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Biomedical subjects

William C Little

Publications and source records attributed to William C Little.

At least 19 recordsLinked to original sources
PubMed2006

Contribution of right-sided heart enlargement to cardiomegaly on chest roentgenogram in diastolic and systolic heart failure.

We investigated the contribution of a dilated right-sided heart to roentgenographic cardiomegaly in patients with heart failure (HF) and a normal ejection fraction (EF; diastolic HF) and those with HF and a decreased EF (systolic HF). We compared the cardiothoracic ratio (CTR) on upright chest roentgenograms and major- and minor-axis dimensions of the 4 cardiac chambers on echocardiograms in patients with HF and a normal EF (> or =0.50, n = 35) and those with a decreased EF (<0.50, n = 37) and examined the correlation between the CTR and cardiac chamber dimensions. The CTR did not differ between patients with normal and decreased EF values (0.58 +/- 0.07 vs 0.60 +/- 0.06, p = 0.26). Left-side cardiac chamber dimensions were substantially smaller in patients with a normal EF than in those with a decreased EF (left ventricular minor-axis dimension, 4.4 +/- 0.7 vs 5.8 +/- 0.8 cm, p <0.001). In contrast, right-side cardiac chamber dimensions were generally similar between groups. The CTR correlated with major-axis dimensions of the right ventricle and right atrium (p <0.01 for the 2 comparisons), but not with the left-side cardiac chamber dimensions (all p values >0.05). In conclusion, the CTR predominantly reflects right- rather than left-sided heart size in patients with HF. Right-sided heart size is similar between patients with normal and decreased EF values. Thus, despite the substantial difference in left ventricular size and EF, there is substantial overlap in the CTR between patients with diastolic and systolic HFs and the CTR is unable to discriminate between groups.

Case-Control Studies↗
PubMed2006

Development and validation of a risk score for predicting death in Chagas' heart disease.

BACKGROUND: Chagas' disease is an important health problem in Latin America, and cardiac involvement is associated with substantial morbidity and mortality. We developed a model to predict the risk of death in patients with Chagas' heart disease. METHODS: We retrospectively evaluated 424 outpatients from a regional Brazilian cohort. The association of potential risk factors with death was tested by Cox proportional-hazards analysis, and a risk score was created. The model was validated in 153 patients from a separate community hospital. RESULTS: During a mean follow-up of 7.9 years, 130 patients in the development cohort died. Six independent prognostic factors were identified, and each was assigned a number of points proportional to its regression coefficient: New York Heart Association class III or IV (5 points), evidence of cardiomegaly on radiography (5 points), left ventricular systolic dysfunction on echocardiography (3 points), nonsustained ventricular tachycardia on 24-hour Holter monitoring (3 points), low QRS voltage on electrocardiography (2 points), and male sex (2 points). We calculated risk scores for each patient and defined three risk groups: low risk (0 to 6 points), intermediate risk (7 to 11 points), and high risk (12 to 20 points). In the development cohort, the 10-year mortality rates for these three groups were 10 percent, 44 percent, and 84 percent, respectively. In the validation cohort, the corresponding mortality rates were 9 percent, 37 percent, and 85 percent. The C statistic for the point system was 0.84 in the development cohort and 0.81 in the validation cohort. CONCLUSIONS: A simple risk score was developed to predict death in Chagas' heart disease and was validated in an independent cohort.

Adult↗
PubMed2006

Angiotensin II type 1 receptor blockade prevents alcoholic cardiomyopathy.

