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Fibrosis is the end result of a complex series of events that follow tissue injury and inflammation. Pathophysiologic fibrosis results in permanent scar formation, and can impair organ function. Fibrocytes are circulating, bone-marrow-derived progenitor cells that traffic from the bone marrow to the injured organ via the bloodstream, where they differentiate into fibroblasts and myofibroblasts, and play a pivotal role in both physiologic and aberrant fibrosis. In this review, we focus on the contribution of fibrocytes to fibrotic diseases of the lungs and the heart, including interstitial lung diseases, asthma, pulmonary hypertension, atherosclerosis and ischemic cardiomyopathy.

Background: In patients with chronic ischemic heart disease (IHD), the presence and extent of spontaneously visible coronary collaterals are powerful determinants of clinical outcome. There is marked heterogeneity in the recruitment of coronary collaterals amongst patients with similar degrees of coronary artery stenoses, but the biological basis of this heterogeneity is not known. Chemokines are potent mediators of vascular remodeling in diverse biological settings. Their role in coronary collateralization has not been investigated. We sought to determine whether plasma levels of angiogenic and angiostatic chemokines are associated with of the presence and extent of coronary collaterals in patients with chronic IHD., Methodology/principal Findings: We measured plasma concentrations of angiogenic and angiostatic chemokine ligands in 156 consecutive subjects undergoing coronary angiography with at least one ≥90% coronary stenosis and determined the presence and extent of spontaneously visible coronary collaterals using the Rentrop scoring system. Eighty-eight subjects (56%) had evidence of coronary collaterals. In a multivariable regression model, the concentration of the angiogenic ligands CXCL5, CXCL8 and CXCL12, hyperlipidemia, and an occluded artery were associated with the presence of collaterals; conversely, the concentration of the angiostatic ligand CXCL11, interferon-γ, hypertension and diabetes were associated with the absence of collaterals (ROC area 0.91). When analyzed according to extent of collateralization, higher Rentrop scores were significantly associated with increased concentration of the angiogenic ligand CXCL1 (p<0.0001), and decreased concentrations of angiostatic ligands CXCL9 (p<0.0001), CXCL10 (p = 0.002), and CXCL11 (p = 0.0002), and interferon-γ (p = 0.0004)., Conclusions/significance: Plasma chemokine concentrations are associated with the presence and extent of spontaneously visible coronary artery collaterals and may be mechanistically involved in their recruitment.

Objectives: The goal of this study was to compare whether coronary angiography or noninvasive imaging more accurately identifies coronary artery disease (CAD) and predicts mortality in patients with end-stage renal disease (ESRD) under evaluation for transplantation., Background: CAD is a leading cause of mortality in patients with ESRD. The optimal method for identifying CAD in ESRD patients evaluated for transplantation remains controversial with a paucity of prognostic data currently available comparing noninvasive methods to coronary angiography., Methods: The study cohort consisted of 57 patients undergoing both coronary angiography and stress perfusion imaging. Severe CAD was defined by angiography as ≥ 70% stenosis, and by noninvasive testing as ischemia in ≥ 1 zone. Follow-up for all cause mortality was 3.3 years., Results: On noninvasive imaging, 63% had ischemia. On angiography, 40% had at least one vessel with severe stenoses. Abnormal perfusion was observed in 56% of patients without severe disease angiographically. Noninvasive imaging had poor specificity (24%) and poor positive predictive value (43%) for identifying severe disease. Angiography but not noninvasive imaging predicted survival; 3 year survival was 50% and 73% for patients with and without severe CAD by angiography (p<0.05)., Conclusions: False positive scintigrams limited noninvasive imaging in patients with ESRD. Angiography was a better predictor of mortality compared with noninvasive testing., (Copyright © 2010 Wiley-Liss, Inc.)

