SPECT gated blood pool phase analysis of lateral wall motion for prediction of CRT response

Amplitude, defined as the magnitude of contraction of the myocardium, is obtained from phase analysis but has not been investigated to the same extent as phase-based parameters for predicting the outcome of cardiac resynchronization therapy (CRT). The size of scar present in the lateral wall of the left ventricle (LV) has been shown in some studies to predict response to CRT. Scar is associated with impaired regional LV wall motion and is expected to result in a reduction in the corresponding amplitude values derived from phase analysis. Our objective was to determine the correlation between amplitude and scar, and to evaluate amplitude parameters as surrogates for scar in predicting response to CRT. 49 patients underwent a single photon emission computed tomography (SPECT) radionuclide angiography (RNA) scan as well as FDG viability and Rubidium-82 perfusion PET scans prior to undergoing CRT. Phase analysis was performed on the SPECT RNA data to extract amplitude values used to define amplitude size (AmpSize) and amplitude score (AmpScore) parameters. Scar size and scar score were obtained from the PET scans based on a 5 segment model. Scar parameters were then compared to amplitude parameters in the lateral wall for the whole population as well as both ischemic (N = 27) and non-ischemic (N = 22) populations using Pearson correlation. The ability of amplitude parameters to predict response to CRT was also investigated and compared to scar parameters. The largest ROC AUC values were obtained in the ischemic population where values of 0.67 and 0.68 were observed for lateral wall AmpSize and AmpScore respectively. Both parameters produced the same sensitivity and specificity values of 83 and 67 %. Amplitude size in the lateral wall showed significant correlation with lateral wall scar size in all patients (r = 0.51), which was further strengthened in the ischemic patient sub-group (r = 0.64). Lateral wall amplitude-based parameters obtained from SPECT RNA phase analysis produced an overall accuracy in predicting CRT response in ischemic patients that was not significantly different to that of PET lateral wall scar parameters. A significant correlation existed between amplitude size and scar size in the lateral wall.     

Particulate air pollution and vascular reactivity: the bus stop study

Objective Particulate air pollution is associated with cardiovascular morbidity but mechanisms are not well understood. We tested the effects on vascular reactivity of exposure to fine particulates matter mass (PM_2.5), number of particles ≤1 μm/m³ (PM_1.0) and nitrogen dioxide concentration (NO₂). Method About 39 healthy volunteers sat outside for 2 h at two different Ottawa bus stops. Flow-mediated vasodilation (FMD) of the brachial artery was then measured by ultrasound and expressed as: (maximum artery diameter after release of a blood pressure cuff inflated above systolic pressure—baseline resting diameter)/baseline resting diameter. Results A 30 μg/m³ increase in PM_2.5 exposure corresponded to a 0.48% reduction in FMD, P = 0.05 representing a 5% relative change in the maximum ability to dilate. Results were consistent between the two bus stops and not sensitive to type of analysis. No significant association was found between FMD and NO₂, PM_1.0 or traffic density. Conclusion PM_2.5 may reduce the capacity to vasodilate, a potential explanation for the documented association with cardiovascular morbidity.     

The utility of magnetic resonance imaging in early‐stage breast cancer survivors—An institutional experience and literature review

The role of breast magnetic resonance imaging (MRI) in the screening of breast cancer survivors with remaining breast tissue is not well studied. We sought to evaluate the outcomes of screening breast MRI in a cohort of breast cancer survivors. A population of patients with history of stage I‐IIIa breast cancer and ≥1 MRI a year or later from diagnosis between 2006‐2008 were identified using the National Comprehensive Cancer Network data base from two large Boston‐area cancer centers. Patient and disease characteristics were obtained from the data base, and medical records were reviewed to identify the index MRI (first eligible), indications, and two‐year outcomes. Overall, 647 patients had breast MRI scans during the study period including 342 eligible patients whose index MRIs were done for breast screening purposes. 47/342 (13.7%) were abnormal, and 3.8% (13/342) underwent biopsy, resulting in the detection of 3 cases of locoregional recurrence or new primary breast cancer (0.9%, 95% CI = 0.2%‐2.5%). Of 295 patients with a normal index screening MRI, 12 had a breast cancer recurrence diagnosed within 2 years (4.1% 95%CI = 2.1%‐7.0%), and 5 of these recurrences were limited to MRI‐screened breast tissue. No statistically significant difference in the rate of 2‐year locoregional or distant recurrence was observed between patients with an abnormal screening MRI and those with a normal scan. Adjunct single breast MRI surveillance in a general population of breast cancer survivors one year after diagnosis detected few recurrences, and its effect on short‐term outcomes was unclear.     