BACKGROUND: Activation of the renin-angiotensin system (RAS) may contribute to the development of alcoholic cardiomyopathy. We evaluated the effect of angiotensin II (Ang II) type 1 receptor (AT1) blockade on the development of alcoholic cardiomyopathy. METHODS AND RESULTS: We serially evaluated left ventricular (LV) and cardiomyocyte function and the RAS over 6 months in 3 groups of instrumented dogs. Eight animals received alcohol (once per day orally, providing 33% of total daily caloric intake); 6 received alcohol and irbesartan (5 mg.kg(-1).d(-1) PO); and 8 were controls. Compared with controls, alcohol ingestion caused sustained RAS activation with progressive increases in plasma levels of Ang II, renin activity, LV angiotensin-converting enzyme activity, and LV myocyte Ang II AT(1) receptor expression. The RAS activation was followed by a progressive fall in LV contractility (E(ES), alcohol-fed dogs 3.9+/-0.8 versus control dogs 8.1+/-1.0 mm Hg/mL); reductions in the peak velocity of myocyte shortening (78.9+/-5.1 versus 153.9+/-6.2 microm/s) and relengthening; and decreased peak systolic Ca2+ transient ([Ca2+]iT) and L-type Ca2+ current (I(Ca,L); P<0.05). Irbesartan prevented the alcohol-induced decreases in LV and myocyte contraction, relaxation, peak [Ca2+]iT, and I(Ca,L). With alcohol plus irbesartan, plasma Ang II, cardiac angiotensin-converting enzyme activity, and AT1 remained close to control values. CONCLUSIONS: Chronic alcohol consumption produces RAS activation followed by progressive cardiac dysfunction. The cardiac dysfunction is prevented by AT1 receptor blockade.

Alcoholism↗
PubMed2006

Effect of losartan and hydrochlorothiazide on exercise tolerance in exertional hypertension and left ventricular diastolic dysfunction.

A randomized, double-blind study of 6 months of losartan 50 mg or hydrochlorothiazide (HCTZ) 12.5 mg was performed in 40 subjects with left ventricular diastolic dysfunction (mitral flow velocity E/A ratio < 1), exercise systolic blood pressure (BP) > 200 mm Hg, systolic BP at rest < 150 mm Hg, ejection fraction > 50%, and no ischemia. Before treatment, exercise systolic BP was 213 +/- 13 mm Hg (mean +/- SD) in the 19 patients randomized to losartan and 209 +/- 11 mm Hg in the 21 patients who received HCTZ. After 6 months, exercise systolic BP was similarly reduced in patients who received losartan (197 +/- 23 mm Hg, p < 0.01) and HCTZ (191 +/- 11 mm Hg, p < 0.01). With losartan, treadmill exercise time increased from 894 +/- 216 to 951 +/- 225 seconds (p = 0.011), and quality of life improved from 15 +/- 12 to 7 +/- 10 (p = 0.015) without a change in oxygen consumption (1,895 +/- 470 to 1,954 +/- 539 ml/min, p = 0.30). With HCTZ, exercise time (842 +/- 225 to 872 +/- 239 seconds, p = 0.32) and quality of life (19 +/- 21 vs 19 +/- 24, p = 0.43) did not change, whereas oxygen consumption decreased from 2,144 +/- 788 to 1,960 +/- 706 ml/min (p = 0.022). In conclusion, in patients with diastolic dysfunction and hypertensive responses to exercise, 6 months of losartan and HCTZ blunted systolic BP during exercise. Only losartan increased exercise tolerance and improved quality of life.

Antihypertensive Agents↗
PubMed2006

Diastolic heart failure can be diagnosed by comprehensive two-dimensional and Doppler echocardiography.

There are many myocardial and non-myocardial conditions that cause heart failure with normal left ventricular ejection fraction (LVEF). Among them, diastolic heart failure (heart failure due to diastolic dysfunction) is the most common cause of heart failure with normal LVEF. Diastolic heart failure easily can be diagnosed by comprehensive two-dimensional and Doppler echocardiography, which can demonstrate abnormal myocardial relaxation, decreased compliance, and increased filling pressure in the setting of normal LV dimensions and preserved LVEF. Therefore, diastolic heart failure should always be considered when LVEF is normal on two-dimensional echocardiography in patients with clinical evidence of heart failure. The diagnosis can be confirmed if Doppler echocardiography and myocardial tissue imaging provide evidence for impaired myocardial relaxation (i.e., decreased longitudinal velocity of the mitral annulus during early diastole and decreased propagation velocity mitral inflow), decreased compliance (shortened mitral A-wave duration and mitral deceleration time), and increased filling pressure (shortened isovolumic relaxation time and an increased ratio between early diastolic mitral and mitral annular velocities). Early identification of diastolic dysfunction in asymptomatic patients by the use of echocardiography may provide an opportunity to manage the underlying etiology to prevent progression to diastolic heart failure.