Heavy snowfall, cold temperatures, and low atmospheric pressure during the winter months have been associated with increased adverse cardiovascular events. However, only a few cases of the "snow shoveler's infarction" have been reported. The investigators describe their experience with 6 patients presenting with ST elevation myocardial infarctions, all within a 24-hour period during an unprecedented snowfall (4 of whom were shoveling snow), and provide a detailed review of previously reported cases of snow shoveler's infarction. Consistent with other reports, most patients reported here had the traditional cardiac risk factors of hypertension, hyperlipidemia, diabetes mellitus, tobacco use, and sedentary lifestyle. Unique to this case series, however, was that the 4 patients who had histories of coronary artery disease and previous coronary artery stenting all presented with subacute stent thromboses documented on coronary angiography performed emergently. Moreover, these patients constituted 25% of all subacute stent thromboses diagnosed in the cardiac catheterization laboratory in the preceding 12 months. In conclusion, these findings suggest that in typically sedentary individuals with cardiac risk factors or histories of coronary artery disease, snow shoveling may trigger ST elevation myocardial infarction and therefore should be avoided. This may be most critical in patients with histories of coronary stent placement, considering that these findings suggest that snow shoveling may precipitate subacute stent thrombosis.

Regeneration and fibrosis are integral parts of the recovery process following tissue injury, and impaired regulation of these mechanisms is a hallmark of many chronic diseases. A population of bone marrow-derived mesenchymal progenitor cells known as fibrocytes, play an important role in tissue remodeling and fibrosis in both physiologic and pathologic settings. In this review we summarize the key concepts regarding the pathophysiology of wound healing and fibrosis, and present data to support the contention that circulating fibrocytes are important in both normal repair process and aberrant healing and fibrotic damage associated with a diverse set of disease states.

The tumor microenvironment is extremely complex that depends on tumor cell interaction with the responding host cells. Angiogenesis, or new blood vessel growth from preexisting vasculature, is a preeminent feature of successful tumor growth of all solid tumors. While a number of factors produced by both the tumor cells and host responding cells have been discovered that regulate angiogenesis, increasing evidence is growing to support the important role of CXC chemokines in this process. As a family of cytokines, the CXC chemokines are pleiotropic in their ability to regulate tumor-associated angiogenesis, as well as cancer cell metastases. In this chapter, we will discuss the disparate activity that CXC chemokines play in regulating cancer-associated angiogenesis and metastases., (Copyright 2010 Elsevier Inc. All rights reserved.)

Pulmonary fibrosis is associated with a number of disorders that affect the lung. Although there are several cellular types that are involved in the pathogenesis pulmonary fibrosis, the resident lung fibroblast has been viewed traditionally as the primary cell involved in promoting the deposition of ECM that culminates in pulmonary fibrosis. However, recent findings demonstrate that a circulating cell (i.e., the fibrocyte) can contribute to the evolution of pulmonary fibrosis. Fibrocytes are bone marrow-derived mesenchymal progenitor cells that express a variety of cell-surface markers related to leukocytes, hematopoietic progenitor cells, and fibroblasts. Fibrocytes are unique in that they are capable of differentiating into fibroblasts and myofibroblasts, as well as adipocytes. In this review, we present data supporting the critical role these cells play in the pathogenesis of pulmonary fibrosis.

In most cases of acute ST-segment elevation myocardial infarction, only 1 epicardial artery contains an occluding thrombus, commonly referred to as the "culprit" artery. Rarely, however, patients present with >1 acutely thrombosed coronary artery (i.e., "multiple culprits"). The investigators present their experience with 18 patients presenting with ST-segment elevation myocardial infarctions and angiographically documented multiple culprit arteries, provide a detailed review of an additional 29 patients previously reported, and summarize baseline characteristics, pertinent electrocardiographic and angiographic findings, laboratory values, and clinical outcomes for all 47 patients. In this case series, most patients were men (85%) with histories of tobacco use (49%). Although nearly 1/3 of the patients had isolated inferior ST-segment elevation on initial 12-lead electrocardiography, 50% of them had simultaneous thrombotic occlusions of the right coronary and the left anterior descending coronary arteries documented on coronary angiography. These patients were hemodynamically unstable on presentation, with >1/3 in cardiogenic shock. In most cases, no other potential predisposing factors were identified. In conclusion, patients with multiple culprit arteries in the setting of ST-segment elevation myocardial infarctions represent a unique population with high rates of cardiogenic shock and no clear cause.

