Cell therapy for human ischemic heart diseases: critical review and summary of the clinical experiences.

A decade ago, stem or progenitor cells held the promise of tissue regeneration in human myocardium, with the expectation that these therapies could rescue ischemic myocyte damage, enhance vascular density and rebuild injured myocardium. The accumulated evidence in 2014 indicates, however, that the therapeutic success of these cells is modest and the tissue regeneration involves much more complex processes than cell-related biologics. As the quest for the ideal cell or combination of cells continues, alternative cell types, such as resident cardiac cells, adipose-derived or phenotypic modified stem or progenitor cells have also been applied, with the objective of increasing both the number and the retention of the reparative cells in the myocardium. Two main delivery routes (intracoronary and percutaneous intramyocardial) of stem cells are currently used preferably for patients with recent acute myocardial infarction or ischemic cardiomyopathy. Other delivery modes, such as surgical or intravenous via peripheral veins or coronary sinus have also been utilized with less success. Due to the difficult recruitment of patients within conceivable timeframe into cardiac regenerative trials, meta-analyses of human cardiac cell-based studies have tried to gather sufficient number of subjects to present a statistical compelling statement, reporting modest success with a mean increase of 0.9-6.1% in left ventricular global ejection fraction. Additionally, nearly half of the long-term studies reported the disappearance of the initial benefit of this treatment. Beside further extensive efforts to increase the efficacy of currently available methods, pre-clinical experiments using new techniques such as tissue engineering or exploiting paracrine effect hold promise to regenerate injured human cardiac tissue.

Cost-effectiveness of percutaneous coronary intervention with drug-eluting stents in patients with multivessel coronary artery disease compared to coronary artery bypass surgery five-years after intervention.

OBJECTIVES: Cost-effectiveness of percutaneous coronary intervention (PCI) using drug-eluting stents (DES), and coronary artery bypass surgery (CABG) was analyzed in patients with multivessel coronary artery disease over a 5-year follow-up. BACKGROUND: DES implantation reducing revascularization rate and associated costs might be attractive for health economics as compared to CABG. METHODS: Consecutive patients with multivessel DES-PCI (n = 114, 3.3 ± 1.2 DES/patient) or CABG (n = 85, 2.7 ± 0.9 grafts/patient) were included prospectively. Primary endpoint was cost-benefit of multivessel DES-PCI over CABG, and the incremental cost-effectiveness ratio (ICER) was calculated. Secondary endpoint was the incidence of major adverse cardiac and cerebrovascular events (MACCE), including acute myocardial infarction (AMI), all-cause death, revascularization, and stroke. RESULTS: Despite multiple uses for DES, in-hospital costs were significantly less for PCI than CABG, with 4551 €/patient difference between the groups. At 5-years, the overall costs remained higher for CABG patients (mean difference 5400 € between groups). Cost-effectiveness planes including all patients or subgroups of elderly patients, diabetic patients, or Syntax score >32 indicated that CABG is a more effective, more costly treatment mode for multivessel disease. At the 5-year follow-up, a higher incidence of MACCE (37.7% vs. 25.8%; log rank P = 0.048) and a trend towards more AMI/death/stroke (25.4% vs. 21.2%, log rank P = 0.359) was observed in PCI as compared to CABG. ICER indicated 45615 € or 126683 € to prevent one MACCE or AMI/death/stroke if CABG is performed. CONCLUSIONS: Cost-effectiveness analysis of DES-PCI vs. CABG demonstrated that CABG is the most effective, but most costly, treatment for preventing MACCE in patients with multivessel disease.

Inhaled iloprost for patients with precapillary pulmonary hypertension and right-side heart failure.

