P. Aylward

Randomized, Double-blind Comparison of Hirulog Versus Heparin in Patients Receiving Streptokinase and Aspirin for Acute Myocardial Infarction (HERO)

Background Thrombolytic therapy improves survival after myocardial infarction through reperfusion of the infarct-related artery. Thrombin generated during thrombolytic administration may reduce the efficacy of thrombolysis. A direct thrombin inhibitor may improve early patency rates. Methods and Results Four hundred twelve patients presenting within 12 hours with ST-segment elevation were given aspirin and streptokinase and randomized in a double-blind manner to receive up to 60 hours of either heparin (5000 U bolus followed by 1000 to 1200 U/h), low-dose hirulog (0.125 mg/kg bolus followed by 0.25 mg · kg−1 · h−1 for 12 hours then 0.125 mg · kg−1 · h−1), or high-dose hirulog (0.25 mg/kg bolus followed by 0.5 mg · kg−1 · h−1 for 12 hours then 0.25 mg · kg−1 · h−1). The primary outcome was Thrombolysis In Myocardial Infarction trial (TIMI) grade 3 flow of the infarct-related artery at 90 to 120 minutes. TIMI 3 flow was 35% (95% CI, 28% to 44%) with heparin, 46% (95% CI, 38% to 55%) with low-dose hirulog, a...

Prolonged alveolocapillary barrier damage after acute cardiogenic pulmonary edema

ObjectivesTo determine whether acute cardiogenic pulmonary edema is associated with damage to the alveolocapillary barrier, as evidenced by increased leakage of surfactant specific proteins into the circulation, to document the duration of alveolocapillary barrier damage in this setting, and to explore the role of pulmonary parenchymal inflammation by determining if circulating tumor necrosis factor-&agr; is increased after acute cardiogenic pulmonary edema. DesignProspective, observational study. SettingCritical care, cardiac intensive care, and cardiology wards of a tertiary-care university teaching hospital. PatientsA total of 28 patients presenting with acute cardiogenic pulmonary edema and 13 age-matched normal volunteers. InterventionsCirculating surfactant protein-A and -B and tumor necrosis factor-&agr; were measured on days 0 (presentation), 1, 3, 7, and 14. Clinical markers of pulmonary edema were documented at the same times. Measurements and Main ResultsSurfactant protein-A and -B were elevated on day 0 compared with controls (367 ± 17 ng/mL vs. 303 ± 17 and 3821 ± 266 ng/mL vs. 2747 ± 157 [mean ± sem], p < .05), and although clinical, hemodynamic and radiographic variables improved rapidly (p < .001), surfactant protein-A and -B rose further until day 3 (437 ± 22, p < .001, 4642 ± 353, p < .01). Tumor necrosis factor-&agr; was elevated at presentation (p < .05), doubled by day 1 (6.98 ± 1.36 pg/mL, p < .05), remained elevated on day 3 (5.72 ± 0.96 pg/mL, p < .05), and peak levels were related to chest radiograph extravascular lung water score (rp = 0.64, p = .003). ConclusionsAlthough the initial increase in plasma surfactant protein-A and -B may represent hydrostatic stress failure of the alveolocapillary barrier, the prolonged elevation, when hemodynamic abnormalities have resolved, and the delayed elevation of tumor necrosis factor-&agr; are consistent with pulmonary parenchymal inflammation, which may further damage the alveolocapillary barrier. This prolonged physiologic defect at the alveolocapillary barrier after acute cardiogenic pulmonary edema may partly account for the vulnerability of these patients to recurrent pulmonary fluid accumulation.