The purpose of this study is to explore the relationship between coronary artery disease (CAD), transplantation status and subsequent mortality in end-stage renal disease (ESRD) patients undergoing evaluation for renal transplantation. Two hundred fifty-three ESRD patients at high risk for CAD underwent coronary angiography as part of a renal transplant evaluation. The cohort was divided into three groups: Group 1 (n = 127) had no vessels with >or=50% stenosis, Group 2 (n = 56) had one vessel with >or=50% stenosis and Group 3 (n = 70) had two or more vessels with >or=50% stenosis. Long-term survival was determined; median follow-up was 3.3 years. The baseline characteristics were similar except for older age and higher proportion of diabetes mellitus, dyslipidemia and peripheral vascular disease in Groups 2 and 3 patients as compared to Group 1. Survival was worse in Group 3 compared to Group 1 (p < 0.0001). Each of the three subgroups had better survival with renal transplantation than those who did not undergo transplantation (p < 0.0001). Although the degree of CAD is related to subsequent mortality, transplantation is associated with better survival regardless of the extent and severity of CAD. Thus, the presence of CAD should not exclude ESRD patients from consideration for this therapy.

Fibrocytes are bone marrow-derived mesenchymal progenitor cells that express markers of leukocytes, haematopoietic progenitor cells, and fibroblasts. They play a pivotal role in tissue remodelling and fibrosis in both physiologic and pathologic settings. Fibrocytes are unique in that they are capable of differentiating into fibroblasts and myofibroblasts, as well as adipocytes. In this review we will present data supporting the critical role they play in the pathogenesis of chronic inflammatory fibrotic diseases of the lungs, heart and vasculature.

Background: Timely reperfusion in ST-segment elevation myocardial infarction (STEMI) patients improves clinical outcomes. Implementing strategies to target institutional-specific delays are crucial for improved patient care., Methods and Results: Using a novel strategy to analyze specific components of door-to-balloon time (DBT) at our institution, we previously identified several specific interval delays in our prior STEMI protocol. We then implemented 4 strategies to reduce DBT: (1) emergency department physician activation of the STEMI protocol; (2) "single call" broadcast paging of the STEMI team by the page operator; (3) immediate feedback to the emergency and cardiology departments with joint monthly quality improvement meetings; and (4) transfer of the off-hours STEMI patient directly to the laboratory on activation by an in-hospital team. After implementation of the new protocol, we examined each component time interval from the first 59 consecutive STEMI patients treated with the new protocol between March 2007 and June 2008 and compared time intervals with the previous 184 STEMI patients. Compared with the previous 184 STEMI patients, the median DBT of the subsequent 59 STEMI patients significantly improved from 125 to 86 minutes (P<0.0001). This improvement was largely driven by a decrease in the interval from the initial 12-lead ECG to activation of the on-call catheterization team (from 40 to 11 minutes, P<0.0001)., Conclusions: After examining specific component delays in our institution's DBT, we were able to successfully use quality improvement strategies to focus on specific sources of delay in our institution. This dramatically improved our median DBT toward the goal of achieving a guideline-recommended <90 minutes for all patients.

The resident fibroblast has been traditionally viewed as the primary cell involved in promoting pulmonary fibrosis. However, contemporary findings now support the concept of a circulating cell (fibrocyte) that also contributes to pulmonary fibrosis. Fibrocytes are bone marrow-derived mesenchymal progenitor cells that express a variety of cell surface markers related to leukocytes, hematopoietic progenitor cells and fibroblasts. Fibrocytes are unique in that they are capable of differentiating into fibroblasts and myofibroblasts, as well as adipocytes. In this review, we present data supporting the critical role these cells play in the pathogenesis of pulmonary fibrosis.

Objectives: To assess the influence of acute hypoxemia on the dimensions of diseased and nondiseased coronary arterial segments in humans., Methods: In 18 subjects (age 53 +/- 8 years) with known or suspected coronary artery disease, quantitative coronary angiography was performed before and after being randomly assigned to breathing (1) an inspired oxygen concentration (fraction of inspired oxygen, FIO2) of 21% (room air, RA) for 20 min (n = 4, controls) or (2) an FIO2 of 15 and 10% for 10 min each (corresponding to altitudes of 2,500 and 5,500 m, respectively; n = 14)., Results: In the control subjects, no hemodynamic, oximetric or angiographic variable changed. In the 14 study subjects, the arterial partial pressure of oxygen averaged 85 +/- 13 mm Hg on RA, 65 +/- 15 mm Hg on 15% FIO2 and 44 +/- 13 mm Hg on 10% FIO2. Average arterial segment diameter was 2.52 +/- 0.63 mm on RA, 2.55 +/- 0.62 mm on 15% FIO2 (not significant vs. RA) and 2.66 +/- 0.66 mm on 10% FIO2 (p < 0.001 vs. RA). The increase in coronary arterial diameter with 10% FIO2 occurred only in normal segments (2.74 +/- 0.64 vs. 2.97 +/- 0.64 mm; p < 0.001), but not in diseased segments (2.34 +/- 0.57 vs. 2.38 +/- 0.55 mm; not significant)., Conclusions: In humans, severe hypoxemia induces vasodilation of angiographically normal coronary arterial segments, whereas it causes no change in diseased segments., (Copyright 2008 S. Karger AG, Basel.)