BACKGROUND: Pulmonary hypertension (PH) can lead to right-side heart failure (RHF) and death. There are no therapeutic recommendations for patients experiencing acute RHF in the course of PH. This study aimed to examine the safety and efficacy of inhaled iloprost in patients with precapillary PH and RHF. METHODS AND RESULTS: Between October 2007 and December 2008, 7 patients with precapillary PH and RHF were enrolled. Per protocol, iloprost was inhaled hourly for a minimum of 12 hours during a 24-hour period. The starting dose of 2.5 µg was increased hourly by 2.5 µg as long as the increases were tolerated. Safety and efficacy were determined by continuous invasive monitoring of systemic and pulmonary hemodynamic parameters. Systemic pressures remained stable during inhalation (66.1 ± 6.9 mm Hg at baseline and 69.1 ± 6.4 mm Hg immediately after inhalation therapy, P = 0.48). Cardiac index increased from 2.4 ± 0.7 L/min/m(2) to 2.9 ± 0.9 L/min/m(2) (P = .008). Pulmonary vascular resistance decreased from 634.6 ± 218.3 dyn·s·cm(-5) to 489.6 ± 173.8 dyn·s·cm(-5) (P = .044), and N-terminal B-type natriuretic peptide levels decreased from 13,591 ± 10,939 pg/mL to 9,944 ± 8,569 pg/mL (P = .051). CONCLUSION: Blood pressure-guided hourly inhalation of iloprost may offer a safe and effective strategy for the treatment of PH patients with RHF.

Plasma MMP-9 and TIMP-1 levels on ICU admission are associated with 30-day survival.

BACKGROUND: Matrix metalloproteinases (MMPs) are involved in systemic inflammatory responses and organ failure. The aim of this study was to evaluate early circulating plasma levels of MMP­2, MMP­9 and their inhibitors TIMP­1 and TIMP­2 and their prognostic significance in critically ill patients on admission to the intensive care unit (ICU). METHODS: In a single center prospective study 120 consecutive patients (72.5% male, mean age 66.8 ± 13.3 years, mean simplified acute physiology score [SAPS II] score 52.9 ± 21.9) were enrolled on transfer to the ICU of a cardiology department. The most common underlying conditions were cardiac diseases (n = 42.5%), respiratory failure (n = 10.8%) and sepsis (n = 6.7%). Blood samples were taken within 12 h of ICU admission. The MMP­2, MMP­9, TIMP­1 and TIMP­2 levels in plasma were evaluated in terms of 30-day survival, underlying condition and clinical score. RESULTS: On ICU admission 30-day survivors had significantly lower plasma MMP­9 (odds ratio, OR 1.67 per 1 SD; 95% confidence interval, CI 1.10-2.53; p = 0.016) and TIMP­1 (OR 2.15 per 1 SD; 95% CI 1.27-3.64; p = 0.004) levels than non-survivors; furthermore, MMP­9 and TIMP­1 correlated well with SAPS II (both p < 0.01). In patients with underlying cardiac diseases, MMP­9 (p = 0.002) and TIMP­1 (p = 0.01) were independent predictors of survival (Cox regression). No significant correlation was found between MMP­2 and TIMP­2 levels, MMP/TIMP ratios and 30-day mortality. CONCLUSION: The MMP­9 and TIMP­1 levels are significantly elevated in acute critical care settings with increased short-term mortality risk, especially in patients with underlying heart disease. These findings support the value of MMPs and TIMPs as prognostic markers and potential therapeutic targets in conditions leading to systemic inflammation and acute organ failure.

Mild hyperhomocysteinemia is associated with a decreased fibrinolytic activity in patients after ST-elevation myocardial infarction.

BACKGROUND: Elevated homocysteine (Hcy) levels have been associated with increased risk for cardiovascular disease and it has been shown that hyperhomocysteinemia is associated with increased levels of t-PA antigen in individuals without evidence for coronary artery disease (CAD). The aim of this study was to examine if Hcy plasma levels are associated with plasma levels of fibrinolytic factors in patients with CAD and a history of acute myocardial infarction. METHODS: We measured in 56 patients with CAD, 1 month after their first ST-elevation myocardial infarction, plasma levels of Hcy, the fibrinolytic parameters tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-type-1 (PAI-1), and t-PA-PAI-1 complexes. RESULTS: Hcy plasma levels inversely correlated with t-PA activity (r=-0.303, p<0.05). Patients with mild hyperhomocysteinemia (Hcy>15 micromol/L, n=8) showed significantly lower plasma levels of t-PA activity (p<0.05). Regression analysis revealed that out of cardiovascular risk factors and medical treatment only Hcy was significantly associated with t-PA activity. CONCLUSIONS: Patients with CAD after a first myocardial infarction and hyperhomocysteinemia show a reduced t-PA activity independently from cardiovascular risk factors and medical treatment. Homocysteine lowering therapies may increase fibrinolytic activity and thereby may help to avoid atherothrombotic events in patients with CAD after a first myocardial infarction.

