Real-Time Deduction of Mechanisms and Kinetics Underlying Photocatalytic Water Disinfection: Cell Motility and Particle Tracking.

The current methods used to study photocatalysis-assisted water disinfection at a laboratory scale may not lead to process scale-up for large-scale implementation. These methods do not capture the process complexity and address all the factors underlying disinfection kinetics, including the physical characteristics (e.g., shape and size) of the photocatalyst, the light intensity, the form of the catalyst (e.g., free-floating and immobilized), and the photocatalyst-microorganism interaction mode (e.g., collision mode and constant contact mode). This drawback can be overcome using in situ methods to track the interaction between the photocatalysts and the microorganisms (e.g., Escherichia coli) and thereby engineering the resulting disinfection kinetics. Contextually, this study employed microscopy and particle-tracking algorithms to quantify in situ cell motility of E. coli undergoing titanium dioxide (TiO2) nanowire-assisted photocatalysis, which was observed to correlate with cell viability closely. This experimentation also informed that the E. coli bacterium interacted with the photocatalysts through collisions (without sustained contact), which allowed for phenomenological modeling of the observed first-order kinetics of E. coli inactivation. Addition of fluorescent-tagging assays to microscopy revealed that cell membrane integrity loss is the primary mode of bacterial inactivation. This methodology is independent of the microorganism or the photocatalyst type and hence is expected to be beneficial for engineering disinfection kinetics.

Coronary revascularization strategy for ST elevation myocardial infarction with multivessel disease: experience and results at 1-year follow-up.

Primary percutaneous coronary intervention (PCI) of culprit lesions (CLs) is the standard of care in patients presenting with ST elevation myocardial infarction (STEMI). However, optimal revascularization strategy for significant nonculprit lesions (non-CLs) in the setting of STEMI remains controversial. The importance of defining of such a strategy lies in the fact that approximately 50% of patients with STEMI have multivessel disease (MVD). The aim of this study was to describe characteristics, therapeutic strategies, and 1-year outcomes in a cohort of patients with STEMI and MVD. We retrospectively analyzed a cohort of 63 patients with STEMI and MVD obtained from a 5-year catheterization database. MVD was defined as ≥70% stenosis of ≥2 epicardial coronary arteries. This cohort was followed for a period of 1 year for major adverse cardiac events (MACE was defined as acute coronary syndrome, new onset heart failure, or death) and all-cause mortality. PCI with stent placement was the major therapeutic procedure (87.5%) performed for CLs. Non-CLs did not undergo interventions in a majority of individuals (47.6%), while the remaining patients underwent PCI (29%) and coronary artery bypass graft surgery (22%) for non-CLs. At 1-year follow-up, prevalence of MACE events and death in the entire cohort were 30% and 15%, respectively. A trend for better outcomes (1-year cumulative MACE events but not mortality) was observed in CL-only intervention cohort compared with non-CL intervention. The PCI and Coronary artery bypass graft surgery cohorts did not show any significant difference in clinical outcomes. In this retrospective cohort of patients with MVD who presented with STEMI, no intervention of noncritical lesions was the prevalent approach, reflecting guideline recommendations. CL-only intervention strategy showed a better clinical outcome than non-CL intervention. Intervention of noncritical lesions therefore did not seem to improve MACEs or all-cause mortality at 1-year of follow-up and might in fact have had a detrimental effect on outcomes.

Predictors of residual cardiovascular risk in patients on statin therapy for primary prevention.