Blood Flow Velocity↗
PubMed2006

Propensity score analysis of vascular complications after diagnostic cardiac catheterization and percutaneous coronary intervention 1998-2003.

OBJECTIVES: To evaluate the adjusted risk of vascular complications after manual compression and vascular closure devices for femoral artery access site management in a large contemporary cohort, using propensity score analysis. BACKGROUND: Vascular closure devices (VCD) allow early ambulation after cardiac procedures involving femoral artery access, but whether the benefit of use of vascular closure devices (VCD) is offset by reduced safety in contemporary practice remains uncertain. METHODS: Twenty one thousand eight hundred and forty one consecutive diagnostic cardiac catheterization (n = 13,124) and percutaneous coronary intervention procedures (n = 8,717) performed via a femoral access at a single site (WFUBMC) between 1998 and 2003 were evaluated. VCD's were used based on operator preference. Propensity to receive a vascular closure device (VCD) was calculated. The relative incidence of vascular complications was evaluated by logistic regression models, using the propensity score as a covariate. RESULTS: Overall, the unadjusted incidence of any vascular complication was 1.3% for VCD use and 1.4% for manual compression, p = NS. The propensity score-adjusted odds ratio for any vascular complication comparing VCD (n = 8,707) to manual compression (n = 13,034) was 0.86 (0.67-1.11) for all procedures, 0.80 (0.53-1.21) for diagnostic procedure, and 0.90 (0.65-1.26) for interventional procedures. CONCLUSIONS: In this large single-center, contemporary observational study, the risk-adjusted occurrence of vascular complications following VCD use for femoral artery access management is not increased by VCD use. Thus, in the current era, the benefit of VCD use is not offset by reduced safety.

Aged↗
PubMed2006

Vascular complications with newer generations of angioseal vascular closure devices.

OBJECTIVES: To evaluate the safety and efficacy of newer generations of a single vascular closure device (VCD), Angioseal, compared to contemporaneous manual compression. BACKGROUND: Previous assessment of VCD safety and efficacy has been based primarily on outcomes associated with the original VCD. Few data exist comparing safety and efficacy of modifications of the original VCDs. METHODS: We evaluated in-hospital outcomes of patients undergoing diagnostic cath and percutaneous coronary intervention at a single center: 3,898 with manual compression and 3,898 with the Angioseal VCD. Three generations of the Angioseal device were studied: Generation 1, 7/97-4/00; Generation 2, 5/00-6/02; and Generation 3, 7/02-12/03. Propensity analysis was used to match patients within each generation for clinical and procedural covariates. RESULTS: Closure success was 98.5% for Generation 1, 98.6% for Generation 2, and 98.1% for Generation 3, P = NS. The odds ratio for any vascular complication comparing Angioseal to manual compression was 0.92 (0.42-2.01) for Generation 1; 0.83 (0.49-1.41) for Generation 2; and 0.75 (0.32-1.77) for Generation 3. Multivariate logistic regression identified closure success and Angioseal device Generation 3 versus Generation 1 as predictive of reduced vascular complications during the entire study period. CONCLUSION: These data indicate that the newest generation of the Angioseal VCD is at least as effective as the original device. Moreover, use of the Angioseal VCD was associated with vascular complications similar to or lower than vascular complications following manual compression for each generation of Angioseal device analyzed.

Angioplasty, Balloon, Coronary↗
PubMed2006

PCI with and without abciximab after upstream eptifibatide use: outcomes in high-risk patients.

