Pericardial and pleural effusions in congestive heart failure-anatomical, pathophysiologic, and clinical considerations.

Transudative pleural and pericardial effusions are not uncommon in patients with congestive heart failure. Pericardial effusion forms only with elevation of the right-sided filling pressure in the heart. In patients with biventricular failure, there is no evidence that elevated left-sided pressure, in the absence of elevated right-sided pressure, can cause a pericardial effusion. Pleural effusion forms with acute elevation of the right-sided or the left-sided filling pressure in the heart. In patients with congestive heart failure, elevated right-sided filling pressures are less common than elevated left-sided filling pressures, thus, explaining a lower prevalence of pericardial than pleural effusions. Pleural effusions in patients with congestive heart failure are typically bilateral. However, a unilateral pleural effusion is more commonly seen on the right side. Although multiple theories attempt to explain the right-sided preponderance of pleural effusion, to date, no mechanism has been universally accepted or experimentally proven.

Retrospective determination of the area at risk for reperfused acute myocardial infarction with T2-weighted cardiac magnetic resonance imaging: histopathological and displacement encoding with stimulated echoes (DENSE) functional validations.

BACKGROUND: The aim of this study was to determine whether edema imaging by T2-weighted cardiac magnetic resonance (CMR) imaging could retrospectively delineate the area at risk in reperfused myocardial infarction. We hypothesized that the size of the area at risk during a transient occlusion would be similar to the T2-weighted hyperintense region observed 2 days later, that the T2-weighted hyperintense myocardium would show partial functional recovery after 2 months, and that the T2 abnormality would resolve over 2 months. METHODS AND RESULTS: Seventeen dogs underwent a 90-minute coronary artery occlusion, followed by reperfusion. The area at risk, as measured with microspheres (9 animals), was comparable to the size of the hyperintense zone on T2-weighted images 2 days later (43.4+/-3.3% versus 43.0+/-3.4% of the left ventricle; P=NS), and the 2 measures correlated (R=0.84). The infarcted zone was significantly smaller (23.1+/-3.7; both P<0.001). To test whether the hyperintense myocardium would exhibit partial functional recovery over time, 8 animals were imaged on day 2 and 2 months later. Systolic strain was mapped with displacement encoding with stimulated echoes. Edema, as detected by a hyperintense zone on T2-weighted images, resolved, and regional radial systolic strain partially improved from 4.9+/-0.7 to 13.1+/-1.5 (P=0.001) over 2 months. CONCLUSIONS: These findings are consistent with the premise that the T2 abnormality depicts the area at risk, a zone of reversibly and irreversibly injured myocardium associated with reperfused subendocardial infarctions. The persistence of postischemic edema allows T2-weighted CMR to delineate the area at risk 2 days after reperfused myocardial infarction.

Quantitative myocardial infarction on delayed enhancement MRI. Part I: Animal validation of an automated feature analysis and combined thresholding infarct sizing algorithm.

PURPOSE: To develop a computer algorithm to measure myocardial infarct size in gadolinium-enhanced magnetic resonance (MR) imaging and to validate this method using a canine histopathological reference. MATERIALS AND METHODS: Delayed enhancement MR was performed in 11 dogs with myocardial infarction (MI) determined by triphenyltetrazolium chloride (TTC). Infarct size on in vivo and ex vivo images was measured by a computer algorithm based on automated feature analysis and combined thresholding (FACT). For comparison, infarct size by human manual contouring and simple intensity thresholding (based on two standard deviation [2SD] and full width at half maximum [FWHM]) were studied. RESULTS: Both in vivo and ex vivo MR infarct size measured by the FACT algorithm correlated well with TTC (R = 0.95-0.97) and showed no significant bias on Bland Altman analysis (P = not significant). Despite similar correlations (R = 0.91-0.97), human manual contouring overestimated in vivo MR infarct size by 5.4% of the left ventricular (LV) area (equivalent to 55.1% of the MI area) vs. TTC (P < 0.001). Infarct size measured by simple intensity thresholdings was less accurate than the proposed algorithm (P < 0.001 and P = 0.007). CONCLUSION: The FACT algorithm accurately measured MI size on delayed enhancement MR imaging in vivo and ex vivo. The FACT algorithm was also more accurate than human manual contouring and simple intensity thresholding approaches.

Determining canine myocardial area at risk with manganese-enhanced MR imaging.

PURPOSE: To test whether manganese-enhanced magnetic resonance (MR) imaging can safely depict the myocardial area at risk both during coronary artery occlusion and for at least 2 hours after reperfusion in dogs. MATERIALS AND METHODS: All procedures were performed in accordance with the animal care and use committee of the National Institutes of Health. In eight dogs, the left anterior descending (LAD) coronary artery was occluded for 90 minutes, and 15 micromol of MnCl2 per kilogram of body weight was intravenously infused for 12 minutes. Phase-sensitive inversion-recovery MR imaging of the LAD arterial territory was performed before occlusion, during MnCl2 infusion, and for at least 2 hours after reperfusion. Hemodynamic responses were monitored continuously. Fluorescent microsphere enhancement was used as the reference standard for determining the area at risk ex vivo. Results are reported as percentages of left ventricular area. Correlation, Bland-Altman, and t test analyses were performed. RESULTS: Significant differences in manganese-induced contrast enhancement of the area at risk, the normal myocardium, and the blood (P < .01) were measured during LAD artery occlusion and at least 2 hours after reperfusion. No significant changes in heart rate or blood pressure were detected during or after MnCl2 infusion. Measurements of the area at risk obtained with manganese-enhanced MR imaging during LAD artery occlusion and 2 hours after reperfusion correlated well with the size of the at-risk area demarcated by the fluorescent microspheres (during occlusion: y = 0.81x, R = 0.90; during reperfusion: y = 0.83x, R = 0.89). Bland-Altman analysis revealed small systematic errors in measurements at both occlusion and reperfusion. CONCLUSION: Manganese-enhanced MR imaging can depict the area at risk during LAD artery occlusion and at least 2 hours after reperfusion without hemodynamic compromise.

Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model.

CONTEXT: Recent studies have suggested a link between inhaled particulate matter exposure in urban areas and susceptibility to cardiovascular events; however, the precise mechanisms remain to be determined. OBJECTIVE: To test the hypothesis that subchronic exposure to environmentally relevant particulate matter, even at low concentrations, potentiates atherosclerosis and alters vasomotor tone in a susceptible disease model. DESIGN, SETTING, AND PARTICIPANTS: Between July 21, 2004, and January 12, 2005, 28 apolipoprotein E-/- (apoE-/-) mice were, based on randomized assignments, fed with normal chow or high-fat chow and exposed to concentrated ambient particles of less than 2.5 microm (PM2.5) or filtered air (FA) in Tuxedo, NY, for 6 hours per day, 5 days per week for a total of 6 months. MAIN OUTCOME MEASURES: Composite atherosclerotic plaque in the thoracic and abdominal aorta and vasomotor tone changes. RESULTS: In the high-fat chow group, the mean (SD) composite plaque area of PM2.5 vs FA was 41.5% (9.8%) vs 26.2% (8.6%), respectively (P<.001); and in the normal chow group, the composite plaque area was 19.2% (13.1%) vs 13.2% (8.1%), respectively (P = .15). Lipid content in the aortic arch measured by oil red-O staining revealed a 1.5-fold increase in mice fed the high-fat chow and exposed to PM2.5 vs FA (30.0 [8.2] vs 20.0 [7.0]; 95% confidence interval [CI], 1.21-1.83; P = .02). Vasoconstrictor responses to phenylephrine and serotonin challenge in the thoracic aorta of mice fed high-fat chow and exposed to PM2.5 were exaggerated compared with exposure to FA (mean [SE], 134.2% [5.2%] vs 100.9% [2.9%], for phenylephrine, and 156.0% [5.6%] vs 125.1% [7.5%], for serotonin; both P = .03); relaxation to the endothelium-dependent agonist acetylcholine was attenuated (mean [SE] of half-maximal dose for dilation, 8.9 [0.2] x 10(-8) vs 4.3 [0.1] x 10(-8), respectively; P = .04). Mice fed high-fat chow and exposed to PM2.5 demonstrated marked increases in macrophage infiltration, expression of the inducible isoform of nitric oxide synthase, increased generation of reactive oxygen species, and greater immunostaining for the protein nitration product 3-nitrotyrosine (all P<.001). CONCLUSION: In an apoE-/- mouse model, long-term exposure to low concentration of PM2.5 altered vasomotor tone, induced vascular inflammation, and potentiated atherosclerosis.

Patent foramen ovale: anatomy versus pathophysiology--which determines stroke risk?

This study investigated anatomic and pathophysiologic variables that may determine which patent foramen ovale (PFO) are associated with cerebrovascular accidents (CVAs). Anatomic features of a PFO have been identified as risk factors that predispose certain people to cryptogenic strokes (strokes of unknown cause). However, potential pathophysiologic variables that can determine the pressure gradient between left and right atria, which could influence the right-to-left shunt through a PFO, have not been examined. A retrospective study included 78 consecutive patients in whom PFOs were detected during routine transesophageal echocardiography examination. Group I included 36 patients with CVAs of unknown cause (cryptogenic stroke). Group II included 42 patients without CVAs whose PFOs were incidental findings. Anatomic features measured included separation and overlap between septum primum and septum secundum, interatrial septal motion, and the relative size of the right-to-left shunt with peripheral saline solution contrast injections. Pathophysiologic variables considered were those that could cause elevated left atrial pressure, thereby minimizing the right-to-left shunt.Patients with a clinical neurologic event (group I) had a larger right-to-left shunt volume of contrast bubbles than did patients with asymptomatic PFO (group II; P =.004). The size of the overlap between septum primum and septum secundum was less in patients from group I as compared with patients from group II (7.5 +/- 3.4 mm versus 9.9 +/- 6.0 mm; P =.026). However, other anatomic features of PFO that are determinants of the "opening" were not significantly different between the 2 groups. No statistically significant difference was found in the distance of the separation between septum primum and septum secundum (2.5 +/- 2.0 mm versus 1.9 +/- 1.6 mm; P = not significant). The prevalence of interatrial septal aneurysm was also similar between the 2 groups (28% versus 21%; P = not significant). However, the prevalence of variables that could potentially raise left atrial pressure was greater in patients without CVA as compared with those with a CVA (48% versus 14%; P =.01). In our study, anatomic features alone did not determine interatrial shunt size and pathophysiologic variables that could raise left atrial pressures did differentiate between patients with a PFO with a CVA/transient ischemic attack and those without it. Thus, both anatomic and pathophysiologic mechanisms should be considered in determination of the potential clinical significance of a PFO.