Plasma surfactant protein-B: a novel biomarker in chronic heart failure

Background—In chronic heart failure (CHF), elevated pulmonary microvascular pressure (Pmv) results in pulmonary edema. Because elevated Pmv may alter the integrity of the alveolocapillary barrier, allowing leakage of surfactant protein-B (SP-B) from the alveoli into the circulation, we aimed to determine plasma levels of SP-B in CHF and their relation to clinical status. Methods and Results—Fifty-three outpatients with CHF had plasma SP-B and N-terminal proBNP (NT-proBNP) assayed, in addition to a formalized clinical assessment at each clinic review over a period of 18 months. The control group comprised 19 normal volunteers. Plasma SP-B was elevated in CHF (P<0.001), and levels increased with New York Heart Association classification (P<0.001). SP-B correlated with objective clinical status parameters and NT-proBNP. During follow-up, major cardiovascular events occurred in patients with higher plasma SP-B (P<0.01) and NT-proBNP (P<0.05). Furthermore, on conditional logistic regression analysis, only SP-B was independently associated with CHF hospitalization (P=0.005). The 53 patients underwent a total of 210 outpatient visits. When the diuretic dosage was increased on clinical grounds, SP-B had increased 39% (P<0.001) and NT-proBNP had increased 32% (P<0.001). Conversely, at the next visit, SP-B fell 12% (P<0.001), whereas NT-proBNP fell 39% (P<0.001). Conclusions—Plasma SP-B is increased in CHF, and levels are related to clinical severity. Furthermore, within individual patients, SP-B levels vary with dynamic clinical status and NT-proBNP levels. Because plasma SP-B is independently associated with CHF hospitalization, it may, by virtue of its differing release mechanism to NT-proBNP, be a clinically useful biomarker of the pulmonary consequences of raised Pmv.

Angiographic frame counts 90 minutes after streptokinase predict left ventricular function at 48 hours following myocardial infarction.

Objective To assess whether the 90 minute corrected thrombolysis in myocardial infarction frame count (CTFC) in the infarct related artery predicts left ventricular function at 48 hours in patients with myocardial infarction treated with aspirin, streptokinase, and either heparin or Hirulog. Design and setting Analysis of 251 patients with acute myocardial infarction enrolled in the international, multicentre Hirulog early reperfusion/occlusion (HERO-1) trial, who underwent both 90 minute coronary angiography and 48 hour left ventriculography. Main outcome variables The CTFC was determined in the infarct related artery 90 minutes after starting intravenous streptokinase (1.5 × 106 U over 30 to 60 minutes), and compared with indices of left ventricular function assessed by contrast ventriculography at 48 hours. Results A CTFC of ⩽u200927 frames (previously reported mean + 2 SD in coronary arteries of patients without acute infarction) occurred in 29% of infarct related arteries, and was associated with a lower infarct zone mean chord score (−2.06 v −2.54, pu2009=u20090.01), a lower fraction of chords >u20092 SD below normal (37%v 51%, pu2009=u20090.005), and trends towards higher left ventricular ejection fractions (60.9%v 58.2%, pu2009=u20090.11) and lower end systolic volumes (50.1 ml v 55.9 ml, pu2009=u20090.23). A CTFC of ⩽u200940 at 90 minutes occurred in 50% of infarct related arteries, and was associated with a significantly lower mean chord score (−2.20 v −2.60, pu2009=u20090.02), a smaller fraction of chords >u20092 SD below normal (41%v 52%, pu2009=u20090.025), a smaller end systolic volume (49.1 ml v 59.3 ml, pu2009=u20090.02), and a higher left ventricular ejection fraction (60.4%v 56.5%, pu2009=u20090.03). Conclusions The 90 minute CTFC predicts left ventricular function at 48 hours following streptokinase. The CTFC associated with better ventricular function may be higher than values determined from a non-infarct population.

CIRCULATING SURFACTANT PROTEIN-B LEVELS INCREASE ACUTELY IN RESPONSE TO EXERCISE-INDUCED LEFT VENTRICULAR DYSFUNCTION

1.u2002As a result of its enormous surface area and necessary thinness for gas exchange, the alveolocapillary barrier is vulnerable to mechanical disruption from raised pulmonary microvascular pressure (Pmv).