Chemokines are a superfamily of homologous heparin-binding proteins, first described for their role in recruiting leukocytes to sites of inflammation. Chemokines have since been recognized as key factors mediating both physiological and pathological neovascularization in such diverse clinical settings as malignancy, wound repair, chronic fibroproliferative disorders, myocardial ischemia, and atherosclerosis. Members of the CXC chemokine family, structurally defined as containing the ELR amino acid motif, are potent inducers of angiogenesis, whereas another subset of the CXC chemokines inhibits angiogenesis. In addition, CCL2, a CC chemokine ligand, has been implicated in arteriogenesis. In this article, we review the current literature on the role of chemokines as mediators of neovascularization.

A 40-year-old African-American woman presented with atypical chest pain, an acute non-ST segment elevation myocardial infarction, and angiographic evidence for severe ostial vasospasm of the left main and right coronary arteries. Subsequently, she was diagnosed with hyperthyroidism and treated with antithyroid therapy and oral nitrates. Repeat angiography revealed resolution of the vasospasm; however, the chest pain recurred in the euthyroid state. Hyperthyroidism-associated coronary vasospasm is a rare disorder that characteristically causes angina in young Asian women and resolves with correction of hyperthyroidism. We present an atypical case of an African-American woman presenting with a myocardial infarction who developed recurrent angina while euthyroid.

Background: Most hospitals that perform primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) in the United States exceed the recommended door-to-balloon time. There is heightened interest in identifying and eliminating factors that introduce delay., Methods: We performed a key process analysis of our primary PCI program, assessed the relative contribution of individual time intervals on total ischemic time, and identified predictors of delay., Results: Median times and predictors of delay within each time interval were determined for the entire STEMI cohort ("real world") and after exclusion of patients with atypical symptoms and/or presentations of STEMI that resulted in inherent delay in diagnosis and treatment ("ideal world"). Delays in therapy were symptom onset to presentation (120 minutes [interquartile range, IQR, 60-310 minutes, ideal world] and 150 minutes [IQR 60-360 minutes, real world]; predictors of delay were peripheral vascular disease, self-transportation, daytime and weekend presentation); door-to-balloon time (118.5 minutes [IQR 96-141 minutes, ideal world] and 125 minutes [IQR 100-170 minutes, real world]; predictors of delay were female sex, previous stroke, nighttime and weekend presentation, and cardiogenic shock); and symptom onset to first balloon inflation (272 minutes [IQR 187-465 minutes, ideal world] and 297 minutes [IQR 198-560 minutes, real world]; predictors of delay were peripheral vascular disease, weekend presentation, and self-transportation)., Conclusions: Key process analysis of a primary PCI program identifies treatment delays unique to the hospital and the patient population it serves.

Glucose-insulin-potassium (GIK) infusion favourably affects several biomarkers associated with risk in the setting of myocardial infarction (MI). In the context of a recent trial demonstrating no benefit of GIK, we assessed the impact of GIK on inflammation, neurohormonal activation and myonecrosis in ST elevation myocardial infarction (STEMI). In a local substudy of an international randomised trial, 25 patients with STEMI were randomised to receive a 24-hour infusion of GIK vs. no GIK. C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin T (TnT) were assayed at baseline and at 24 hours. The two groups were well matched for baseline characteristics and infarct location. There were no statistically significant differences at baseline or at 24 hours in levels of hs-CRP, NT-proBNP or cTnT, with similar and significant increases in all three biomarkers by 24 hours in both groups. In conclusion, GIK had no discernible effect on biomarkers associated with inflammation, neurohormonal activation or myonecrosis, three pathways associated with adverse outcomes in STEMI.