Differentiation of restrictive cardiomyopathy from pericardial constriction: assessment of diastolic function by radionuclide angiography

Diastolic filling variables were studied in 12 patients with the hemodynamic features of constriction, of whom 5 had restrictive cardiomyopathy, 5 had pericardial constriction and 2 had combined pericardial constriction and restrictive cardiomyopathy. The values were compared with those in 10 normal subjects of comparable age. The filling fractions between 10% and 70% of the diastolic time interval were greater in patients with pericardial constriction than in those with restrictive cardiomyopathy (p less than 0.01 between 20% and 50%, p less than 0.05 at 10%, 60% and 70%), with no overlap. The filling fractions in patients with pericardial constriction were also greater than those in normal subjects between 10% and 60% of the diastolic time interval. The filling fraction was lower in patients with restrictive cardiomyopathy than in normal subjects at 40% of the diastolic time interval (p less than 0.05). The time to peak filling rate in patients with pericardial constriction was shorter (110 +/- 14 ms) than in those with restrictive cardiomyopathy (195 +/- 45 ms, p less than 0.01) or in normal subjects (173 +/- 32 ms, p less than 0.01). The percent of atrial contribution to left ventricular filling was higher in those with restrictive cardiomyopathy (45 +/- 17%) than in those with pericardial constriction (21 +/- 6%, p less than 0.05) or in normal subjects (24 +/- 9%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of office, home and 24-hour ambulatory blood pressures in borderline and mild hypertension

Clinic/office (casual), home (self), and twenty-four-hour ambulatory (ABP) blood pressure determinations were compared in 32 subjects defined by conventional office criteria as mild or borderline hypertensives. Office diastolic blood pressures (mean 93.1 +/- 5.3 mmHg) were significantly higher than either home (mean 88.9 +/- 7.1 mm Hg) or awake ABP (mean 88.4 +/- 8.4 mm Hg) readings for the total group, as well as for the mild hypertension subgroup (office mean 96.0 +/- 3.5 mm Hg, home mean 91.0 +/- 8.0, awake ABP mean 90.4 +/- 8.8) but not for the borderline subgroup. In the total study group, office diastolic blood pressure (DBP) correlated better with home DBP (r = 0.58, p = 0.0005), than with the awake ABP (r = 0.40, p = 0.02). Home DBP correlated well with awake DBP (r = 0.48, p = 0.006). In subgroup analysis, office DBPs correlated well with home (self) readings for both the mild (r = 0.53, p = 0.03) and the borderline (r = 0.62, p = 0.01) subgroups. When office DBPs were compared with awake ABP DBPs, the correlation coefficient for the mild subgroup was significant (r = 0.49, p = 0.04); this was not the case for the borderline subgroup (r = 0.10, p = NS). Comparison of home (self) DBPs with awake ABP determinations revealed a good correlation for the borderline subgroup (r = 0.63, p = 0.01) but not for the mild subgroup (r = 0.35, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)     

An initial strategy of intensive medical therapy is comparable to that of coronary revascularization for suppression of scintigraphic ischemia in high-risk but stable survivors of acute myocardial infarction.

OBJECTIVES: The purpose of this study was to determine the relative benefit of intensive medical therapy compared with coronary revascularization for suppressing scintigraphic ischemia. BACKGROUND: Although medical therapies can reduce myocardial ischemia and improve patient survival after acute myocardial infarction, the relative benefit of medical therapy versus coronary revascularization for reducing ischemia is unknown. METHODS: A prospective randomized trial in 205 stable survivors of acute myocardial infarction was made to define the relative efficacy of an intensive medical therapy strategy versus coronary revascularization for suppressing scintigraphic ischemia as assessed by serial gated adenosine Tc-99m sestamibi myocardial perfusion tomography. All patients at baseline had large total (> or =20%) and ischemic (> or =10%) adenosine-induced left ventricular perfusion defects and an ejection fraction > or =35%. Imaging was performed during 1 to 10 days of hospital admission and repeated in an identical fashion after optimization of therapy. Patients randomized to either strategy had similar baseline demographic and scintigraphic characteristics. RESULTS: Both intensive medical therapy and coronary revascularization induced significant but comparable reductions in total (-16.2 +/- 10% vs. -17.8 +/- 12%; p = NS) and ischemic (-15 +/- 9% vs. -16.2 +/- 9%; p = NS) perfusion defect sizes. Likewise, a similar percentage of patients randomized to medical therapy versus coronary revascularization had suppression of adenosine-induced ischemia (80% vs. 81%; p = NS). CONCLUSIONS: Sequential adenosine sestamibi myocardial perfusion tomography can effectively monitor changes in scintigraphic ischemia after anti-ischemic medical or coronary revascularization therapy. A strategy of intensive medical therapy is comparable to coronary revascularization for suppressing ischemia in stable patients after acute infarction who have preserved LV function.     