Premature compared with late onset of coronary artery disease: young patients show a severe defect in fibrinolytic response to venous occlusion.

Inflammatory processes play a role in the onset of acute cardiovascular events associated with activation of the coagulation system whereas the fibrinolytic system may prevent local thrombus formation. We compared 25 patients with premature coronary artery disease (CAD) (first ST-elevation myocardial infarction, < 55 years old) with 25 sex-matched patients older than 55 years at their first myocardial infarction. Six months after the acute event, patients with late onset of CAD showed a significantly higher increase of tissue-type plasminogen activator activity during venous occlusion compared with patients with premature CAD (P < 0.005). Prothrombin fragment 1+2 was higher in patients with late-onset CAD (P < 0.05), whereas the inflammatory markers C-reactive protein and soluble intercellular cell adhesion molecule-1 were not different in both groups. A multivariate analysis including cardiovascular risk factors showed that the tissue-type plasminogen activator response to venous occlusion was independently associated with patient age at onset of first ST-elevation myocardial infarction. Although in our series high age was associated with a prothrombotic state, a high fibrinolytic capacity might have some beneficial effect and contribute to a delayed onset of adverse cardiovascular events in these patients.

An increase of C-reactive protein is associated with enhanced activation of endogenous fibrinolysis at baseline but an impaired endothelial fibrinolytic response after venous occlusion.

OBJECTIVES: The goal of this study was to determine whether chronic inflammation of the vascular wall may be associated with an impaired activation of the fibrinolytic system. BACKGROUND: Inflammation plays an important role in the initiation and progression of atherosclerosis, and the fibrinolytic system may prevent local thrombus formation. METHODS: We included 50 patients six months after their first myocardial infarction. Plasma levels of the inflammatory marker C-reactive protein (CRP) were determined at basal conditions, and the fibrinolytic parameters tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) were measured at basal conditions and after a standardized venous occlusion (VO) of the forearm. RESULTS: Patients with high CRP levels (> or =3 mg/l) showed a significantly higher t-PA activity at baseline compared with patients with medium (1 to 2.9 mg/l) and low (<1 mg/l) CRP levels (p <0.005). In contrast, patients with low CRP levels showed a higher increase of t-PA activity (p <0.05) and a higher reduction of PAI-1 activity during VO (p <0.05) compared with patients with medium and high CRP levels. A multivariate analysis that included cardiovascular risk factors and medical treatment showed that CRP is an independent predictor of the t-PA response after a standardized VO. CONCLUSIONS: Chronic low-grade inflammation is associated with enhanced activation of endogenous fibrinolysis at baseline but a reduced fibrinolytic response to VO. This impaired endogenous fibrinolytic capacity might be an important contributor to the increased coronary event rate associated with elevated CRP levels.

Outcome and functional capacity after prolonged intensive care unit stay.