Previous studies have shown that compared with white patients, non-white patients with ST elevation myocardial infarction (STEMI) have worse clinical outcomes. Differences in co-morbidities, extent and severity of coronary artery disease, health insurance, and socioeconomic status have been identified as possible reasons for this disparity. However, an alternative explanation for such observed disparities in outcomes could be differences in process of care. For example, in most of these studies, non-white patients were less likely to receive reperfusion therapy, and if treated, were more likely to receive thrombolysis than to undergo primary percutaneous coronary intervention (PCI). We hypothesized that if all patients were treated similarly with primary PCI, there would be no difference in clinical outcomes. We analyzed the demographic, angiographic, in-hospital clinical outcomes, and long-term mortality rates of a racially diverse group of patients presenting to the same hospital with STEMI, all of whom were treated with primary PCI. Our data demonstrate that compared with white patients, non-white patients with STEMI who undergo primary PCI have similar in-hospital clinical outcomes and one-year mortality. This suggests that the previously observed differences in mortality rates may be, at least in part, attributable to differences in the process of care, and not solely to differences in patient factors or differential therapeutic effects.

Patients with left bundle branch block (LBBB) and concomitant coronary artery disease (CAD) have a worse prognosis than those with LBBB without CAD. In addition, subjects with CAD and concomitant LBBB have a higher cardiovascular mortality than those with a similar extent of CAD but without LBBB. Because the presence of LBBB makes the noninvasive identification of CAD problematic, patients with LBBB often are referred for coronary angiography to assess the presence and severity of CAD. To determine the clinical and demographic variables that might help identify those with CAD, we analyzed data from 336 consecutive patients with LBBB referred for coronary angiography. Of the 336, 54% had CAD. In conclusion, those with CAD were likely to be older, Caucasian, and men; they were more likely to have angina pectoris, myocardial infarction, and diabetes mellitus; and they were more likely to have a left ventricular ejection fraction <0.50. In contrast, patients with heart failure were less likely to have CAD.

In patients who have ST-segment elevation myocardial infarction (STEMI), a patent infarct-related artery on the initial angiogram is associated with improved clinical outcomes, including decreased mortality. The present study assessed the influence of administering aspirin, beta blockers, statins, and angiotensin-converting enzyme inhibitors before STEMI on infarct-related artery patency. Our data demonstrate that patients who have STEMI and receive these medications on an outpatient basis before the event have a higher likelihood of having a patent infarct-related artery compared with patients who do not receive these medications. Further, our data demonstrate a graded association according to the number of such medications being administered: the likelihood of a patent infarct-related artery increased to >50% as the number of these medications increased.

To determine the effect of glucose-insulin-potassium infusion on circulating levels of free fatty acids in the setting of contemporary management of ST-elevation myocardial infarction, we randomly assigned 20 patients who were undergoing primary angioplasty to glucose-insulin-potassium infusion or to standard care. Treatment with glucose-insulin-potassium was associated with significantly lower levels of free fatty acid after 24 hours compared with standard care.

According to data from randomized, controlled trials, primary percutaneous coronary intervention (PCI) is the treatment of choice for ST-segment elevation myocardial infarction (MI). In these trials, 1 life was saved and 2 other life-threatening complications, including stroke and reinfarction, were prevented for every 50 patients with ST-segment elevation MI treated with primary PCI rather than thrombolytic therapy. Only 1 major bleeding episode occurred. How can these superior results be realized outside the context of randomized trials? We anticipate 4 obstacles to instituting primary PCI as the universal treatment of ST-segment elevation MI: 1) lack of timely availability, 2) technical expertise of center and operator, 3) the need to address patient subgroups that are not studied in randomized trials, and 4) comparisons of primary PCI to newer pharmacologic regimens. We propose 3 strategies to increase the availability of this procedure: 1) perform primary PCI in qualified community hospitals without surgical back-up; 2) transfer patients from community hospitals without primary PCI capability to hospitals with primary PCI capability; and 3) develop a universal system in which ambulances directly transfer patients to a regional primary PCI center, not necessarily to the closest hospital, similar to the system used for trauma patients. We contend that, in light of the superior clinical outcomes seen with primary PCI for treating ST-segment elevation MI, this procedure should be available to all patients with ST-segment elevation MI and efforts should be made to institute these measures.

There is a remarkable lack of randomized trial data on optimal management of coronary artery disease (CAD) in patients with chronic kidney disease (CKD). In fact, patients with CKD are often excluded from randomized trials that compare different treatment strategies for CAD. Because the most common cause of death in CKD patients is cardiovascular disease, it is crucial that studies are designed to determine the best therapy for CAD in this high-risk group. This article discusses the available data on coronary revascularization outcomes in CKD patients.

