Pseudoaneurysm Formation After "Preclose"-Assisted Impella Insertion in a Patient With Cardiogenic Shock.

The use of mechanical support devices such as the Impella CP (Abiomed, Danvers, MA) is a growing form of treatment for patients with cardiogenic shock (CS). Despite the increase in usage, there remains a dearth in literature regarding potential complications. Vascular complications such as pseudoaneurysms (PAs) are rare but important potential complications that can occur with use of the Impella. We present Impella-assisted percutaneous coronary intervention (PCI) in a patient with CS, "Preclosed" with the Perclose ProGlide (Abbott, Plymouth, MN) device complicated by development of a PA. A 62-year-old male patient with a history of diabetes and hypertension presented to our emergency room (ER) with chest pain and electrocardiogram (ECG) findings consistent with an acute anterior wall ST-elevation myocardial infarction (STEMI). This was further complicated by refractory CS. The patient was urgently taken to the cardiac catherization laboratory. After exchange of sequential dilators, a single Perclose device was used prior to the insertion of the Impella sheath. The patient then underwent a successful Impella-assisted PCI of his left anterior descending artery. Upon stabilization of hemodynamics, the patient was taken to the catheterization laboratory for Impella removal. After removal of Impella, imaging detected extravasation of contrast, without development of hematoma, later confirmed to be a PA via computed tomography (CT) scans and ultrasound Doppler imaging. The PA was successfully managed with injection of thrombin. The PA was likely caused by shearing forces of the dilators, the 14-F Impella sheath and foot of the device. We propose deploying the Perclose device earlier in the process of dilating the access site to avoid such complication. This is one of the first case reports that detail the occurrence and management of a PA with Impella insertion.

AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury.

AMP-activated protein kinase (AMPK) is an important regulator of diverse cellular pathways in the setting of energetic stress. Whether AMPK plays a critical role in the metabolic and functional responses to myocardial ischemia and reperfusion remains uncertain. We examined the cardiac consequences of long-term inhibition of AMPK activity in transgenic mice expressing a kinase dead (KD) form of the enzyme. The KD mice had normal fractional shortening and no heart failure, cardiac hypertrophy, or fibrosis, although the in vivo left ventricular (LV) dP/dt was lower than that in WT hearts. During low-flow ischemia and postischemic reperfusion in vitro, KD hearts failed to augment glucose uptake and glycolysis, although glucose transporter content and insulin-stimulated glucose uptake were normal. KD hearts also failed to increase fatty acid oxidation during reperfusion. Furthermore, KD hearts demonstrated significantly impaired recovery of LV contractile function during postischemic reperfusion that was associated with a lower ATP content and increased injury compared with WT hearts. Caspase-3 activity and TUNEL-staining were increased in KD hearts after ischemia and reperfusion. Thus, AMPK is responsible for activation of glucose uptake and glycolysis during low-flow ischemia and plays an important protective role in limiting damage and apoptotic activity associated with ischemia and reperfusion in the heart.

Safety and feasibility of intra-arterial bivalirudin bolus administration during primary angioplasty.

AIM: We investigated the feasibility and safety of intra-arterial bivalirudin bolus during primary angioplasty. BACKGROUND: Bivalirudin has been shown to be an effective and safe anticoagulant during angioplasty. However, in the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction trial, the bivalirudin group experienced higher acute stent thrombosis rate compared with the heparin and glycoprotein IIb/IIIa inhibitor group. One possible explanation is suboptimal systemic administration. METHODS: To prevent this possibility and to potentially prevent acute stent thrombosis, we administered intra-arterial bivalirudin bolus during primary angioplasty in 100 consecutive patients. RESULTS: Our observational study suggests safety with no bleeding episode and no observed acute stent thrombosis. CONCLUSION: We conclude that intra-arterial bivalirudin bolus during primary angioplasty is safe and could ensure effective systemic delivery of bivalirudin.

Increased vascular access complications in patients with renal dysfunction undergoing percutaneous coronary procedures using arteriotomy closure devices.

BACKGROUND: Arteriotomy closure device (ACD) use has increased following percutaneous transfemoral coronary procedures (PTCP). However, their safety in patients with chronic kidney disease (CKD) is not known. Therefore, we evaluated the complication rates of ACD among patients with CKD. METHODS: Six-hundred ten consecutive patients who underwent PTCP and ACD were retrospectively studied. Patients were grouped according to their creatinine clearance (CrCl in ml/min/1.73 m2) calculated by the Cockcroft-Gault formula using the National Kidney Foundation classification system; Stage I (CrCl > or = 90); Stage II (60-89); Stage III (30-59); Stage IV (15-29); and Stage V (< or = 15). The primary endpoint was the combined incidence of pseudoaneurysm, retroperitoneal hematoma, femoral artery thrombosis, surgical vascular repair, and groin infection. RESULTS: Among 610 patients 283 (46%) underwent PCI. The primary endpoint was seen in 66 (10.8%) patients. Univariate predictors of primary outcome were lower CrCl (p < 0.001), and presence of peripheral vascular disease (p = 0.03). There was an inverse relationship between CrCl and complication rate. CKD was the strongest independent multivariate predictor for the primary endpoint (OR 1.032; 95% CI 1.019-1.046; p < 0.0001), driven by higher infection (p < 0.0001), thrombosis (p = 0.003) and hematoma (p = 0.007). CONCLUSIONS: Renal function appears to be significantly associated with vascular access-site complications. Worsening renal function is associated with higher vascular access site complications, largely driven by an increased infection rate.

