Ray V. Matthews

Previous Angina Alters In-Hospital Outcome in TIMI 4 A Clinical Correlate to Preconditioning?

BACKGROUND Ischemic preconditioning has been shown to reduce myocardial infarct size in experimental models, but its role in patients remains unclear. Angina before myocardial infarction reflects brief episodes of ischemia and may be a marker of preconditioning. As part of the Thrombolysis in Myocardial Infarction (TIMI) 4 study, we performed an analysis on the effect of a history of previous angina on in-hospital outcomes for patients with acute myocardial infarction. METHODS AND RESULTS Patients eligible for thrombolytic therapy were enrolled into the study. Data were collected from case report forms regarding previous history of angina, in-hospital outcome and 6-week follow-up. Two hundred eighteen patients had a history of previous angina at any time before acute myocardial infarction, and 198 patients did not have previous angina. Patients with any previous history of angina were less likely than with those without angina to experience in-hospital death (3% versus 8%) (P = .03), severe congestive heart failure (CHF) or shock (1% versus 7%, P = .006), or the combined end point of in-hospital death, severe CHF, or shock (4% versus 12%, P = .004). Moreover, patients with any history of angina were more likely to have a smaller creatine kinase (CK)-determined infarct size (119 versus 154 CK integrated units; P = .01) and were less likely to have Q waves on their ECG (57% versus 69%; P = .01). In the subset of patients who experienced angina within the 48 hours before infarction (compared with those who did not), there was a trend toward less likely in-hospital death (3% versus 6%; P = .09), a lower incidence of severe CHF or shock (1% versus 6% P = .008), a lower combined end point of death, CHF, or shock (3% versus 10%; P = .006), smaller infarct size assessed by CK (115 versus 151 CK units; P = .03), and a trend toward fewer Q-wave infarcts. However, patients with a history of previous angina did have a trend toward more recurrent ischemic pain. Of importance is that the beneficial in-hospital effects of previous angina were not dependent on angiographically visible coronary collaterals. CONCLUSIONS Previous angina confers a beneficial effect on in-hospital outcome after acute myocardial infarction. The reasons for this benefit are uncertain, but one potential mechanism for this observation may be ischemic preconditioning.

Influx of neutrophils into the walls of large epicardial coronary arteries in response to ischemia/reperfusion.

BackgroundThere are several clinical situations in which large epicardial coronary arteries are deprived of blood flow, such as occurs when an obstructing thrombus or embolus lodges within a vessel or during coronary dissection. There is little information concerning the effect of flow deprivation on large epicardial coronary arteries. Methods and ResultsWe studied a model in which a segment of a large epicardial coronary artery was deprived of blood flow using both proximal and distal clamps for 3 hours followed by reperfusion. On examination by light microscopy of cross sections of the arteries, 19 ± t6 neutrophils were present in the intima of ischemic/reperfused vessels, whereas only a mean of 4 ± 3 (SEM) were present in the intima of nonischemic vessels (p < 0.02). On average, there were 17 ± 9 neutrophils just under the elastic lamina in ischemic/reperfused vessels versus none in the nonischemic vessels (p < 0.05); there were 16 ± 10 neutrophils present within the media of ischemic/reperfused vessels, and none (p < 0.05) in the nonischemic vessels. Electron microscopic analysis revealed that neutrophils in the ischemic/reperfused vessels were often “sandwiched” between the endothelial cells and the elastic lamina. Ultrastructural abnormalities within the myocardium also revealed damage to the microvasculature, including the presence of neutrophils within the vessels and erythrocyte stasis. To rule out the possibility that findings in the large epicardial arteries were due to toxic substances from static blood within the isolated arterial segment, a protocol was performed in which blood was removed from the isolated segment. Again, neutrophil infiltration into the vessel was observed. Resting mean epicardial coronary artery blood flow before coronary occlusion was 19 ± 3 mVmin; mean coronary blood flow 2.5 hours after reperfusion was identical at 19 ± 3 ml/min. Response to both endothelial-dependent vasodilation (acetylcholine) and endothelial-independent vasodilation (nitroglycerin) challenges was normal early after reperfusion but was depressed late after reperfusion, suggesting progressive vascular dysfunction and hence a form of vascular reperfusion injury in this model. ConclusionsWhen large epicardial coronary arteries are deprived of blood flow, followed by reperfusion in this model, neutrophils migrate into the vessel wall as well as into the microvasculature. These abnormalities are associated with reduced endothelial-dependent and endothelial-independent coronary vasodilator reserve.