BACKGROUND: Low-density lipoprotein cholesterol-lowering therapy is an important aspect of primary prevention of cardiovascular disease (CVD). Statins are the most widely used drug therapy for achieving low-density lipoprotein goals based on an individual's 10-year risk. However, substantial risk of CVD events still exists even when a person is on statins. We sought to explore the predictors of future CVD events in individuals on statins with no pre-existing CVD. METHODS: The analysis was done on subjects who were on statins (n = 919) at baseline in the Multi-Ethnic Study of Atherosclerosis limited access dataset from the National Heart, Lung and Blood Institute. The primary outcome variable was all-cause CVD events (n = 67). Multivariate regression Cox proportional hazard analysis was done to identify potential independent predictors of all-cause CVD. RESULTS: Our cohort consisted of 47% males, with a mean age of 66 ± 9 years. Sixty-seven participants (7.3%) experienced CVD events during a mean follow-up of 4.4 years. A higher coronary artery calcium score, homocysteine levels, waist circumference and a lower large arterial elasticity index were identified as independent predictors of CVD events. CONCLUSION: Homocysteine, waist circumference, coronary artery calcification and the large artery elasticity index appear to be the major independent predictors of CVD events in individuals on statins with no pre-existing CVD. In addition to emphasizing weight loss, alternative approaches beyond lipid reduction may need to be explored to better characterize and attenuate the residual risk in subjects on statin therapy for primary prevention.

Relationship between red cell distribution width and microalbuminuria: a population-based study of multiethnic representative US adults.

INTRODUCTION: Microalbuminuria (MA), a renal marker of vascular injury, is an independent predictor of cardiovascular (CV) events. Red cell distribution width (RDW), an emerging CV risk predictor, has not been evaluated for its association with MA. METHODS: We evaluated 8,499 participants of the National Health and Nutrition Examination Survey (NHANES) 1999-2006, where RDW was evaluated as a continuous variable and in quartiles (Q(1) ≤ 12.1, Q(2) 12.2-12.5, Q(3) 12.6-13 and Q(4) >13). Multivariate adjusted logistic regression analysis was performed to estimate the odds of having MA (n = 1,736; adjusted for traditional CV risk factors, race, BMI, estimated glomerular filtration rate, hemoglobin, mean corpuscular volume, high-sensitivity C-reactive protein and nutritional factors deficiencies of iron, folate and vitamin B(12)). RESULTS: The prevalence of MA increased with increasing RDW (13.52% in Q(1) vs. 30.02% in Q(4), p < 0.001). The odds of having MA for those in Q(4) was 2.49 (95% CI: 1.95-3.18, p < 0.001) compared to those in Q(1) after the adjustments. No effect modification was observed by covariates on the association between RDW and MA. CONCLUSION: Elevated RDW is independently associated with a higher risk of MA. An interaction between chronic inflammation, oxidative stress, neurohumoral overactivity and endothelial dysfunction may explain this association and the attendant elevated CV/renal risk.

Global and regional left ventricular contractile impairment in patients with wolff-Parkinson-white syndrome.

BACKGROUND: To assess regional systolic function and global contractile function in patients with WPW Syndrome. METHOD: Eleven cases with manifest Wolff-Parkinson-White (WPW) syndrome in sinus rhythm were compared to 11 age matched controls. 2D strain analysis was performed and peak segmental radial strain (pRS) values obtained from basal ventricular parasternal short-axis images (70 +/- 5 frames/sec) using a dedicated software package. Heterogeneity of radial strain pattern in six circumferential basal left ventricular segments was measured in terms of standard deviations of peak RS (SD(pRS)) or range (difference between maximum and minimum peak RS i.e. Range(pRS)). Spectral Doppler (continuous wave) measurements were acquired through the left ventricular outflow tract to determine Pre Ejection Period (PEP), Left Ventricular Ejection Time (LVET) and measures of left ventricular systolic performance. RESULTS: LV segmental radial strain was profoundly heterogeneous in WPW cases in contrast to fairly homogenous strain pattern in normal subjects. Wide SD(pRS) values 17.5 +/- 8.9 vs 3.3 +/- 1.4, p<0.001 and Range(pRS) 42.7 +/- 20.8 vs.8.5 +/- 3.6 , p<0.001 were observed among WPW and healthy subjects respectively. PEP (132.4 +/- 14.7 vs 4.7 +/- 0.5ms, p<0.001) and corrected PEP (76.1 +/- 8.0 vs 2.7 +/- 0.4ms, p<0.001) were significantly longer in WPW patients compared to controls. The PEP/LVET ratio was also significantly greater in WPW cohort (0.49 +/- 0.04 vs. 0.28 +/- 0.05, p <0.001) suggesting global systolic dysfunction. CONCLUSIONS: Patients with manifest preexcitation (predominantly those with right-sided pathways) have regional and global contractile dysfunction resulting from aberrant impulse propagation inherent to the preexcited state.