Patients with coronary artery disease (CAD) and concomitant left bundle branch block have increased mortality compared with those with CAD but without left bundle branch block. We retrospectively analyzed the extent of CAD in 200 patients with left bundle branch block referred for coronary angiography. Only 13% had left main or 3-vessel CAD. These findings were irrespective of left ventricular (LV) function. Of the 65 patients with normal LV function, only 5 (8%) had left main or 3-vessel disease, and of the 135 patients with depressed LV function, only 21 (16%) had left main or 3-vessel disease.

Patients with end-stage renal disease (ESRD) are at increased risk of death from cardiac causes. Traditionally, coronary artery disease (CAD) in this patient population has been treated conservatively. Despite the scope and complexity of the problem highlighted from large databases, there is a paucity of controlled, randomized data in patients with ESRD. In this paper we address the following two questions: 1) Should the patient with ESRD and CAD be treated with medical therapy or with mechanical revascularization? and 2) Which mechanical revascularization procedure is optimal- surgical or percutaneous? Although the mortality data in favor of coronary revascularization in patients with ESRD and clinically significant CAD is convincing, the data are based solely on retrospective analyses with relatively small numbers of patients. For now, the choice of the revascularization procedure itself must be individualized, taking into consideration such factors as comorbid conditions, coronary anatomy, and the likelihood of achieving complete revascularization. Data from large, prospective, randomized controlled trials are desperately needed to appropriately address the optimal application of coronary revascularization in patients with ESRD.

The primary goal of therapy for acute ST segment elevation myocardial infarction is to preserve left ventricular systolic function and to decrease mortality by achieving rapid, complete, and sustained restoration of blood flow in the infarct-related artery. Early studies assessing the safety and efficacy of combining full-dose thrombolytic therapy with primary percutaneous transluminal coronary angioplasty (PTCA) were disappointing due to an increased incidence of abrupt closure, reinfarction, emergent coronary bypass surgery, and mortality. The observation that the presence of normal coronary blood flow at the time of primary PTCA is an independent predictor of survival coupled with interest in the patency of the downstream microvasculature has prompted investigators to revisit the concept of combining pharmacologic and mechanical strategies. The adjunctive use of pharmacologic therapy with mechanical reperfusion has been coined facilitated primary PTCA and involves the use of reduced-dose thrombolytics, platelet glycoprotein IIb/IIIa inhibitors, or both. The primary goal is to achieve pharmacologic reperfusion before performing definitive mechanical reperfusion. While the preliminary data presented is promising, we must await the results of ongoing large, randomized trials that have been specifically designed to address this question.

Objectives: The purpose of this study was to examine the long-term clinical outcome after percutaneous intervention of saphenous vein grafts (SVG) and to identify the predictors of major adverse cardiac events (MACE)., Background: Percutaneous interventions of SVGs have been associated with more procedural complications and higher restenosis rates compared with interventions on native vessels., Methods: From 1993 to 1997, 1,062 patients underwent percutaneous intervention on 1,142 SVG lesions. Procedural, in-hospital and long-term clinical outcomes were recorded in a database and analyzed., Results: In-hospital MACE occurred in 137 patients (13%) including death (8%), Q-wave myocardial infarction (MI) (2%) and coronary artery bypass surgery (3%). Late MACE occurred in 565 patients (54%) including death (9%), Q-wave MI (9%) and target vessel revascularization (36%). Any MACE occurred in 457 (43%) patients. Follow-up was available in 1,056 (99%) patients at 3 +/- 1 year. Univariate predictors were restenotic lesion (odds ratio [OR]: 2.47, confidence interval [CI]: 1.13 to 3.85, p = 0.0003), unstable angina (OR: 1.99, CI: 1.27 to 2.91, p = 0.04) and congestive heart failure (CHF) (OR: 1.97, CI: 1.14 to 3.24, p = 0.02) for in-hospital MACE, and peripheral vascular disease (PVD) (OR: 2.18, CI: 1.34 to 3.44, p = 0.002), intra-aortic balloon pump placement (OR: 2.08, CI: 1.13 to 3.85, p = 0.02) and previous MI (OR: 1.97, CI: 1.14 to 3.25, p = 0.007) for late MACE. Independent multivariate predictors for late MACE were restenotic lesion (relative risk [RR] 1.33, p = 0.02), PVD (RR: 1.31, p = 0.01), CHF (RR: 1.42, p = 0.01) and multiple stents (RR: 1.47, p = 0.004). Angiographic follow-up was available for 422 patients. Angiographic restenosis occurred in 122 (29%) of stented SVGs and 181 (43%) of nonstented SVGs (p = 0.04). Stent implantation did not confer a survival benefit., Conclusions: Despite the use of new interventional devices, SVG interventions are associated with significant morbidity and mortality; SVG stenting is not associated with better three-year event-free survival. This may be due to progressive disease at nonstented sites.

