provide foam cells with lipids and trigger macrophage activation. Methods and Results—Microvessels (von Willebrand factor [vWf] immunoreactivity), activated macrophages (iNOS immunoreactivity), and ceroid were systematically mapped in longitudinal sections of 15 human carotid endarterectomy specimens. An unbiased hierarchical cluster analysis classified vascular regions into 2 categories. One type with normal vWf expression and without inflammatory cells was seen, and another type with cuboidal endothelial cells, perivascular vWf deposits, and iNOS and ceroid-containing foam cells was seen in 4 (27%) of 15 plaques. The perivascular foam cells frequently contained platelets (glycoprotein Ib&agr;) and erythrocytes (hemoglobin, iron), pointing to microhemorrhage/thrombosis and subsequent phagocytosis. Similar lipid-containing cells, expressing both ceroid and iNOS, were generated in atherosclerosis-free settings by incubating murine J774 macrophages with platelets or oxidized erythrocytes and also in vivo in organizing thrombi in normocholesterolemic rabbits. Conclusions—Focal intraplaque microhemorrhages initiate platelet and erythrocyte phagocytosis, leading to iron deposition, macrophage activation, ceroid production, and foam cell formation. Neovascularization, besides supplying plaques with leukocytes and lipoproteins, can thus promote focal plaque expansion when microvessels become thrombotic or rupture prone.

Transcatheter Aortic Valve Implantation for Pure Severe Native Aortic Valve Regurgitation

OBJECTIVES This study sought to collect data and evaluate the anecdotal use of transcatheter aortic valve implantation (TAVI) in pure native aortic valve regurgitation (NAVR) for patients who were deemed surgically inoperable BACKGROUND Data and experience with TAVI in the treatment of patients with pure severe NAVR are limited. METHODS Data on baseline patient characteristics, device and procedure parameters, echocardiographic parameters, and outcomes up to July 2012 were collected retrospectively from 14 centers that have performed TAVI for NAVR. RESULTS A total of 43 patients underwent TAVI with the CoreValve prosthesis (Medtronic, Minneapolis, Minnesota) at 14 centers (mean age, 75.3 ± 8.8 years; 53% female; mean logistic EuroSCORE (European System for Cardiac Operative Risk Evaluation), 26.9 ± 17.9%; and mean Society of Thoracic Surgeons score, 10.2 ± 5.3%). All patients had severe NAVR on echocardiography without aortic stenosis and 17 patients (39.5%) had the degree of aortic valvular calcification documented on CT or echocardiography. Vascular access was transfemoral (n = 35), subclavian (n = 4), direct aortic (n = 3), and carotid (n = 1). Implantation of a TAVI was performed in 42 patients (97.7%), and 8 patients (18.6%) required a second valve during the index procedure for residual aortic regurgitation. In all patients requiring second valves, valvular calcification was absent (p = 0.014). Post-procedure aortic regurgitation grade I or lower was present in 34 patients (79.1%). At 30 days, the major stroke incidence was 4.7%, and the all-cause mortality rate was 9.3%. At 12 months, the all-cause mortality rate was 21.4% (6 of 28 patients). CONCLUSIONS This registry analysis demonstrates the feasibility and potential procedure difficulties when using TAVI for severe NAVR. Acceptable results may be achieved in carefully selected patients who are deemed too high risk for conventional surgery, but the possibility of requiring 2 valves and leaving residual aortic regurgitation remain important considerations.

Transcatheter aortic valve replacement in bicuspid aortic valve disease.

BACKGROUND Limited information exists describing the results of transcatheter aortic valve (TAV) replacement in patients with bicuspid aortic valve (BAV) disease (TAV-in-BAV). OBJECTIVES This study sought to evaluate clinical outcomes of a large cohort of patients undergoing TAV-in-BAV. METHODS We retrospectively collected baseline characteristics, procedural data, and clinical follow-up findings from 12 centers in Europe and Canada that had performed TAV-in-BAV. RESULTS A total of 139 patients underwent TAV-in-BAV with the balloon-expandable transcatheter heart valve (THV) (n = 48) or self-expandable THV (n = 91) systems. Patient mean age and Society of Thoracic Surgeons predicted risk of mortality scores were 78.0 ± 8.9 years and 4.9 ± 3.4%, respectively. BAV stenosis occurred in 65.5%, regurgitation in 0.7%, and mixed disease in 33.8% of patients. Incidence of type 0 BAV was 26.7%; type 1 BAV was 68.3%; and type 2 BAV was 5.0%. Multislice computed tomography (MSCT)-based TAV sizing was used in 63.5% of patients (77.1% balloon-expandable THV vs. 56.0% self-expandable THV, p = 0.02). Procedural mortality was 3.6%, with TAV embolization in 2.2% and conversion to surgery in 2.2%. The mean aortic gradient decreased from 48.7 ± 16.5 mm Hg to 11.4 ± 9.9 mm Hg (p < 0.0001). Post-implantation aortic regurgitation (AR) grade ≥ 2 occurred in 28.4% (19.6% balloon-expandable THV vs. 32.2% self-expandable THV, p = 0.11) but was prevalent in only 17.4% when MSCT-based TAV sizing was performed (16.7% balloon-expandable THV vs. 17.6% self-expandable THV, p = 0.99). MSCT sizing was associated with reduced AR on multivariate analysis (odds ratio [OR]: 0.19, 95% confidence intervals [CI]: 0.08 to 0.45; p < 0.0001). Thirty-day device safety, success, and efficacy were noted in 79.1%, 89.9%, and 84.9% of patients, respectively. One-year mortality was 17.5%. Major vascular complications were associated with increased 1-year mortality (OR: 5.66, 95% CI: 1.21 to 26.43; p = 0.03). CONCLUSIONS TAV-in-BAV is feasible with encouraging short- and intermediate-term clinical outcomes. Importantly, a high incidence of post-implantation AR is observed, which appears to be mitigated by MSCT-based TAV sizing. Given the suboptimal echocardiographic results, further study is required to evaluate long-term efficacy.