Comparison of five-year outcome in African Americans versus Caucasians following percutaneous coronary intervention.

BACKGROUND: Studies regarding short-term outcomes after percutaneous coronary intervention (PCI) have reported no ethnic differences and data on long-term follow-up is conflicting and sparse. METHODS: 730 consecutive patients (67% African American) undergoing PCI from January 1999 to December 2000 at a tertiary care center in Detroit, MI, were followed up. End points studied included either all cause mortality collected from Social Security Death Index or first hospital admission after the index procedure due to myocardial infarction(MI), congestive heart failure(CHF), and revascularization (PCI or coronary artery bypass graft surgery). RESULTS: African-Americans undergoing PCI had significant differences in baseline cardiovascular co-morbidity and were more likely to present with acute myocardial infarction than Caucasians. On Kaplan Meier survival analysis and log rank test, each ethnic group had equivalent survival for cumulative end points upto 6-month follow-up, however longer follow-up to 5 year was characterized by lower survival rate in African Americans compared to Caucasians (41% vs. 54%, log rank P 0.01). After adjustment for potential confounders, AA ethnicity (Adjusted HR 1.62, 95% CI 1.01-1.28, P 0.04) remained a predictor of adverse cardiac outcome (Death/MI/CHF) at five-year follow-up (Cox regression propensity adjusted hazard analysis). CONCLUSIONS: African American patients undergoing PCI had unfavorable baseline cardiovascular characteristics but comparable short-term outcome compared to whites. However, at 5-year follow-up, African Americans had worse clinical outcome, higher incidence of acute myocardial infarction, congestive heart failure and significantly lower long-term survival.

Ethnic and sex differences in disease burden in patients undergoing coronary angiography: the confounding influence of obesity.

BACKGROUND: Data from cohort studies, predominantly in Caucasians, have identified obesity as a major risk factor for coronary artery disease (CAD), irrespective of sex. In contrast, reports examining the effects of obesity on mortality in African Americans suggest a weak relationship between body mass index (BMI) and mortality, particularly among women. Data correlating body weight with angiographic severity of CAD is sparse in minority populations. We sought to investigate ethnic-sex differences in the influence of obesity on the extent and severity of CAD. METHODS: We studied 640 patients (66.9% African American) who underwent coronary angiography at a tertiary care center. Cardiovascular risk factor profiles and CAD burden, quantified by the Duke Myocardial Jeopardy scoring system, a validated prognostication tool, were compared across ethnic and sex groups. RESULTS: Clustering of major cardiovascular risk factors, a higher prevalence of obesity classes II and III, and a statistically significant inverse correlation between BMI and Duke scores were observed among the cohort of African American women. General linear model analysis and stepwise multiple linear regression analysis revealed Duke score to be negatively associated with BMI and higher classes of obesity after adjustment for age and other cardiovascular risk factors in African American women but not in other subgroups. CONCLUSIONS: The observed inverse relationship between BMI and angiographic severity of CAD in African American women is novel and appears to support prior data on the weak association between BMI and cardiovascular mortality in this subgroup.

Determinants of amount of contrast utilized in patients undergoing percutaneous coronary procedures.