Sympathetic and parasympathetic reinnervation of the transplanted heart were evaluated by assessing time and frequency domain measurements of heart rate variability at 5 and 8 years. Continuous 24-hour ECG measurements were performed in 13 patients (57 +/- 6 months and 90 +/- 7 months) after orthotopic cardiac transplantation and in 22 healthy age and gender-matched controls, and were analyzed for heart rate variability in the time and frequency domains. Heart rate variability measures reflective of sympathetic reinnervation were sub-normal at 5 years and unchanged at 8 years: those reflective of parasympathetic reinnervation were absent.

Percutaneous revascularization of protected and unprotected left main coronary arteries is associated with acceptable immediate results, but there are significant long-term consequences, including the need for repeat percutaneous intervention (10%), myocardial infarction (7.5%), coronary artery bypass surgery (7%), and death (38%), despite the elective or emergent nature of the procedure.

Objectives: This study was designed to determine the incidence and to quantitate aortic debris retrieved during placement of guiding catheters in patients undergoing percutaneous interventions., Background: Studies have shown that atherosclerotic aortic debris predisposes patients to spontaneous or procedurally related ischemic events., Methods: In 1,000 consecutive percutaneous interventions, the amount of visible atheromatous material from large-lumen-guiding catheters was recorded. Clinical characteristics and in-hospital complications were prospectively collected and associated with debris production., Results: Visible aortic debris (1+ to 3+) occurred more frequently with the Judkins left (JL) catheter, followed by the multipurpose (Multi) catheter compared to any other type of guiding catheter (65%, p = 0.001 and 60%, p = 0.01, respectively). Large debris (2+ and 3+) was observed most frequently with the Multi (odds ratio 3.79, C.I. = 2.32 to 6.21, p = 0.001), JL (odds ratio 2.83, C.I. = 1.98 to 4.05, p = 0.001) and voda left (VL) (odds ratio 2.73, C.I. = 1.51 to 4.95, p = 0.001) catheters. The Judkins right (JR) catheter type was least likely to produce any debris (24%, p = 0.001). A history of unstable angina (p = 0.05) or myocardial infarction (p = 0.003) was associated with a decreased incidence of debris production. The presence of debris was not found to be associated with in-hospital ischemic complications., Conclusions: Studies have shown that atherosclerosis of the aorta is a potential source of systemic embolism in patients undergoing cardiac catheterization. Our study shows that in more than 50% of percutaneous revascularization procedures, guiding catheter placement is associated with scraping debris from the aorta. Design characteristics of the JL, Multi and VL guiding catheters make them most likely to produce such debris. Meticulous attention to allow the debris to exit the back of the catheter is essential to prevent injecting atheromatous debris into the vascular bed.

Scatterplots (displays of each RR interval as a function of the preceding RR interval) provide a visual assessment of nonrandom variations in heart rate. In a recent study, scatterplot length, width, and area correlated with time-domain measures of heart rate variability (HRV) in survivors of recent myocardial infarction (MI) receiving a beta blocker. We performed this study to (1) assess the relation between time-domain measures of HRV and scatterplot indexes in survivors of remote MI not receiving metoprolol and (2) to determine if metoprolol influenced scatterplot indexes. In 28 survivors of remote MI, HRV time-domain variables and scatterplot indexes were measured after 2 weeks off and 2 weeks on metoprolol. Off metoprolol, scatterplot length correlated with long-term HRV variables (SD of the difference of all RR intervals [r = 0.98], SD of the average of all 5-minute intervals [r = 0.97]), and scatterplot width correlated with short-term HRV variables (root-mean-square successive differences between RR intrevals [rMSSD] [r = 0.88]). Metoprolol increased time-domain HRV variables (mean RR interval, rMSSD, and proportion of adjacent RR intervals differing by > 50 ms [pNN50 (%)]) but did not alter scatterplot indexes. Thus, scatterplot indexes correlate with time-domain measures of HRV in survivors of remote MI not receiving metoprolol. In contrast to HRV time-domain variables, scatterplot indexes are not influenced by metoprolol.