Long-term vessel response to a self-expanding coronary stent: A serial volumetric intravascular ultrasound analysis from the ASSURE trial

OBJECTIVES We sought to investigate the in vivo mechanical properties of a new self-expanding coronary stent (RADIUS) and, particularly, the subsequent vessel response over time. BACKGROUND Preclinical studies have suggested that self-expanding stents may produce less vessel wall injury at initial deployment, leading to larger follow-up lumens than with balloon-expandable stents. However, the influence of the chronic stimulus from self-expanding stents on the vessel wall remains unknown. METHODS Sixty-two patients were randomly assigned to either the RADIUS self-expanding stent group (n = 32) or the Palmaz-Schatz balloon-expandable stent group (n = 30). Intravascular ultrasound was performed after stent deployment and at six-month follow-up. RESULTS At follow-up, the RADIUS stents had increased 23.6% in overall volume, while the Palmaz-Schatz stents had remained unchanged. Due to the greater mean neointimal area (3.0 +/- 1.7 mm2 vs. 1.9 +/- 1.2 mm2, p = 0.02) in the RADIUS group, no significant difference in net late lumen loss was observed between the two groups. On the other hand, analysis at the peristent margins demonstrated that mean late loss was significantly smaller in the RADIUS group than it was in the Palmaz-Schatz group (0.1 +/- 2.1 mm2 vs. 1.9 +/- 2.4 mm2, p = 0.02). CONCLUSIONS Serial volumetric IVUS revealed that the RADIUS stents continued to enlarge during the follow-up period. In this stent implantation protocol, this expansion was accompanied by a greater amount of neointima than the Palmaz-Schatz stents, resulting in similar late lumen loss in both configurations. In the peristent margins, however, late lumen loss was minimized with the RADIUS stents.

Evidence for stunned myocardium in humans: a 2001 update.

This article describes clinical situations in which stunning occurs and updates previous reviews on the topic. Stunning following angioplasty, angina and exercise‐induced ischemia, infarction, and after cardiac surgery are described. In addition, newer concepts regarding stunning, including neurogenic stunned myocardium, are discussed. Left atrial stunning following cardioversion is a recently recognized phenomenon with important clinical implications, but differs from the original concept of post‐ischemic stunning.

Left atrial appendage obliteration: mechanisms of healing and intracardiac integration.

OBJECTIVES The objectives of this study were: 1) to delineate the temporal course of histopathologic healing as the left atrial appendage (LAA) is obliterated by a mechanical device; and 2) to compare this process with other intravascular and intracardiac implanted technologies. BACKGROUND Intracardiac device healing is incompletely understood. We thus studied the histopathology of device-based LAA obliteration. METHODS Nine dog hearts were examined over time after LAA device placement and results were compared with human hearts with prior LAA obliteration using the same device. RESULTS At 3 days in dogs, atrial surfaces were covered by fibrin, which sealed gaps between the LA wall and the device and filled the LA appendage cavity. At 45 days, endothelial cells covered the endocardial surface with underlying smooth muscle cells that sealed the device-LA interface. Regions with prior thrombus were replaced by endocardium surrounding the device membrane. Disorganized thrombus remained in the LAA body and at the periphery near the appendage walls. Mild inflammation was observed as thrombus resorbed. By 90 days, a complete endocardial lining covered the former LAA ostium. Organizing thrombus had become connective tissue, with no residual inflammation. The human necropsy hearts had similar findings. In these 4 hearts (139, 200, 480, and 852 days after implant), the ostial fabric membrane was covered with endocardium. The appendage surface contained organizing thrombus with minimal inflammation. Organizing fibrous tissue was inside the LAA cavity, prominent near the atrial wall. The LAA interior contained organizing thrombus. CONCLUSIONS This intracardiac device integration study delineated healing stages of early thrombus deposition, thrombus organization, inflammation and granulation tissue, final healing by connective tissue, and endocardialization without inflammation. These observations may yield insight into cellular healing processes in other cardiac devices.

Reduced distal embolization with transluminal extraction atherectomy compared to balloon angioplasty for saphenous vein graft disease

Extraction atherectomy utilizes suction aspiration as an attempt to limit distal emboli during atherectomy. We sought to test the hypothesis that extraction atherectomy produces less distal embolization than balloon angioplasty when treating saphenous vein grafts. Among 163 consecutive, nonrandomized patients, 103 patients underwent transluminal extraction catheter (TEC) atherectomy with or without adjunctive balloon angioplasty, and 60 patients had conventional balloon angioplasty. Both groups showed comparably high procedural success rates (TEC 90.3%, angioplasty 83.3%, P = NS). TEC cases had a significantly lower incidence of angiographic distal embolization, compared with angioplasty (3.9% vs. 16.7%, P = 0.005). In cases with angiographic evidence of thrombus in the grafts, TEC maintained a significantly lower incidence of distal embolization than angioplasty (5.6% vs. 31.8%, P = 0.004). There were no statistical differences between the two groups regarding the incidence of other procedure-related complications, including death, myocardial infarction, or emergency coronary artery bypass grafting. TEC atherectomy appears to have a significantly lower incidence of distal embolization than balloon angioplasty when treating saphenous vein grafts, particularly in the presence of angiographically apparent thrombus.