OBJECTIVE: To determine predictors of contrast amount during coronary angiography and percutaneous coronary intervention. BACKGROUND: Contrast-induced nephropathy is a leading cause of hospital-acquired acute renal insufficiency. During percutaneous coronary procedures, contrast amount is a major risk factor incriminated in development of contrast-induced nephropathy. METHODS: Demographic and procedural details were obtained for consecutive patients undergoing percutaneous coronary procedures between January 2002 and October 2005 (N=962, mean+/-standard error of contrast amount: 216.6+/-3.0 ml) at a tertiary care hospital. RESULTS: A significant difference (P value <0.05) in unadjusted mean contrast volume was observed between subgroups of percutaneous coronary intervention vs. coronary angiography, patients with a history of coronary artery bypass grafting, patients undergoing additional procedures and multivessel and multisite percutaneous coronary interventions. On General Linear Model analysis, independent predictors (beta coefficient, 95% confidence interval, P value) of increased contrast amount during percutaneous coronary procedures were history of coronary artery bypass grafting (44.4, 30.6-58.2, <0.001), type of coronary procedure (85.2, 73.4-97.0, <0.001 for percutaneous coronary intervention vs. coronary angiography), number of interventions and number of additional procedures performed. Among additional procedures, rotablation, intravascular ultrasound and Angiojet were associated with increased contrast use. No significant independent effect on the contrast amount was observed with percutaneous coronary intervention location (right coronary artery vs. left anterior descending artery vs. circumflex artery) site (ostial vs. proximal vs. mid vs. distal) of percutaneous coronary intervention or with interventions on chronic total occlusions on the contrast amount. CONCLUSION: Data from our study could guide the coronary angiographer in moderating the volume of contrast utilized as well as assist with the elective planning of complex therapeutic procedures.

Myocardial infarction with angiographically normal coronary arteries in the contemporary era.

BACKGROUND: Myocardial infarction with angiographically normal coronary arteries (MINC) is a well recognized clinical entity, but limited data regarding outcome and prognostic factors exist in the literature. This study sought to identify clinical characteristics and etiological factors as well as outcome predictors in patients with MINC. DESIGN: Retrospective follow-up study. METHODS: Fifty-eight patients presenting with MINC fulfilled the study inclusion criteria. Clinical characteristics, cardiovascular risk factors, and etiologic and laboratory data were harvested and compared with those obtained from patients with myocardial infarction and single vessel coronary artery disease (MISVD). Follow-up information regarding survival and cardiac events such as angina, reinfarction and heart failure was collected and prognostic factors identified. RESULTS: Compared with the MISVD group, MINC patients had a lower prevalence of hypercholesterolemia and ST elevation. Hypercoagulopathy, collagen tissue disorder, cocaine abuse and Takotsubo cardiomyopathy were identified etiologies in some MINC patients. During follow-up, patients with MINC were less likely to sustain reinfarction (log-rank P<0.001) and cardiovascular death (log-rank P=0.04) on Kaplan-Meier survival analysis. Recurrence of angina and heart failure were the most prevalent cardiac events in the MINC group. Cox proportional multivariate regression analysis identified left ventricular ejection fraction as an independent predictor of cardiac events in the MINC cohort. CONCLUSION: MINC is associated with lower mortality and morbidity compared with infarction in the setting of single vessel disease. Left ventricular function is an independent predictor of poor outcome.

Severity of coronary artery disease in obese patients undergoing coronary angiography: "obesity paradox" revisited.