BACKGROUND: An important proportion of critically ill patients who survives their acute illness remains in a critical state requiring intensive care management for weeks to months. Nevertheless, data on risk factors for in-hospital mortality and especially for long-term mortality and functional capacity are scarce. This study investigated outcome and prognostic factors in long-term critically ill patients. METHODS: This retrospective observational cohort study was performed at our mixed adult 8-bed cardiologic ICU at a 2200-bed University Hospital. Patient data from our local database connected to an Austrian multicenter program for quality assurance in intensive care were analyzed. Data were collected between March 1(st), 1998 and December 31(st), 2003. Patients with an ICU stay > or =30 days formed the long-term study group. Morbidity and functional capacity were assessed using the Barthel mobility index in telephone interviews. RESULTS: Patients spending > or =30 days in the ICU numbered 135 (10%) and occupied 5962 bed-days, representing 40.9% of the total bed-days. Compared with patients with an ICU stay <30 days, patients in the long-term group had a significantly higher SAPS II score during the first 24 hours after ICU admission (54 [IQR 41-65] vs. 38 [IQR 27-56], p < 0.001). There was a trend towards male preponderance in the long-term group (98/135 [82.6%] vs. 782/1215 [64.4%], p = 0.05). Differences in ICU and in-hospital mortality were not significant (28/135 (20.7%) vs. 295/1215 (24.3%), p = 0.620 and 46/135 [34.1%] vs. 360/1215 [29.6%], p = 0.285, respectively). After 12 and 48 months, the overall cumulative rates of death in hospital survivors were 14% and 26%, respectively in the short-term ICU group and 31% and 61% in the long-term group. A log-rank test revealed a significantly higher probability of survival in the short-term group after hospital discharge (log rank = 34.3, p < 0.001). Multivariate analysis of hospital survivors and non-survivors in the long-term group showed that the need for renal replacement therapy during the ICU stay was the sole independent predictor for in-hospital death and death within 1 year after ICU discharge (OR = 2.88; 95%CI 1.12-7.41, p = 0.028 and OR = 3.66, 95%CI 1.36-9.83, p = 0.01, respectively). In 28/31 long-term survivors (90%) in the long-term ICU group, the Barthel index indicated no or only moderate disability during daily activities. CONCLUSION: Hospital mortality rates in critically ill patients with a stay <30 or > or =30 days were comparable. The necessity for renal replacement therapy was the sole independent predictor for in-hospital and 1-year mortality in long-term ICU patients. Critically ill patients with a stay > or =30 days have a high and ongoing risk of death after hospital discharge; however, a substantial number of these patients are long-term survivors with no or only moderate disability during daily activities.

The adaptive immune system and long-term outcome in patients with stable coronary disease. Predictive value of routine laboratory measurements.

Components of the adaptive immune system, in particular lymphocytes and immunoglobulin, play a major role in advanced atherosclerotic lesions. We sought to determine whether routine, measurements of the relative number of circulating lymphocytes (%L) and gamma-globulin (%G) reflecting immunoglobulin are related to event-free survival in patients with stable coronary artery disease (CAD). We prospectively studied the combined endpoint all-cause mortality, myocardial infarction and coronary revascularization procedures in 141 patients after successful percutaneous coronary intervention during a median follow-up time of 13.2 years. Using Cox regression, we found a significant influence of %L on event-free survival (P=0.007) with a relative risk of 2.21 comparing third to first tertile. Subjects with higher %G values likewise had a shorter event-free survival (P=0.008) with a relative risk of 1.67 comparing third to first tertile. The predictive value of %L and %G remained significant after adjustment for demographic data, cardiovascular risk factors, extent of CAD and other inflammatory markers. We conclude that the fraction of gamma-globulin and in particular the relative lymphocyte cell count may serve as readily available and reliable prognostic tools for the long-term outcome in patients with stable CAD.

High-sensitivity C-reactive protein in the prediction of coronary events in patients with premature coronary artery disease.

BACKGROUND AND METHODS: Inflammation plays an important role in the initiation and progression of atherosclerosis and in the pathogenesis of acute cardiovascular events. Recent studies have indicated a possible association between C-reactive protein (CRP) and the clinical outcome of coronary artery disease (CAD). We studied prospectively in a group of 125 patients with premature CAD whether plasma levels of CRP as measured with a high-sensitivity assay predict risk for future coronary events. All patients had stable CAD at time of blood sampling but had originally been seen with unstable angina or myocardial infarction. The mean follow-up time after blood collection was 54 months, and death, myocardial infarction, need for coronary revascularization, or admission to hospital with angina pectoris were defined as clinical end points. RESULTS: Patients in the highest tertile of CRP levels had a >3.8-fold risk (risk ratio 3.82, 95% CI 1.19-12.17) for death, myocardial infarction, or need for coronary revascularization compared with the patients in the first tertile. The relative risk for patients in the second tertile was 3.5-fold higher (95% CI 1.04-11.56). CRP levels in the third tertile independently predicted risk after adjustment for lipids and other clinical risk factors. CONCLUSION: In patients with clinically stable conditions who have a positive history for acute coronary syndromes before age 50 years, plasma levels of CRP higher than 1.6 mg/L are predictors of future coronary events and therefore indicate the role of underlying chronic inflammation for the clinical course of CAD. Accordingly, reference limits for prediction of risk in CAD have to be lower in this specific patient group than in middle-aged or elderly patients.