Percutaneous left ventricular assist device for high-risk percutaneous coronary interventions: Real-world versus clinical trial experience.

BACKGROUND High-risk percutaneous coronary intervention (PCI) supported by percutaneous left ventricular assist devices offers a treatment option for patients with severe symptoms, complex and extensive coronary artery disease, and multiple comorbidities. The extrapolation from clinical trial to real-world practice has inherent uncertainties. We compared the characteristics, procedures, and outcomes of high-risk PCI supported by a microaxial pump (Impella 2.5) in a multicenter registry versus the randomized PROTECT II trial (NCT00562016). METHODS The USpella registry is an observational multicenter voluntary registry of Impella technology. A total of 637 patients treated between June 2007 and September 2013 were included. Of them, 339 patients would have met enrollment criteria for the PROTECT II trial. These were compared with 216 patients treated in the Impella arm of PROTECT II. RESULTS Compared to the clinical trial, registry patients were older (70 ± 11.5 vs 67.5 ± 11.0 years); more likely to have chronic kidney disease (30% vs 22.7%), prior myocardial infarction (69.3% vs 56.5%), or prior bypass surgery (39.4% vs. 30.2%); and had similar prevalence of diabetes, peripheral vascular disease, and prior stroke. Registry patients had more extensive coronary artery disease (2.2 vs 1.8 diseased vessels) and had a similar Society of Thoracic Surgeons predicted risk of mortality. At hospital discharge, registry patients experienced a similar reduction in New York Heart Association class III to IV symptoms compared to trial patients. Registry patients had a trend toward lower in-hospital mortality (2.7% vs 4.6, P = .27). CONCLUSIONS USpella provides a real-world and contemporary estimation of the type of procedures and outcomes of high-risk patients undergoing PCI supported by Impella 2.5. Despite the higher risk of registry patients, clinical outcomes appeared to be favorable and consistent compared with the randomized trial.

Use of regadenoson for measurement of fractional flow reserve

To compare the use of regadenoson to adenosine for measurement of fractional flow reserve (FFR).

Balloon expandable stents to treat central venous stenoses in hemodialysis patients.

Vascular access failure in hemodialysis patients remains a significant problem. The use of thrombolytic agents and balloon angioplasty instead of or in conjunction with surgical revision, has been helpful in increasing the life span of vascular access in these patients. The application of newer endovascular therapies, such as vascular stents, may further improve the salvage rate of hemodialysis access sites. These stents may be particularly valuable in treating stenoses in large central veins. We present 2 cases in which a balloon-expandable Palmaz stent was used to treat a central venous stenosis causing signs of vascular access failure.

Percutaneous left ventricular support for high-risk PCI and cardiogenic shock: who gets what?

BACKGROUND Temporary use of a percutaneous left ventricular assist device (PLVAD) may be beneficial in patients undergoing high-risk percutaneous coronary intervention (PCI) and those with cardiogenic shock (CS). METHODS Seventy-four consecutive patients undergoing high-risk PCI and those with CS receiving intraaortic balloon pump (IABP), TandemHeart (TH), or Impella device (IMP) were enrolled. Patient undergoing high-risk PCI (n=57) and those treated for CS (n=17) were analyzed as separate cohorts. Patients undergoing IABP-assisted PCI were compared to those undergoing PLVAD (TH and IMP)-assisted PCI. The primary end point was in-hospital major adverse cardiovascular events, and the secondary end point was in-hospital vascular complications. RESULTS For the high-risk PCI cohort (n=57), 22 received PLVAD and 35 received IABP. Patients receiving IABP were younger and less likely to have a prior myocardial infarction (MI) and less likely to be on dialysis compared to those receiving PLVAD support. Patients receiving PLVAD support had a higher baseline Syntax score, had a higher prevalence of unprotected left main disease, underwent treatment of more coronary lesions, received more coronary stents, and more likely received drug-eluting stents compared to those receiving IABP support. The primary and secondary end points were similar between both groups. For the CS cohort (n=17), 4 received PLVAD and 13 received IABP. Patients receiving PLVAD support were more likely to have a prior MI, had a lower ejection fraction, underwent treatment of more coronary lesions, and received more coronary stents compared to those receiving IABP support. The primary and secondary end points were similar between both groups. CONCLUSIONS IABP compared with PLVAD use for high-risk PCI and CS is associated with significantly different baseline patient, clinical, procedural, and angiographic characteristics. In-hospital clinical outcome was similar between both groups in both the high-risk PCI and the CS cohorts. When physicians have access to each of these devices, short-term clinical outcome appears to be similar.