BACKGROUND: Recent studies have highlighted the existence of an 'obesity paradox' in patients undergoing coronary angiography, i.e., a high body mass Index (BMI) is associated with less severe coronary lesions. We sought to confirm the existence of this phenomenon in the US patient population. METHODS: Study subjects included 770 consecutive patients (470 men, 428 African-Americans, 212 Caucasians) referred for coronary angiography to a tertiary care center. Duke myocardial jeopardy score, a prognostication tool predictive of 1-year mortality in coronary artery disease (CAD) patients, was assigned to angiographic data. Patients were classified according to their BMI (kg/m2) as normal (21-24), overweight (25-29), obesity class I (30-34), class II (35-39) and class III (40 or above). RESULTS: Patients in the increasing obesity class had a higher prevalence of diabetes, hypertension and dyslipidemia and were more likely to be women. A negative correlation was observed between BMI and age (R = - 0.15 p < 0.001) as well as between BMI and Duke Jeopardy score (r = - 0.07, p < 0.05) indicating that patients with higher BMI were referred for coronary angiography at a younger age, and had a lower coronary artery disease (CAD) burden. BMI was not an independent predictor of coronary lesion severity on multivariate stepwise linear regression analysis. CONCLUSION: Obese patients are referred for coronary angiography at an earlier age and have a lower CAD burden lending further credence to the existence of an apparent "obesity paradox". However, obesity per se, after adjustment for comorbidities, is not an independent predictor of severity of coronary artery disease.

Association of novel biomarkers with future cardiovascular events is influenced by ethnicity: results from a multi-ethnic cohort.

BACKGROUND: We sought to define the influence of ethnicity on associations between novel biomarkers and cardiovascular disease (CVD) events among Multi-Ethnic Study of Atherosclerosis (MESA) study participants, a community based population of asymptomatic US adults. METHODS: Baseline (log transformed) levels of biomarkers namely C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), D-dimer, plasmin-antiplasmin complex (PAP) and factor VIII were used to predict the cumulative incidence of all CVD events in an ethnicity stratified study cohort from Cox-proportional hazard analysis where models were adjusted for relevant confounders. RESULTS: Ethnic cohorts included 2362 Caucasians, 1601 African Americans, 1353 Hispanics, and 751 Chinese. At mean 4.6 years of follow-up, 286 CVD events were identified with cumulative incidence of 11.3% in Caucasians, 9.8% in African Americans, 11.3% in Hispanics and 6.9% in Chinese. Biomarker risk association with CVD events incidence was significantly influenced by ethnicity with positive association (HR, 95% CI, p value) being shown for: CRP among Caucasians only (1.23, 1.04-1.47, <0.01) IL-6 among African Americans only (1.69, 1.15-2.48, <0.01) and fibrinogen among Caucasians (3.05, 1.21-7.69, 0.02), African Americans (3.51, 1.09-11.2, 0.03) and Hispanics (4.16, 1.23-14.1, 0.02) only. None of the biomarkers were able to predict CVD in Chinese. Association between above biomarkers and CVD was bi-directional: cases with CVD events had higher mean levels of biomarkers; cases in higher quartiles of biomarkers had increased cumulative incidence of CVD events. CONCLUSION: Study results from a vast, ethnically diverse, asymptomatic US adult population suggest that biomarker association with incident CVD events is significantly influenced by ethnicity.

Two-dimensional strain profiles in patients with physiological and pathological hypertrophy and preserved left ventricular systolic function: a comparative analyses.

OBJECTIVE: This study was designed to examine the utility of two-dimensional strain (2DS) or speckle tracking imaging to typify functional adaptations of the left ventricle in variant forms of left ventricular hypertrophy (LVH). DESIGN: Cross-sectional study. SETTING: Urban tertiary care academic medical centres. PARTICIPANTS: A total of 129 subjects, 56 with hypertrophic cardiomyopathy (HCM), 34 with hypertensive left ventricular hypertrophy (H-LVH), 27 professional athletes with LVH (AT-LVH) and 12 healthy controls in sinus rhythm with preserved left ventricular systolic function. METHODS: Conventional echocardiographic and tissue Doppler examinations were performed in all study subjects. Bi-dimensional acquisitions were analysed to map longitudinal systolic strain (automated function imaging, AFI, GE Healthcare, Waukesha, Wisconsin, USA) from apical views. RESULTS: Subjects with HCM had significantly lower regional and average global peak longitudinal systolic strain (GLS-avg) compared with controls and other forms of LVH. Strain dispersion index, a measure of regional contractile heterogeneity, was higher in HCM compared with the rest of the groups. On receiver operator characteristics analysis, GLS-avg had excellent discriminatory ability to distinguish HCM from H-LVH area under curve (AUC) (0.893, p<0.001) or AT-LVH AUC (0.920, p<0.001). Tissue Doppler and LV morphological parameters were better suited to differentiate the athlete heart from HCM. CONCLUSIONS: 2DS (AFI) allows rapid characterisation of regional and global systolic function and may have the potential to differentiate HCM from variant forms of LVH.