Inducible nitric oxide synthase colocalizes with signs of lipid oxidation/peroxidation in human atherosclerotic plaques

OBJECTIVE Advanced human atherosclerotic plaques are characterized by the abundant presence of the autofluorescent non-soluble lipid pigment ceroid, consisting of oxidized lipoproteins. The aim of the present study was to examine the topographical and cellular distribution of inducible nitric oxide synthase (iNOS or NOS II) within different stages of atherosclerosis and its colocalization with ceroid deposits and nitrotyrosine. METHODS AND RESULTS Different stages of atherosclerosis were studied by immunohistochemistry on whole-mount longitudinal sections of carotid endarterectomy specimens. In the adaptive intimal thickening the predominant cell type were smooth muscle cells. The fatty streaks contained both smooth muscle cells and macrophages with an extremely low NOS II immunoreactivity. The advanced atherosclerotic plaques however, showed a very dense infiltration by macrophages, of which a subpopulation expressed NOS II as a vesicular immunoreactivity in their cytoplasm. These were mainly present around the necrotic core, in association with ceroid accumulation and nitrotyrosine. Fluorescence quenching microscopy showed the presence of NOS II on autofluorescent ceroid vesicles in the macrophages. Large extracellular ceroid granules were not NOS II immunoreactive. NOS II mRNA was detected by RT-PCR and the protein by Western blot in the plaque tissue but not in mammary arteries used as controls. CONCLUSION Ceroid, nitrotyrosine and NOS II colocalized in late stages of atherosclerosis and were found around the necrotic core in the plaque. This could suggest that NOS II expression in macrophages is involved in oxidation and peroxidation of lipids, leading to ceroid formation.

Chronic heart failure: an example of a systemic chronic inflammatory disease resulting in cachexia

Chronic heart failure is no longer a mere cardiac entity, but involves several, initially adaptive and later detrimental, neurohumoral compensatory mechanisms. Peripheral manifestations of the disease, such as endothelial dysfunction, skeletal muscle changes, and disturbances in ventilatory control, are major determinants of symptoms. The independent prognostic value and the relevance of cachexia on morbidity of patients with chronic heart failure have only recently been recognised. Altered body composition in heart failure patients is reflected in the early loss of muscle tissue but affects all tissue compartments in case of cardiac cachexia. Recently, a new portfolio of biologically active molecules, termed cytokines, have been shown to play an important role in the development and progression of both cardiac and peripheral abnormalities. Similar to other chronic illnesses, covered in the remainder of this issue, a low-grade chronic inflammatory process may be of particular relevance in the development of tissue wasting in these patients. Whereas the presence of immune activation in chronic heart failure is now widely accepted, as well as the prognostic relevance of chronic inflammation, the site and the source of cytokine production remain the object of intense research. Although the inciting event is located in the heart, cross-talk between the myocardium on the one hand, and the immune system, peripheral tissues and organs on the other hand, will lead to the overproduction of proinflammatory cytokines and, inevitably, to their detrimental effects. The specific problems related to heart failure progression and inflammatory activation are described in this review.

Blood Transfusion and the Risk of Acute Kidney Injury After Transcatheter Aortic Valve Implantation

Background—Blood transfusion is associated with acute kidney injury (AKI) after transcatheter aortic valve implantation (TAVI). We sought to elucidate in more detail the relation between blood transfusion and AKI and its effects on short- and long-term mortality. Methods and Results—Nine hundred ninety-five patients with aortic stenosis underwent TAVI with the Medtronic CoreValve or the Edwards Valve in 7 centers. AKI was defined by the Valve Academic Research Consortium (absolute increase in serum creatinine ≥0.3 mg/dL [≥26.4 &mgr;mol/L] or ≥50% increase <72 hours). Logistic and Cox regression was used for predictor and survival analysis. AKI occurred in 20.7% (n=206). The number of units of blood transfusion <24 hours was the strongest predictor of AKI (≥5 units, OR, 4.81 [1.45–15.95], 3–4 units, OR, 3.05 [1.24–7.53], 1–2 units, OR, 1.47 [0.98–2.22]) followed by peripheral vascular disease (OR, 1.48 [1.05–2.10]), history of heart failure (OR, 1.43 [1.01–2.03]), leucocyte count <72 hours after TAVI (OR, 1.05 [1.02–1.09]) and European System for Cardiac Operative Risk Evaluation (EuroSCORE; OR, 1.02 [1.00–1.03]). Potential triggers of blood transfusion such as baseline anemia, bleeding-vascular complications, and perioperative blood loss were not identified as predictors. AKI and life-threatening bleeding were independent predictors of 30-day mortality (OR, 3.15 [1.56–6.38], OR, 6.65 [2.28–19.44], respectively), whereas transfusion (≥3 units), baseline anemia, and AKI predicted mortality beyond 30 days. Conclusions—AKI occurred in 21% of the patients after TAVI. The number of blood transfusions but not the indication of transfusion predicted AKI. AKI was a predictor of both short- and long-term mortality, whereas blood transfusion predicted long-term mortality. These findings indicate that outcome of TAVI may be improved by more restrictive use of blood transfusions.

