Atrioventricular dissociation due to pheochromocytoma in a young adult.

Atrioventricular dissociation can be a manifestation of an underlying noncardiac disease.We present a patient who underwent pacemaker implantation because of intermittent atrioventricular dissociation and medically untreatable supraventricular arrhythmias, which could not be induced by electrophysiological testing. The arrhythmias proved to be due to a pheochromocytoma. After left adrenalectomy, both the supraventricular arrhythmias and the atrioventricular dissociation disappeared. Adequate recognition and treatment of pheochromocytoma can reverse atrioventricular dissociation and may avoid unnecessary procedures such as electrophysiological testing and pacemaker implantation.

Effects of cytochalasin D-eluting stents on intimal hyperplasia in a porcine coronary artery model.

OBJECTIVE: To investigate whether cytochalasin D-eluting stents (CDES) suppress intimal hyperplasia in porcine coronary arteries and to compare the efficacy of paclitaxel and cytochalasin D as inhibitors of vascular smooth muscle cell (SMC) proliferation and platelet aggregation in vitro. METHODS: Rabbit platelet-rich plasma and SMC cultures derived from rabbit aortas were exposed to 10(-8)-10(-5) M cytochalasin D or paclitaxel. Stents directly coated with 2 microg cytochalasin D (low-dose CDES, n=12) and bare stents (n=12) were randomly deployed in the right and left coronary artery of 12 pigs. Six weeks later, neointima was studied using quantitative coronary angiography (QCA) and morphometry. To examine a ten-fold higher dose, polybutyl methacrylate/polyvinyl acetate-coated stents were loaded with 20 microg cytochalasin D. High-dose CDES (n=10) and polymer-only stents (n=11) were deployed in 11 pigs. RESULTS: After 7 days, cytochalasin D (IC(50) 9.9+/-0.4 10(-8) M) and paclitaxel (IC(50) 1.1+/-0.4 10(-8) M) inhibited SMC proliferation in vitro (n=4). In contrast, cytochalasin D (10(-6)-10(-5) M, n=5), but not paclitaxel, attenuated platelet shape change and aggregation induced by ADP. In vivo QCA showed less late lumen loss in low-dose CDES (0.08+/-0.07 vs. 0.32+/-0.08 mm, P=0.05), but morphometry demonstrated only a tendency toward a decreased intimal area. High-dose CDES inhibited both late lumen loss (0.31+/-0.08 vs. 0.91+/-0.06 mm, P<0.01) and intimal area (1.57+/-0.20 vs. 2.46+/-0.22 mm(2), P<0.01). Immunohistochemistry revealed that CDES suppressed peri-strut macrophage recruitment (CD68, P=0.04) and cell proliferation (Ki67, P=0.03) as compared to polymer-only stents without interfering with endothelial cell recovery or the density of alpha-SMC actin staining. Thromboses or edge effects were not observed in either study. CONCLUSIONS: CDES inhibited in-stent hyperplasia. The reduction (39%) with 20 mug CDES was equivalent to that reported for paclitaxel-eluting stents in pigs. Interference with platelet aggregation, SMC migration, SMC proliferation, and leukocyte recruitment could contribute to the benefit. The data indicate that targeting of actin microfilaments has a potential to suppress in-stent restenosis.

Systemic inflammation and reperfusion injury in patients with acute myocardial infarction.

Despite early recanalization of an occluded infarct artery, tissue reperfusion remains impaired in more than one-third of the acute myocardial infarction (AMI) patients owing to a process of reperfusion injury. The role of systemic inflammation in triggering this phenomenon is unknown. Proinflammatory factors (hs-CRP, TNF-alpha ) and anti-inflammatory mediators (IL-1 receptor antagonist, IL-10) were measured in 65 patients during the acute phase of a myocardial infarction as well as in 11 healthy control subjects. Myocardial reperfusion injury was defined as the presence of persistent ST-segment elevation despite successful coronary intervention (> or = 50 of the initial value) and was observed in 28 patients. Systemic proinflammatory mediators (particularly hs-CRP and leukocytes) were higher in AMI patients compared to control subjects. Within the group of AMI patients, only serum TNF-alpha differed significantly between patients with versus without reperfusion injury: a median value of 25 versus 13 pg/mL was observed, respectively. Logistic regression analysis identified a high level of TNF-alpha as the most important independent determinant of reperfusion injury (P = .001), beyond total ischemic time (P = .01) and extent of jeopardized myocardium (P = .08). There was no correlation between the TNF-alpha level and the total ischemic time (P = .8) or the extent of jeopardized myocardium (P = .6). Systemic inflammation, in particular high levels of TNF-alpha , is strongly associated with the occurrence of reperfusion injury after successful recanalization. Our findings suggest that TNF-alpha is involved in the triggering and/or amplification of local inflammatory responses related to ischemia-reperfusion injury.