Circulating t-PA antigen predicts major adverse coronary events in patients with stable coronary artery disease--a 13-year follow-up.

Thrombus formation after rupture of an atherosclerotic plaque plays a crucial role in coronary artery disease (CAD). A decreased endogenous fibrinolytic system and prothrombotic factors are supposed to influence coronary thrombosis. It was our aim to investigate the predictive value of tissue plasminogen activator (t-PA) antigen, von Willebrand Factor, Lipoprotein (a) and anti-cardiolipin antibodies for major adverse coronary events in patients with stable CAD in a prospective cohort study of more than 10 years. We observed 141 patients with angiographically proven CAD for a median follow-up period of 13 years. t-PA antigen was the only marker predicting coronary events (logistic regression, p = 0.044) with a poor prognosis for patients in the 5th quintile with an odds ratio of 7.3 (compared to the 1st quintile). The odds ratio even increased to 10.0 for coronary events associated with the "natural course" of CAD excluding events due to restenosis. t-PA antigen had a slightly higher prognostic power (ROC curve; AUC = 0.69) than fasting glucose (AUC = 0.68) and cholesterol (AUC = 0.67). Triglycerides influenced plasma levels of t-PA antigen (regression, p < 0.001). The predictive value of t-PA antigen remained significant after adjustment for inflammation (logistic regression, p = 0.013) and extent of CAD (p = 0.045) but disappeared adjusting for insulin resistance (p = 0.12). In conclusion t-PA antigen predicted coronary events during a very long-term follow-up with a comparable prognostic power to established cardiovascular risk factors. Markers of insulin resistance influenced t-PA antigen and its predictive value.

Short versus prolonged bed rest after uncomplicated acute myocardial infarction: a systematic review and meta-analysis.

BACKGROUND: Recently updated guidelines by the American College of Cardiology/American Heart Association and the European Society of Cardiology recommend at least 12 hours bed rest in patients with uncomplicated myocardial infarction. METHODS: We performed a systematic literature review and meta-analysis of randomized and quasi-randomized controlled trials comparing short versus prolonged bed rest in patients with uncomplicated acute myocardial infarction. RESULTS: We found 15 trials with 1332 patients assigned to a short period of bed rest (range 2 to 12 days) and 1326 patients assigned to prolonged bed rest (range 5 to 28 days). Generally, the studies were outdated and seemed to be of poor methodologic reporting quality. There was no evidence that shorter bed rest was more harmful than longer bed rest in terms of death, reinfarction, post-infarction angina, or thromboembolic events. CONCLUSION: We concluded that bed rest ranging from 2 to 12 days seems to be as safe as longer periods of bed rest.

Acute chest pain-a stepwise approach, the challenge of the correct clinical diagnosis.