Glycosylated hemoglobin and prevalent metabolic syndrome in nondiabetic multiethnic U.S. adults.

BACKGROUND: Metabolic syndrome poses a significant risk for cardiovascular disease. Recently, glycosylated hemoglobin (HbA1c) has been included in the diagnostic criteria for diabetes mellitus and prediabetes. We sought to determine if HbA1c is associated with prevalent metabolic syndrome in nondiabetic U.S. adults. METHODS: A total of 9,022 nondiabetic participants of National Health and Nutrition Examination Surveys 1999-2008 (age, 47.5 ± 18.3 years, 51% females) were divided into quintiles (Q) of HbA1c: Q1 (reference), ≤5%; Q2, 5.1%-5.3%; Q3, 5.4%-5.5%; Q4, 5.6%-5.7%; and Q5, ≥5.8%. Modified National Cholesterol Education Program Adult Treatment Panel III criteria were used to identify metabolic syndrome (n=2,821; 31.3%). Unadjusted and adjusted multivariate logistic regression analysis was performed to assess the risk of metabolic syndrome. RESULTS: A graded increase in odds of having prevalent metabolic syndrome with increase from each quintile of HbA1c compared to Q1 was observed after adjusting for age, sex, race, body mass index (BMI), total cholesterol, lipid-lowering therapy, current smoking, family history of diabetes, C-reactive protein, and fasting insulin. Stratified analysis based on gender, ethnicity, and BMI showed similar results. The HbA1c value of ≥5.4% remained appropriate cutoff for predicting metabolic syndrome in Caucasians and Hispanics, whereas ≥5.6% provided the best accuracy for African Americans based on receiver operating characteristics analysis. CONCLUSION: HbA1c much below the level for prediabetes was associated with prevalence of the metabolic syndrome in a cohort of nondiabetic U.S. adults. HbA1c can be considered as a surrogate marker for metabolic syndrome in nondiabetics.

Homocysteine and reclassification of cardiovascular disease risk.

OBJECTIVES: The purpose of this study was to examine whether adding homocysteine (Hcy) to a model based on traditional cardiovascular disease (CVD) risk factors improves risk classification. BACKGROUND: Data on using Hcy to reclassify individuals in various risk categories beyond traditional approaches have not been adequately scrutinized. METHODS: We performed a post hoc analysis of the MESA (Multi-Ethnic Study of Atherosclerosis) and NHANES III (National Health and Nutrition Examination Survey III) datasets. Hcy was used to predict composite CVD and hard coronary heart disease (CHD) events in the MESA study and CVD and CHD mortality in the NHANES III survey using adjusted Cox-proportional hazard analysis. Reclassification of CHD events was performed using a net reclassification improvement (NRI) index with a Framingham risk score (FRS) model with and without Hcy. RESULTS: Hcy level (>15 µmol/l) significantly predicted CVD (adjusted hazard ratio [aHR]: 1.79, 95% confidence intervals [CI]: 1.19 to 1.95; p = 0.006) and CHD events (aHR: 2.22, 95% CI: 1.20 to 4.09; p = 0.01) in the MESA trial and CVD (aHR: 2.72, 95% CI: 2.01 to 3.68; p < 0.001) and CHD mortality (aHR: 2.61, 95% CI: 1.83 to 3.73; p < 0.001) in the NHANES III, after adjustments for traditional risk factors and C-reactive protein. The level of Hcy, when added to FRS, significantly reclassified 12.9% and 18.3% of the overall and 21.2% and 19.2% of the intermediate-risk population from the MESA and NHANES cohorts, respectively. The categoryless NRI also showed significant reclassification in both MESA (NRI: 0.35, 95% CI: 0.17 to 0.53; p < 0.001) and NHANES III (NRI: 0.57, 95% CI: 0.43 to 0.71; p < 0.001) datasets. CONCLUSIONS: From these 2 disparate population cohorts, we found that addition of Hcy level to FRS significantly improved risk prediction, especially in individuals at intermediate risk for CHD events.