Does pre-treatment with aspirin and loading dose clopidogrel obviate the need for glycoprotein IIb/IIIa antagonists during elective coronary stenting? A focus on peri-procedural myonecrosis.

AIMS: Although full platelet inhibition with aspirin and thienopyridines before coronary stenting has significantly reduced the risk of acute stent thrombosis, peri-procedural myonecrosis still occurs frequently and is associated with increased death rate. Whether further inhibition of platelet aggregation by a glycoprotein IIb/IIIa antagonist may provide an additional cardioprotection is unknown. METHODS AND RESULTS: A total of 200 patients pre-treated with aspirin and a loading dose of clopidogrel (450 mg) were randomized just before coronary intervention (percutaneous coronary intervention, PCI) to treatment with or without abciximab. Platelet aggregation was assessed in samples collected during the procedure and the degree of platelet aggregation inhibition was correlated with cardiac enzyme release post-PCI. Abciximab treatment achieved a more complete inhibition of aggregation than dual oral antiplatelet therapy alone (median value of 1 vs. 50%, normal 100%). Any pathological increase in creatinine kinase-MB (CK-MB) post-PCI was present in 21% of the abciximab group and in 22% of the no-abciximab group (P = 0.9). Also the occurrence of clinically relevant myonecrosis [myocardial infarction (MI) = CK-MB > 3x upper limit of normal] was not significantly influenced by treatment assignment: 9 vs. 10% (P = 0.9). In a multiple logistic regression model including clinical, angiographic, and procedural characteristics, post-PCI myonecrosis was not correlated with the degree of platelet aggregation inhibition but with procedural features (such as long inflation time) and with the presence of multi-vessel disease. There were no cases of acute or subacute stent thrombosis. At 6 months, major adverse cardiac events, including cardiac death, non-fatal MI, or target lesion revascularization occurred in 13% of abciximab patients and in 16% of the control patients (P = 0.6). CONCLUSIONS: In the studied patients scheduled for elective coronary stenting and pre-treated with aspirin and a loading dose of clopidogrel, further inhibition of platelet aggregation by abciximab does not afford additional cardioprotection. Our data suggest that distal athero-embolization rather than thrombo-embolization is involved in the phenomenon of myonecrosis post-elective stenting.

Effect of intracoronary adenosine infusion during coronary intervention on myocardial reperfusion injury in patients with acute myocardial infarction.

Despite early recanalization of an occluded infarct artery, up to 33% of patients with acute myocardial infarction do not obtain complete myocardial reperfusion due to a process of reperfusion injury. This study assessed whether adjunctive therapy with adenosine might prevent or attenuate the phenomenon of myocardial reperfusion injury. Myocardial reperfusion was assessed in 79 consecutive patients receiving a 20-minute intracoronary infusion of adenosine during percutaneous coronary intervention (PCI) and in a historical cohort of 200 patients with acute myocardial infarction who were treated with PCI (controls). Myocardial reperfusion injury was defined as persistent (> or =50% of initial value) ST-segment elevation after successful recanalization. Its effect on infarct size was evaluated by calculating the Selvester QRS score before intervention and at follow-up. Myocardial reperfusion injury was present in 19% of patients receiving adenosine versus 35% of control patients (p = 0.004). Evaluation of infarct expansion over time showed almost no change in the QRS score in patients receiving adenosine (3.4 +/- 3.0 before PCI; 3.5 +/- 3.1 at follow-up). In contrast, infarct QRS score in the control group worsened from 3.1 +/- 2.7 before PCI to 4.5 +/- 3.2 at follow-up (p = 0.003 treatment with adenosine vs control). Multivariate analysis identified adjunctive therapy with adenosine as an independent protective determinant of myocardial reperfusion injury and of infarct expansion. The rate of major adverse cardiac events (death and myocardial infarction) at 1 month tended to be lower in patients receiving adenosine (4% vs 6.5%, p = 0.7) and was mainly observed in patients with evidence of myocardial reperfusion injury (cardiac event rate 2% in patients with ST-segment elevation of <50% vs 14% in patients with ST-segment elevation > or =50%, p = 0.003). Thus, impaired myocardial reperfusion is the most important determinant of clinical outcome in patients with acute myocardial infarction treated with PCI. Adjunctive therapy with intracoronary infusion of adenosine during PCI prevents the occurrence of severe myocardial reperfusion injury and is associated with less infarct expansion.