STUDY OBJECTIVE: To assess the safety and the accuracy of a 4 h stepwise diagnostic approach relying on clinical judgement in unselected patients with acute chest pain. DESIGN: Prospective cohort study. SETTING: Emergency department (ED) of a tertiary care university hospital. PATIENTS: 1288 unselected patients presenting with acute chest pain. INTERVENTIONS: After history and physical examination, clinical judgement (step I), governed the need for further patient evaluation: baseline 12 lead electrocardiogramm (ECG) and laboratory examinations (step II), serial 12 lead ECG and laboratory examinations after 4 h (step III), and 4 h troponin T measurement (step IV) to exclude or to confirm a coronary origin of chest pain. Patients were followed clinically for 6 months for future occurrence of cardiac events (myocardial infarction, percutaneous transluminal coronary angioplasty (PTCA), CABG, cardiac death), any death and for accuracy of the ED diagnosis in non-coronary chest pain patients. MEASUREMENTS AND RESULTS: Chest pain was diagnosed to be coronary in origin in 381 and non-coronary in 907 patients, respectively. Cardiac events occurred during follow up in 240 (19%) of 1288 patients, in 233 of 381 (61%) with presumed coronary and seven of 907 (1%) with presumed non-coronary chest pain. Sensitivity, specificity, positive predictive value and negative predictive value for correct detection of coronary chest pain were 97, 86, 61 and 99%, respectively. In non-coronary chest pain patients the agreement between the ED diagnosis and the final diagnosis was good (kappa=0.71, 95% confidence interval (CI) 0.67-0.75). CONCLUSIONS: The 4 h stepwise approach guided by clinical judgement was safe for ruling out impending cardiac events in unselected patients with acute chest pain. However, more extensive evaluation is necessary for accurate rule-in of coronary chest pain.

Pre-existing anticardiolipin antibodies and development of restenosis after coronary balloon angioplasty: predictive value for a complicated course?

Immune mechanisms play a critical role in cardiovascular disease. Cardiolipins are candidate autoantigens with a prothrombotic activity of their corresponding antibodies. We investigated the influence of pre-existing immunoglobulin (Ig)M and IgG anticardiolipin (aCL) antibodies on restenosis after coronary balloon angioplasty and their interaction with tissue plasminogen activator, plasminogen activator inhibitor type-1, von Willebrand factor and lipoprotein (a) in 132 patients with stable angina pectoris using immunoassays. Thirty percent of patients developed angiographically proven restenosis estimated by three independent experienced angiographers; 12% of all patients developed recurrent restenoses at the same site during a follow-up period of 2 years. Circulating IgM aCL antibodies categorized by quartiles predicted recurrent restenoses (logistic regression, for trend P < 0.04) with an increase of relative risk (RR) per quartile of 2.09. The predictive value of IgM aCL antibodies was unchanged adjusting for established cardiovascular risk factors (P = 0.028, RR = 2.69), extent of coronary artery disease (P = 0.014, RR = 2.73) and inflammatory parameters (P = 0.025, RR = 2.79), but lost significance adjusting for other prothrombotic parameters (P = 0.24, RR = 1.76). IgM aCL antibodies positively correlated with lipoprotein (a) (r = 0.23, P = 0.04). However, there was no significant interaction between their influences on recurrent restenoses. The other prothrombotic parameters did not predict single or recurrent restenoses. In conclusion, IgM aCL antibodies may help to identify a group of patients at high risk for recurrent restenoses after coronary balloon angioplasty.

Clinical signs of pulmonary congestion predict outcome in patients with acute chest pain.

BACKGROUND: Pulmonary congestion is associated with poor outcome in patients with acute coronary syndromes. In consecutive patients presenting with acute unexplained chest pain to a primary care facility, the prognostic impact of pulmonary congestion is indeterminate. Therefore, we assessed the predictive value of clinical signs of pulmonary congestion in patients presenting with acute chest pain to an emergency department with regard to the origin of the symptoms. METHODS: 1288 consecutive patients with acute chest pain were prospectively assessed for clinical signs of pulmonary congestion. The diagnosis was confirmed by chest radiography. The association of pulmonary congestion and short- and intermediate-term mortality in patients with coronary (n = 381) and non-coronary (n = 907) causes of chest pain was determined using multivariate Cox regression analysis. RESULTS: 108 (8%) patients had clinical signs of pulmonary congestion. Within the mean follow-up period of 23 months (SD 4) 67 patients died, mainly within the first 6 months. Of 108 patients with pulmonary congestion, 82 (76%) had coronary and 26 (24%) had non-coronary chest pain. Pulmonary congestion was independently associated with mortality in patients with coronary chest pain (hazard ratio 6.4, 95% confidence interval 2.5 to 16.1, p < 0.0001), both in patients with acute coronary syndromes or angina pectoris. However, in patients with non-coronary chest pain we observed no independent association of pulmonary congestion with outcome. CONCLUSION: Clinical signs of pulmonary congestion indicate an increased risk for poor outcome in patients with chest pain due to myocardial ischemia. Mortality of these patients is high, particularly in the first months after presentation. Therefore, hospital admission is warranted, including patients with angina pectoris, who otherwise may be candidates for early discharge.