Coronary Flow Reserve During Coronary Angioplasty in Patients With a Recent Myocardial Infarction: Relation to Stenosis and Myocardial Viability

OBJECTIVES In the present study, we examined post-stenotic coronary flow before and after percutaneous transluminal coronary angioplasty (PTCA) in patients with and without a recent myocardial infarction (MI) and related it to stenosis severity and residual viability. BACKGROUND Post-stenotic coronary blood flow velocity reserve (CFVR) has been used with success to estimate functional stenosis severity in patients with stable angina. However, in patients with a recent MI, the impaired coronary vasodilator response of the reperfused myocardium may substantially alter the flow dynamics of the infarct-related artery. METHODS Distal coronary flow velocities were recorded before and after PTCA in 36 patients at day 13 +/- 7 (mean +/- SD) after acute MI and in 38 patients without MI. The CFVR was assessed by the ratio of distal hyperemic to baseline average peak velocity, using a 0.014-in. Doppler guide wire. Stenosis severity was analyzed by quantitative coronary angiography, and infarct size was assessed scintigraphically. RESULTS For similar angiographic stenosis severity, pre- and post-PTCA values of CFVR were significantly lower in patients with than without MI: 1.22 +/- 0.26 versus 1.50 +/- 0.45 before PTCA (p < 0.05) and 1.72 +/- 0.43 versus 2.21 +/- 0.74 after PTCA, respectively (p < 0.01). Although CFVR increased significantly (p < 0.0001) after angiographically successful PTCA in both study groups, abnormal CFVR (< or = 2.0) was still observed in 80% of patients with MI and in 44% of those without MI (MI vs. no MI, p = 0.001). Patients with an extensive infarction (relative infarct size > or = 50%) and those with a small infarction (relative infarct size < 50%) had comparable levels of post-PTCA CFVR (1.6 +/- 0.3 vs. 1.8 +/- 0.5, p = NS). Among a variety of factors, angiographic stenosis severity was the most important determinant of CFVR in both study groups. CONCLUSIONS In patients with a recent MI, CFVR was significantly lower than in those without MI, both before and after PTCA. Besides the presence of this postreperfusion-related impairment of the coronary vasodilating response, CFVR was mainly influenced by stenosis severity and not by residual viability.

Decreased number of circulating plasmacytoid dendritic cells in patients with atherosclerotic coronary artery disease

Background Dendritic cells are potent antigen-presenting and immune modulating cells that have been implicated in the development of atherosclerosis. In human blood, two distinct lineages are distinguished: plasmacytoid dendritic cells and myeloid dendritic cells. Although dendritic cells have been described in atherosclerotic plaques, no information exists concerning circulating blood dendritic cells in atherosclerosis. This study aims to evaluate the number of circulating dendritic cells in patients with coronary artery disease. The relation with the extent of coronary artery disease, the clinical syndrome and with a marker of inflammation will be documented. Methods Patients with angiographically proven coronary artery disease (n=18) and age and sex-matched controls (n=18) were included. Myeloid dendritic cells and plasmacytoid dendritic cells were detected with the specific blood dendritic cell antigens, blood dendritic cell antigen-1 and blood dendritic cell antigen-2, respectively. Results Absolute and relative numbers of circulating plasmacytoid dendritic cells were significantly lower in patients with coronary artery disease (5722±601/ml and 0.08±0.01%) than in controls (12640±1289/ml and 0.21±0.02%). Plasmacytoid dendritic cells were more decreased in patients with troponin-positive unstable coronary syndromes than in patients with low troponin values, and tended to be lower in more extensive coronary artery disease. Absolute myeloid dendritic cells numbers tended to be reduced in patients, whereas relative numbers were significantly decreased: 11 857±1895/ml versus 15 226±928/ml and 0.17±0.03% versus 0.26±0.01% in controls. Conclusions The present study shows a significant decrease of circulating blood dendritic cell antigen-2 positive plasmacytoid dendritic cells in patients with coronary artery disease. The decrease tended to be more pronounced in unstable coronary syndromes and extensive coronary artery disease, suggesting a possible role of dendritic cells in plaque progression and rupture.