Long (> or = 25 mm) stents for long coronary artery lesions. A safe conduct or a bridge too far for the interventional cardiologist?

OBJECTIVE: Increased restenosis rates have been reported after stenting long lesions with multiple standard length stents. Long slotted tube stents have become available for the treatment of long lesions or dissections. To compare clinical outcome after the use of long Multi-Link stents in long coronary lesions versus standard length Multi-Link stents in Benestent type lesions. METHODS AND RESULTS: We evaluated clinical outcome (six months) of 147 consecutive patients in whom one or more > or = 25 mm long Multi-Link stents were successfully deployed. The results were compared with the West-2 registry in which a 15 mm Multi-Link stent was used. The patients with long stents had more complex lesions and unstable symptoms. Target lesion revascularization after six months follow-up was comparable with that observed after implantation of a standard length stent (6.9% vs. 6.1%, p = 0.81). Overall cardiac event-free survival was similar for both groups (89.7% vs. 91.5%, p = 0.73). CONCLUSIONS: Patients treated with one or more long (> or = 25 mm) Multi-Link stents have a similar event-free survival and an equivalent target lesion repeat revascularization risk after six months than patients treated with a standard length stent.

Addition of cytochalasin D to a biocompatible oil stent coating inhibits intimal hyperplasia in a porcine coronary model.

BACKGROUND: Polymer-based, drug-eluting stents, are currently under extensive investigation in the conquest against in-stent restenosis. Concern remains, however, about potential long-term lack of biocompatibility of the polymers used in these studies. Therefore, this study aimed to evaluate in porcine coronary arteries (1) the in vivo biocompatibility of a new natural, eicosapentaenoic acid oil stent-coating and (2) the efficacy of this coating in preventing in-stent restenosis when cytochalasin D--an inhibitor of actin filament formation, that interferes with cell proliferation and migration--was added. METHODS AND RESULTS: To assess in vivo biocompatibility of the oil coating, 15 bare and 15 oil-coated stents were randomly deployed in coronary arteries of 15 pigs. No difference in tissue response, regarding inflammation or proliferation, was seen between both groups at five days or at four weeks follow-up. To evaluate the efficacy of the coating in preventing in-stent restenosis by adding a potential anti-restenotic drug, stents were dip-coated in 20 mg cytochalasin D/ml oil solution, resulting in 93 +/- 18 microg cytochalasin D/stent load (n = 3). In vitro drug release studies showed sustained release up to four weeks. Next, 11 oil-coated and 11 cytochalasin D-loaded stents were randomly implanted in coronary arteries of 11 pigs. At four weeks, a 39% decrease in neointimal hyperplasia (p < 0.05, ANCOVA, with injury as covariate) was found in cytochalasin D-loaded stents compared to oil-coated stents. CONCLUSIONS: This new natural oil stent-coating shows excellent biocompatibility to vascular tissue. Local cytochalasin D delivery from this stent-platform significantly inhibits neointimal hyperplasia in a porcine coronary model.

A three-dimensional quantitative analysis of restenosis parameters after balloon angioplasty: comparison between semi-automatic computer-assisted planimetry and stereology.

Semi-automatic computer-assisted planimetry is often used for the quantification of restenosis parameters after balloon angioplasty although it is a time-consuming method. Moreover, slicing the artery to enable analysis of two-dimensional (2-D) images leads to a loss of information since the vessel structure is three-dimensional (3-D). Cavalieri's principle uses systematic random sampling allowing 3-D quantification. This study compares the accuracy and efficiency of planimetry versus point-counting measurements on restenosis parameters after balloon angioplasty and investigates the use of Cavalieri's principle for 3-D volume quantification. Bland and Altman plots showed good agreement between planimetry and point counting for the 2-D and 3-D quantification of lumen, internal elastic lamina (IEL) and external elastic lamina (EEL), with a slightly smaller agreement for intima and media. Mean values and induced coefficients of variation were similar for both methods for all parameters. Point counting induced a 6% error in its 3-D quantification, which is negligible in view of the biological variation (>90%) among animals. However, point counting was 3 times faster compared to planimetry, improving its efficiency. This study shows that combining Cavalieri's principle with point counting is a precise and efficient method for the 3-D quantification of restenosis parameters after balloon angioplasty.