Acute chest pain--identification of patients at low risk for coronary events. The impact of symptoms, medical history and risk factors.

BACKGROUND: The evaluation of patients with acute chest pain remains challenging, as it implies the risk of fatal misdiagnosis. It is well recognized that typical angina does not specifically identify patients at high risk. We investigated the predictive value of characteristics atypical for myocardial ischemia for exclusion of acute or subacute coronary events, focusing on patients' symptoms, medical history and risk factors. METHODS: We prospectively studied 1288 consecutive patients presenting with acute chest pain at a non-trauma emergency department. Patients' symptoms, history and risk factors were evaluated using seven predefined criteria and assigned as typical or atypical for ischemic coronary chest pain. Positive predictive value (PPV) and 95% confidence intervals (95% CI) were calculated to predict or exclude acute myocardial infarction (AMI) and major adverse cardiac events (MACE: cardiovascular death, percutaneous coronary interventions, bypass surgery, or myocardial infarction) within six months. RESULTS: AMI occurred in 168 patients (13%), and 6-months MACE (including AMI) overall in 240 patients (19%). Presence of four or more criteria typical for myocardial ischemia was associated with a PPV of 0.21 (0.17 to 0.25) for predicting AMI and 0.30 (0.25 to 0.35) for 6-months MACE. Presence of four or more criteria atypical for coronary ischemia was associated with a PPV of 0.94 (0.91 to 0.96) for excluding AMI and 0.93 (0.90 to 0.96) for excluding 6-months MACE. In 165 of 476 patients under 40 years of age (35%), four or more atypical criteria excluded AMI and 6-months MACE with PPVs of 0.98 (0.96 to 1.0). CONCLUSION: Evaluation of criteria atypical for myocardial ischemia with acute chest pain may help to identify candidates for early discharge, whereas typical characteristics have very little diagnostic value.

Arterial puncture closing devices compared with standard manual compression after cardiac catheterization: systematic review and meta-analysis.

CONTEXT: Arterial puncture closing devices (APCDs) were developed to replace standard compression at the puncture site and to shorten bed rest following percutaneous coronary intervention. OBJECTIVE: To assess the safety and efficacy of APCDs (Angioseal, Vasoseal, Duett, Perclose, Techstar, Prostar) compared with standard manual compression in patients undergoing coronary angiography or percutaneous vascular interventions. DATA SOURCES: A systematic literature search of MEDLINE (1966-January 2003), EMBASE (1989-January 2003), PASCAL (1996-January 2003), BIOSIS (1990-January 2003), and CINHAL (1982-January 2003) databases and the Cochrane Central Register of Controlled Trials for relevant articles in any language. STUDY SELECTION: Included randomized controlled trials reporting vascular complications at the puncture site (hematoma, bleeding, arteriovenous fistula, pseudoaneurysm) and efficacy (time to hemostasis, time to ambulation, time to discharge from hospital). DATA EXTRACTION: Two reviewers abstracted the data independently and in duplicate. Disagreements were resolved by discussion among at least 3 reviewers. The most important criteria were adequacy of allocation concealment, whether the analysis was according to the intention-to-treat principle, and if person assessing the outcome was blinded to intervention group. Random-effects models were used to pool the data. DATA SYNTHESIS: Thirty trials met the selection criteria and included up to 4000 patients. When comparing any APCD with standard compression, the relative risk (RR) of groin hematoma was 1.14 (95% confidence interval [CI], 0.86-1.51; P =.35); bleeding, 1.48 (95% CI, 0.88-2.48; P =.14); developing an arteriovenous fistula, 0.83 (95% CI, 0.23-2.94; P =.77); and developing a pseudoaneurysm at the puncture site, 1.19 (95% CI, 0.75-1.88; P =.46). Time to hemostasis was shorter in the group with APCD compared with standard compression (mean difference, 17 minutes; range, 14-19 minutes), but there was a high degree of heterogeneity among studies. Only 2 studies explicitly reported allocation concealment, blinded outcome assessment, and intention-to-treat analysis. When limiting analyses to only trials that used explicit intention-to-treat approaches, APCDs were associated with a higher risk of hematoma (RR, 1.89; 95% CI, 1.13-3.15) and a higher risk of pseudoaneurysm (RR, 5.40; 95% CI, 1.21-24.5). CONCLUSIONS: Based on this meta-analysis of 30 randomized trials, many of poor methodological quality, there is only marginal evidence that APCDs are effective and there is reason for concern that these devices may increase the risk of hematoma and pseudoaneurysm.