BACKGROUND: Abciximab is often used to treat high-risk patients during percutaneous coronary intervention (PCI). Recent data indicate, however, that upstream and postprocedural treatment with low-dose glycoprotein (GP) IIb/IIIa inhibitors may be more beneficial than abciximab during and after PCI. Whether abciximab can be used safely or effectively during PCI for high-risk patients after upstream treatment with eptifibatide in patients with acute coronary syndromes (ACS) is not known. METHODS: Clinical outcomes were evaluated in 289 patients with ACS who had upstream treatment with eptifibatide, and abciximab (EA) during PCI, and compared to 560 ACS patients who had both upstream and interventional treatment with eptifibatide (EE). RESULTS: Bleeding and vascular complications of the two groups were similar. Overall, 1-year major adverse cardiac event (MACE) rates were similar: 26.0% in the EA group and 25.2% in the EE group; p = 0.82. In patients with unstable angina, the hazard of MACE at 1 year was higher with EA than EE, 1.98 (1.23-3.18), due to significantly higher rates of repeat revascularization in the EA group. In patients with myocardial infarction (MI), the hazard of MI or death at 1 year was lower in the EA than the EE group, 0.50 (0.27-0.93). CONCLUSION: In this single-center observational study, the use of abciximab for PCI after upstream use of eptifibatide for ACS was safe. Abciximab was of no benefit in patients with unstable angina, but was associated with lower MI or death in patients with MI. These observations are consistent with recent findings indicating that abciximab is of benefit in patients with NSTEMI, but not lower-risk patients.

Abciximab↗
PubMed2005

Development of a cryogen-free concentration system for measurements of volatile organic compounds.

An innovative cryogen-free concentrator system for measurement of atmospheric trace gases at the parts per trillion level has been developed with detection by routinely used gas chromatographic methods. The first-generation system was capable of reaching a trapping temperature of -186 degrees C, while the current version can reach -195 degrees C. A Kleemenko cooler is used to create liquid nitrogen equivalent trapping conditions and eliminate the use of solid absorbents, a potential source of artifacts. The method utilizes dual-stage trapping with individual cold regions. The two stages are cooled to -20 and -175 degrees C for water management and sample enrichment, respectively. Both stages house a Silonite-coated stainless steel sample loop; the second stage loop is filled with 1-mm-diameter glass beads, which provide an inert surface area for analyte concentration. In our application, the complete system employed four channels utilizing two flame ionization detectors, one electron capture detector, and a mass spectrometer. The system was automated for unattended operation and was deployed off the New England east coast on Appledore Island to measure a suite of ambient non-methane hydrocarbons, halocarbons, alkyl nitrates, and oxygenated volatile organic compounds during the International Consortium for Atmospheric Research on Transport and Transformation field campaign in summer 2004. This robust system quantified 98 ambient volatile organic compounds with precisions ranging from 0.3 to 15%.

Journal Article↗
PubMed2005

Late outcomes after intervention of vein grafts in diabetics with abciximab use.

OBJECTIVES: We sought to evaluate late clinical outcomes following elective percutaneous coronary interventions for saphenous vein graft with planned abciximab use in diabetics. BACKGROUND: Diabetes adversely affects long-term outcomes after percutaneous coronary intervention including percutaneous coronary intervention of saphenous vein grafts. Glycoprotein IIb/IIIa inhibitors reduce adverse outcomes of native vessel percutaneous coronary intervention in diabetics; however, their effects in diabetic patients undergoing percutaneous coronary interventions of saphenous vein grafts is not known. METHODS: We evaluated 509 elective percutaneous coronary interventions of saphenous vein grafts. Glycoprotein IIb/IIIa inhibitors were used in 99% of the percutaneous coronary interventions. Distal protection devices were not used. Clinical follow-up (mean 30+/-20 months) was available in 369/397 (93%). RESULTS: Overall, procedural success rate was 97% and was similar for diabetics and non-diabetics. Procedural major adverse cardiac events occurred in 4.8% diabetics, and 4.1% non-diabetics (p = NS). Late outcomes were similar for diabetics and non-diabetics with major adverse cardiac event rates of 57.6%, and 54.9%, respectively, p=NS. Multivariate logistic regression identified graft age and the presence of thrombus as predictors of increased late major adverse cardiac events. CONCLUSIONS: Following routine use of abciximab, late outcomes after percutaneous coronary interventions of saphenous vein grafts were similar for diabetics and non-diabetics suggesting that the historically observed adverse effect of diabetes on late outcomes after percutaneous coronary interventions of saphenous vein grafts may be attenuated by glycoprotein IIb/IIIa use. Selective use of glycoprotein IIb/IIIa inhibitor should be considered for diabetics undergoing percutaneous coronary interventions of saphenous vein grafts.