Red cell distribution width and risk of coronary heart disease events.

Red cell distribution width (RDW) has emerged as a powerful predictor of all-cause mortality in variety of cardiovascular settings. However, no data are available associating RDW with coronary heart disease (CHD) risk in a healthy and nationally representative multiethnic population. A total of 7,556 participants of the National Health and Nutrition Examination Surveys 1999 to 2006 (age 41.5 ± 15.8 years, 60% women) were divided into 3 categories according to their 10-year Framingham risk of hard CHD events: <10% (n = 6,173, reference category), 10% to 20% (n = 1,093, intermediate-risk category), and >20% (n = 290, high-risk category). Unadjusted and adjusted multivariate logistic regression analyses were performed evaluating RDW as a predictor of CHD risk. Each unit increase (0.1) in RDW posed a statistically significant greater odds of being in the intermediate-risk category (odds ratio -1.35, 95% confidence interval 1.27 to 1.45, p <0.001) and high-risk category (odds ratio -1.38, 95% confidence interval 1.25 to 1.53, p <0.001) compared to the reference category, after adjusting for race, body mass index, estimated glomerular filtration rate, hemoglobin A1c, C-reactive protein, hemoglobin, and mean corpuscular volume. Additional adjustments with serum iron, vitamin B(12), and folic acid levels did not affect the association. Subsequently, we divided participants into 2 categories according to their anemia status (as defined by the World Health Organization) to evaluate its effect. An RDW level greater than the seventy-fifth percentile in both anemic and nonanemic participants was a significant predictor of greater CHD risk while RDW of the seventy-fifth percentile or less in anemic participants failed to predict CHD (compared to nonanemic participants with similar RDW as the reference category). In conclusion, a higher RDW appears to be a powerful independent predictor of future CHD risk.

Traditional cardiovascular risk factors and severity of angiographic coronary artery disease in the elderly.

Over 80% of annual coronary heart disease mortality occurs in the elderly, a rapidly expanding subset of the population. The authors retrospectively examined the relationship between traditional cardiovascular risk factors and atherosclerotic coronary artery disease burden in a cohort of 631 elderly patients undergoing angiography. Age and male sex but not hypertension or dyslipidemia were predictors of presence of obstructive coronary artery disease (Duke score >or=2). Only diabetes mellitus emerged as an independent predictor of obstructive coronary artery disease burden. Smoking was found to be predictive of left main coronary artery disease. In summary, severity of angiographic disease in the elderly as assessed by Duke Myocardial Jeopardy scoring appears to correlate poorly with prevalence of established traditional cardiovascular risk factors.

Usefulness of intravenously administered fluid replenishment for detection of patent foramen ovale by transesophageal echocardiography.