Synovial fluid levels of complement SC5b-9 and fragment Bb are elevated in patients with rheumatoid arthritis.

To determine whether complement turnover in synovial fluids of patients with rheumatoid arthritis (RA) reflects activation by the classical or alternative pathway, we used novel immunoassays to measure products of complement activation (the membrane attack complex SC5b-9 and the cleavage fragments Bb and C4d). Mean synovial fluid levels of SC5b-9 were more than 8 times higher in RA than in crystal-induced arthritis (gout and pseudogout) and over 16 times higher than in degenerative joint disease (DJD). Similarly, Bb levels were more than 3 times higher in RA synovial fluids than in crystal-induced arthritis and over 7 times higher than in DJD. Levels of C4d did not differ among the groups. SC5b-9 levels correlated with synovial fluid C3 anaphylatoxin (C3a), Bb, and C4d levels (r = 0.81, 0.62, and 0.51, respectively). In patients with RA, synovial fluid SC5b-9 levels correlated with C3a and Bb (r = 0.6 and 0.56, respectively) but not with C4d. Therefore, novel assays for complement activation indicate that both classical and alternative pathways are involved in complement turnover and that the alternative pathway contributes more to complement activation in RA than in DJD or crystal-induced arthritis.     

Gene expression analysis in serial liver fine needle aspirates

No method with low morbidity presently exists for obtaining serial hepatic gene expression measurements in humans. While hepatic fine needle aspiration (FNA) has lower morbidity than core needle biopsy, applicability is limited due to blood contamination, which confounds quantification of gene expression changes. The aim of this study was to validate FNA for assessment of hepatic gene expression. Liver needle biopsies and FNA procedures were simultaneously performed on 17 patients with chronic hepatitis C virus infection with an additional FNA procedure 1 week later. Nine patients had mild/moderate fibrosis and eight advanced fibrosis. Gene expression profiling was performed using Affymetrix microarrays and TaqMan qPCR; pathway analysis was performed using Ingenuity. We developed a novel strategy that applies liver‐enriched normalization genes to determine the percentage of liver in the FNA sample, which enables accurate gene expression measurements overcoming biases derived from blood contamination. We obtained almost identical gene expression results (ρ = 0.99, P < 0.0001) comparing needle biopsy and FNA samples for 21 preselected genes. Gene expression results were also validated in dogs. These data suggest that liver FNA is a reliable method for serial hepatic tissue sampling with potential utility for a variety of preclinical and clinical applications.     

Differential exercise effects of captopril and nadolol in patients with essential hypertension.

In a crossover study, 12 patients with mild to moderate hypertension were given placebo, captopril (12.5 to 50 mg three times a day), and nadolol (20 to 160 mg once a day) to control the resting diastolic blood pressure to a nearly identical degree (p less than 0.0001) (106.1 +/- 4 placebo, 89.6 +/- 8 captopril, 89.8 +/- 7 nadolol). Both drugs lowered (p less than 0.0004) systolic and diastolic blood pressure at rest and during exercise. However, systolic blood pressure lowering during exercise was more pronounced (p less than 0.05) with nadolol than with captopril (difference of 6 mmHg, 16 mmHg, and 21 mmHg at 5.0, 7.0, and 9.0 metabolic equivalents (METS) respectively). Heart rate was lower (p less than 0.05) at rest and during exercise with nadolol as compared with placebo and with captopril. These data imply different mechanisms of action of the two drugs at rest and during exercise and may help in selection of drug therapy in special patient subsets.