Abciximab↗
PubMed2005

Usefulness of an elevated B-type natriuretic peptide in predicting survival in patients with aortic stenosis treated without surgery.

Patients with aortic stenosis (AS) may remain asymptomatic with good prognoses for many years but have poor prognoses once they develop symptoms. Because the presence of symptoms is subjective, B-type natriuretic peptide (BNP) may provide a more objective indication of the prognoses of patients with AS. We evaluated 124 patients with AS (valve area <1.2 cm(2)) with clinical evaluation, Doppler echocardiography, and BNP assessment and obtained up to 2 years of follow-up without valve replacement. Patients with syncope, angina, and/or heart failure were considered to have symptoms. The 24 patients without symptoms had lower BNP levels (187 +/- 193 pg/ml) than the 100 patients with symptoms (930 +/- 928 pg/ml, p <0.001). BNP indicated symptom status, with an area under the receiver-operating characteristic curve of 0.87 (p <0.001). The optimal discrimination of symptoms occurred with BNP >190 pg/ml. Survival was significantly influenced by the presence of symptoms (relative risk [RR] 7.5, p <0.01) and BNP tertile (RR 2.9, p <0.001). The 1-year mortality rate without surgery was 6% for BNP <296 pg/ml, 34% for BNP 296 to 819 pg/ml, and 60% for BNP >819 pg/ml. No patients with BNP <100 pg/ml died. The combination of BNP and symptoms provided a better prediction of survival than symptoms alone (chi-square 13.6, p <0.001). BNP significantly (RR 2.8, p <0.01) influenced survival after correction for other univariate predictors (coronary artery disease, symptoms, functional class, ejection fraction, and aortic valve area). In conclusion, elevated BNP indicates progressively worse survival in patients with AS treated medically. Thus, the measurement of BNP supplements the evaluation of symptoms in determining the prognoses of patients with AS.

Aged↗
PubMed2005

Preprocedural white blood cell count and major adverse cardiac events late after percutaneous coronary intervention in saphenous vein grafts.

Elevation of white blood cells (WBCs) is associated with worse outcomes in patients with coronary artery disease (CAD), including patients undergoing percutaneous coronary intervention (PCI) of native coronary arteries, but this relation has not been studied in patients with saphenous vein graft disease undergoing PCI. A total of 530 patients who underwent PCI of saphenous vein grafts from May 1997 to July 2002 were followed for >3 years. Major adverse coronary events (MACEs) were assessed as a composite of death, myocardial infarction, or revascularization during follow-up (mean 2.7 years). Patients with MACEs (n = 287) were younger and had more thrombotic and ostial lesions (p < 0.05) than those without MACEs (n = 243). The preprocedural WBC count was also significantly higher in the MACE group than in the non-MACE group (8.1 x 10(3)/mul, range 6.6 to 10.1, vs 7.0 x 10(3)/mul, range 5.6 to 8.2; p < 0.001). After adjusting for covariates, multiple logistic regression analysis revealed the preprocedural WBC count to be an independent predictor for MACEs (odds ratio 1.2; 95% confidence interval 1.1 to 1.3, p < 0.001). Patients in the highest quartile of the preprocedural WBC level had a significantly increased risk of MACEs (lowest vs highest quartile, 41.3% vs 72.4%; odds ratio 3.7; 95% confidence interval 2.2 to 6.3). Thus, an elevated preprocedural WBC count is associated with increased risk of MACEs in patients undergoing PCI for saphenous vein graft lesions.

Aged↗
PubMed2005

Statin therapy may be associated with lower mortality in patients with diastolic heart failure: a preliminary report.