Patent foramen ovale (PFO) is associated with cryptogenic stroke, migraine headache, decompression sickness, and platypnea-orthodeoxia syndrome. Patients undergoing transesophageal echocardiography are often hypovolemic from preprocedural fasting and might not demonstrate right to left shunting owing to insufficient right atrial pressure generation, despite provocative maneuvers. We hypothesized that volume replenishment with saline loading could potentially unmask a PFO by favorably modulating the interatrial pressure gradient. Our study sought to examine the role of pre- or intraprocedural intravenous fluid replenishment on PFO detection during transesophageal echocardiography. A total of 103 patients were enrolled. An initial series of bubble injections was performed unprovoked and then with provocative maneuvers such as the Valsalva maneuver and coughing. The patients were then given a rapid 500 ml saline bolus, and the same sequence of bubble injections was repeated. The presence, type, and magnitude of the right to left shunts were noted before and after the saline bolus. The detection rate of PFO increased from 10.6% to 26.2% after saline loading without any provocative maneuvers. When combined with provocative maneuvers (Valsalva or cough), saline loading improved the detection rate from 17.4% to 32.0%. Overall, from amongst the 103 enrolled patients, saline bolusing resulted in a de novo diagnosis of PFO in 15 patients, atrial septal aneurysm in 15, PFO coexisting with an atrial septal aneurysm in 10, and pulmonary arteriovenous fistula in 5 patients. In conclusion, saline infusion in appropriately selected patients during transesophageal echocardiography significantly enhances the detection of PFOs and pulmonary arteriovenous fistulas.

Spectrum of electrocardiographic and angiographic coronary artery disease findings in patients with cocaine-associated myocardial infarction.

BACKGROUND: Cocaine is the most common abused drug in patients presenting to the emergency room with chest pain and frequently leads to cardiac catheterization procedure. The extent of severity underlying coronary artery disease (CAD) in this subgroup of patients has not been well defined. This study set out to define the coronary anatomy as well as the extent of CAD in patients with cocaine-associated myocardial infarction (MI) and correlate that to the presenting electrocardiogram (ECG). METHODS: Ninety-seven consecutive patients with documented MI and positive urine drug screen for cocaine metabolites were included in the study. Demographic, clinical, ECG and coronary angiography variables were collected. RESULTS: ST elevation MI was encountered in 32% of the patients. Other ECG findings included ST segment depression, T-wave inversion, left ventricular hypertrophy, conduction blocks and/or old MI in more than 80% of cases. Of the total of 66 patients who underwent angiography, 82% had obstructive CAD, with single-vessel disease being the most frequent finding. None of these presenting ECG findings correlated with angiographic location or severity of obstructive CAD. In nearly one-fifth of the patients, troponin elevation suggestive of cardiac myonecrosis occurred in the absence of ECG findings or angiographic coronary disease. CONCLUSION: The majority of patients with cocaine-associated MI have obstructive CAD with predominant single-vessel disease. Although ECG abnormalities are frequently encountered, they are of limited diagnostic value in the clinical decision making.

VCP/p97 AAA-ATPase does not interact with the endogenous wild-type cystic fibrosis transmembrane conductance regulator.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a chloride channel that is defective in cystic fibrosis. The most common mutation, DeltaF508 CFTR, is retained in the endoplasmic reticulum, retrotranslocated into the cytosol, and degraded by the proteasome. In a proteomics screen to identify DeltaF508 CFTR interacting proteins, we found that valosin-containing protein (VCP)/p97, a Type II AAA ATPase that is a component of the retrotranslocation machinery, binds DeltaF508 CFTR, and this interaction is stabilized by proteasomal inhibition. Since wild-type (WT) CFTR has been reported to be inefficiently processed during biogenesis with as much as 75% of the newly synthesized protein degraded by the proteasome, we examined the VCP interaction in Calu-3, T-84, and 16HBE, three epithelial cell lines that endogenously express WT CFTR. The results indicate that when WT CFTR processing is efficient, as demonstrated in Calu-3 cells, VCP does not interact. Interestingly, overexpression of recombinant WT CFTR in Calu-3 cells results in inefficient processing and VCP interaction, demonstrating that CFTR processing efficiency and the VCP interaction are tightly coupled. Furthermore, induction of ER stress and activation of the unfolded protein response result in inefficient processing of WT CFTR in Calu-3 cells and promote the WT CFTR-VCP interaction. The results support the hypothesis that components of the retrotranslocation machinery such as VCP do not interact with CFTR in epithelial cells that endogenously express WT CFTR, since under normal conditions the processing of the WT protein is efficient.