Purpose: Nicotine replacement therapy has become a popular therapy for smokers attempting to stop smoking. Unfortunately, some subjects continue to smoke while receiving it. Since nicotine is believed to be the primary constituent of cigarette smoke responsible for its acute adverse effects on myocardial oxygen supply and demand, concomitant nicotine replacement therapy and smoking theoretically could provoke a marked decrease in myocardial oxygen supply and increase in demand. This study was performed to assess the effects of cigarette smoking with and without concomitant intranasal nicotine spray on: (a) myocardial oxygen demand, (b) coronary arterial dimensions, and (c) the development of acute cardiovascular tolerance., Patients and Methods: In 19 smokers referred for cardiac catheterization for the evaluation of chest pain, we assessed the effects of cigarette smoking with and without concomitant intranasal nicotine spray on: (a) heart rate-systolic arterial pressure product (an estimate of myocardial oxygen demand), (b) coronary arterial dimensions (measured with computer-assisted quantitative arteriography), and (c) the development of acute cardiovascular tolerance., Results: Smoking a first cigarette increased rate pressure product (P < 0.001) and decreased coronary arterial dimensions (P < 0.0001). Subsequently, neither variable was altered by intranasal nicotine spray or a second cigarette. Despite a substantial increase in serum nicotine concentration with nicotine spray and smoking, acute cardiovascular tolerance appears to develop., Conclusions: Cigarette smoking causes an increase in myocardial oxygen demand and concomitant coronary arterial vasoconstriction. However, further increases in the serum nicotine concentration do not cause a greater increase in demand or decrease in coronary arterial dimensions. These data suggest that humans acutely develop tolerance to an increasing nicotine concentration, thereby helping to explain the apparent lack of a potential synergistic adverse effect associated with continued smoking during nicotine replacement therapy.

We assessed the influence of metoprolol on heart rate variability in survivors of remote myocardial infarction. In 43 survivors of myocardial infarction 12 to 18 months previously (26 men and 17 women, aged 38 to 69 years), two 24-hour ambulatory electrocardiograms were recorded 2 weeks apart. In patients in group A (n=28), who had taken metoprolol for the previous year, the drug was discontinued for 2 weeks, after which the first recording was done. The second recording was done 2 weeks after metoprolol was resumed. In patients in group B (n=15), who had not taken metoprolol for the previous year, it continued to be withheld, and two 24-hour recordings were done 2 weeks apart. In group A, metoprolol increased the time domain variables indicative of enhanced vagal tone; root-mean-square successive difference in normal RR (NN) intervals was 20 +/- 11 ms (mean +/- SD) without and 24 +/- 9 ms with metoprolol (p<0.05), and the proportion of NN that differ by >50 ms (pNN50%) was 3.6 +/- 6.0 without and 5.5 +/- 6.0 with metoprolol (p<0.05). In the frequency domain, the logarithms of the 24-hour very low frequency and the 24-hour high-frequency power (reflecting parasympathetic activity) were increased (5.12 +/- 1.03 and 4.48 +/- 1.51, respectively, without metoprolol; 5.32 +/- 0.99 and 4.83 +/- 1.24, respectively, with metoprolol, p <0.05 for both). Thus, in survivors of remote myocardial infarction, metoprolol enhances parasympathetic cardiac activity in the time and frequency domain measures of heart rate variability.

Left ventricular mural thrombus is a well-recognized complication of acute myocardial infarction. In survivors of infarction, the incidence with which mural thrombus occurs is influenced by the location and magnitude of infarction, so that it occurs commonly in those with large anterior Q-wave infarctions, particularly in the presence of a left ventricular aneurysm. Echocardiography, radionuclide imaging with indium-111 labeled platelets, computerized tomography, and magnetic resonance imaging may be used to identify a left ventricular mural thrombus. Acute and chronic anticoagulation with heparin and warfarin, respectively, is given to prevent further thrombus formation and to reduce the incidence of systemic embolization.