Can glycopyrrolate replace temporary pacemaker and atropine in patients at high risk for symptomatic bradycardia undergoing AngioJet mechanical thrombectomy?

We studied the feasibility and efficacy of glycopyrrolate, a synthetic anticholinergic agent with shorter half-life and without reflex tachycardia, in preventing symptomatic bradycardia in patients undergoing mechanical thrombectomy with the AngioJet Rheolytic Thrombectomy System (Possis Medical, Inc., Minneapolis, Minnesota). There was no need for temporary pacemaker insertion and no hemodynamically significant bradycardia in 10 consecutive patients. Additionally, there were no adverse effects from glycopyrrolate therapy. Our pilot study demonstrates that glycopyrrolate may replace temporary pacemaker insertion in these patients at high risk for symptomatic bradycardia.

Activation of AMPK alpha- and gamma-isoform complexes in the intact ischemic rat heart.

AMP-activated protein kinase (AMPK) plays a key role in modulating cellular metabolic processes. AMPK, a serine-threonine kinase, is a heterotrimeric complex of catalytic alpha-subunits and regulatory beta- and gamma-subunits with multiple isoforms. Mutations in the cardiac gamma(2)-isoform have been associated with hypertrophic cardiomyopathy and pre-excitation syndromes. However, physiological regulation of AMPK complexes containing different subunit isoforms is not well defined and is important for an understanding of the function of this signaling pathway in the intact heart. We evaluated the kinase activity associated with heart AMPK complexes containing specific alpha- and gamma-subunit isoforms of AMPK in an in vivo rat model of regional ischemia. Left coronary artery occlusion activated the immunoprecipitated alpha(1)-isoform (6-fold, P < 0.01) and alpha(2)-isoform (9-fold, P < 0.01) in the ischemic left ventricle compared with sham controls. The degree of alpha-subunit activation depended on the extent of ischemia and paralleled echocardiographic contractile dysfunction. The regulatory gamma(1)- and gamma(2)-isoforms were expressed in the heart. The gamma(1)- and gamma(2)-isoforms coimmunoprecipitated with alpha(1)- and alpha(2)-isoforms in proportion to alpha-subunit content. gamma(1)-Isoform immunocomplexes accounted for 70% of AMPK activity and AMPK phosphorylation (Thr(172)) in hearts. Ischemia similarly increased AMPK activity associated with the gamma(1)- and gamma(2)-isoform complexes threefold (P < 0.01 for each). Thus AMPK catalytic alpha(1)- and alpha(2)-isoforms are activated by regional ischemia in vivo in the heart, irrespective of the regulatory gamma(1)- or gamma(2)-isoforms to which they are complexed. Despite the pathophysiological importance of gamma(2)-isoform mutations, gamma(1)-isoform complexes account for most of the AMPK activity in the ischemic heart.

Physiological role of AMP-activated protein kinase in the heart: graded activation during exercise.

AMP-activated protein kinase (AMPK) is emerging as a key signaling pathway that modulates cellular metabolic processes. In skeletal muscle, AMPK is activated during exercise. Increased myocardial substrate metabolism during exercise could be explained by AMPK activation. Although AMPK is known to be activated during myocardial ischemia, it remains uncertain whether AMPK is activated in response to the physiological increases in cardiac work associated with exercise. Therefore, we evaluated cardiac AMPK activity in rats at rest and after 10 min of treadmill running at moderate (15% grade, 16 m/min) or high (15% grade, 32 m/min) intensity. Total AMPK activity in the heart increased in proportion to exercise intensity (P < 0.05). AMPK activity associated with the alpha2-catalytic subunit increased 2.8 +/- 0.4-fold (P < 0.02 vs. rest) and 4.5 +/- 0.6-fold (P < 0.001 vs. rest) with moderate- and high-intensity exercise, respectively. AMPK activity associated with the alpha1-subunit increased to a lesser extent. Phosphorylation of the Thr172-regulatory site on AMPK alpha-catalytic subunits increased during exercise (P < 0.001). There was no increase in Akt phosphorylation during exercise. The changes in AMPK activity during exercise were associated with physiological AMPK effects (GLUT4 translocation to the sarcolemma and ACC phosphorylation). Thus cardiac AMPK activity increases progressively with exercise intensity, supporting the hypothesis that AMPK has a physiological role in the heart.