Right ventricular load at exercise is a cause of persistent exercise limitation in patients with normal resting pulmonary vascular resistance after pulmonary endarterectomy.

BACKGROUND: Pulmonary endarterectomy (PEA) provides a potential cure for patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, successfully operated patients can continue to suffer from a limitation of exercise capacity, despite normalization of pulmonary vascular resistance (PVR). The purpose of the present study was to explore the cardiopulmonary exercise test (CPET) profile and the pulmonary hemodynamic response to exercise in these patients. METHODS: Thirteen successfully operated patients with CTEPH and persistent dyspnea and control subjects underwent a CPET and a right-sided heart catheterization at rest and during exercise. RESULTS: The CPET profile of the patients was characterized by mild hyperventilation and decreased peak oxygen uptake (VO2). While there were no differences in resting hemodynamics between patients and control subjects, PVR was higher in the patients after 10 min of exercise (111 ± 46 dynes/s/cm(5) vs 71 ± 42 dynes/s/cm(5), P = .04), and pulmonary arterial compliance (Ca) was lower (5.5 ± 2.3 mL/mm Hg vs 8.1 ± 3.5 mL/mm Hg, P = .048). Ca under exercise correlated with peak VO2 in the patients (R(2) = 0.825, P = .022). CONCLUSIONS: After successful PEA, patients with persistent exertional dyspnea display an abnormal pulmonary hemodynamic response to exercise, characterized by increased PVR and decreased Ca. Decreased Ca under exercise is a strong predictor of limited exercise capacity in these patients.

Impact of hypoxic hepatitis on mortality in the intensive care unit.

PURPOSE: Hypoxic hepatitis (HH) is a form of hepatic injury following arterial hypoxemia, ischemia, and passive congestion of the liver. We investigated the incidence and the prognostic implications of HH in the medical intensive care unit (ICU). METHODS: A total of 1,066 consecutive ICU admissions at three medical ICUs of a university hospital were included in this prospective cohort study. All patients were screened prospectively for the presence of HH according to established criteria. Independent risk factors of mortality in this cohort of critically ill patients were identified by a multivariate Poisson regression model. RESULTS: A total of 118 admissions (11%) had HH during their ICU stay. These patients had different baseline characteristics, longer median ICU stay (8 vs. 6 days, p < 0.001), and decreased ICU survival (43 vs. 83%, p < 0.001). The crude mortality rate ratio of admissions with HH was 4.62 (95% CI 3.63-5.86, p < 0.001). Regression analysis demonstrated strong mortality risk for admissions with HH requiring vasopressor therapy (adjusted rate ratio 4.91; 95% CI 2.51-9.60, p < 0.001), whereas HH was not significantly associated with mortality in admissions without vasopressor therapy (adjusted rate ratio 1.79, 95% CI 0.52-6.23, p = 0.359). CONCLUSIONS: Hypoxic hepatitis (HH) occurs frequently in the medical ICU. The presence of HH is a strong risk factor for mortality in the ICU in patients requiring vasopressor therapy.