BACKGROUND: No therapy has been shown to improve survival in heart failure (HF) with a normal ejection fraction (EF). There are plausible reasons to hypothesize that statins may be of benefit in HF with a normal EF. METHODS AND RESULTS: We evaluated 137 patients with HF and an EF > or =0.50. The effect of treatment received at study entry on survival was determined. During a follow-up of 21+/-12 months, 20 deaths were observed. Treatment with an ACE inhibitor or receptor blocker, beta-blocker, or calcium blocker had no significant effect on survival. In contrast, treatment with a statin was associated with a substantial improvement in survival (relative risk of death [95% CI] 0.22 [0.07 to 0.64]; P=0.006). Patients receiving statins had higher baseline LDL cholesterol than those not receiving statins (153+/-45 versus 98+/-33 mg/dL, P<0.01). After statin therapy, LDL cholesterol levels fell to a similar level (101+/-32 mg/dL) as in patients not receiving statins (98+/-33 mg/dL). After adjustment for differences in baseline clinical variables between groups (hypertension, diabetes, coronary artery disease, and serum creatinine), statin therapy was associated with lower mortality (adjusted relative risk of death [95% CI] 0.20 [0.06 to 0.62]; P=0.005). Similarly, after propensity matching, statin therapy was associated with improved survival (log-rank 6.12; P=0.013) and a trend toward improved survival without cardiovascular hospitalization (log-rank 3.02; P=0.082). CONCLUSIONS: Statin therapy may be associated with improved survival in patients with HF and a normal EF.

Adult↗
PubMed2005

Contribution of left ventricular diastolic dysfunction to heart failure regardless of ejection fraction.

Heart failure (HF) has been classified as systolic and diastolic based on the left ventricular ejection fraction. We hypothesized that left ventricular diastolic dysfunction is an important element of HF regardless of ejection fraction. Two hundred six patients who had clinical HF were compared with 72 age-matched controls. Diastolic dysfunction, as assessed by the mitral filling pattern and tissue Doppler imaging, was present in >90% of patients who had HF regardless of ejection fraction and was more frequent and severe than in age-matched controls (p <0.001). In patients who had HF, B-type natriuretic peptide correlated with diastolic dysfunction (r = 0.62, p <0.001) but not with ejection fraction or end-diastolic volume index (EDVI). The degree of diastolic dysfunction influenced survival rate (risk ratio 1.64, p <0.05), whereas ejection fraction and EDVI did not. Systolic function measured by systolic mitral annular velocity was decreased in patients who had HF and an ejection fraction </=0.40 (4.8 +/- 1.1 cm/s) and, to a lesser extent, an ejection fraction >/=0.50 (6.6 +/- 1.8 cm/s) compared with control subjects (8.0 +/- 2.1 cm/s, p <0.01). Patients who had HF and an ejection fraction >/=0.50 had an increased ratio of ventricular mass to EDVI. Patients who had HF and an ejection fraction </=0.40 had increased left ventricular EDVI. Thus, regardless of ejection fraction, patients who have HF also have diastolic dysfunction. Diastolic dysfunction is a better predictor of B-type natriuretic peptide levels and mortality than ejection fraction or left ventricular EDVI. In addition to diastolic dysfunction, HF with an ejection fraction >/=0.50 is associated with mild systolic dysfunction and an increased ratio of left ventricular mass to EDVI. In HF with an ejection fraction </=0.40, systolic dysfunction and left ventricular dilation accompany diastolic dysfunction.

Aged↗
PubMed2005

Effect of the transmural extent of myocardial scar on left ventricular systolic wall thickening during intravenous dobutamine administration.

Using magnetic resonance imaging, the extent of scar tissue due to chronic infarction and quantification of dobutamine systolic wall thickening (SWT) can be measured simultaneously in human subjects. To determine whether the transmural extent of scar tissue determines dobutamine SWT in chronic ischemic heart disease, we assessed the transmural extent of hyperenhancement and dobutamine SWT with magnetic resonance imaging in 16 patients. The transmural extent of hyperenhancement correlated inversely with dobutamine SWT (r = -0.7, p <0.001). All segments with dobutamine SWT >/=2 mm showed a transmural extent of hyperenhancement of <50%.

Aged↗