Lori Daniels - Academia.edu (original) (raw)

Papers by Lori Daniels

Research paper thumbnail of Cardiovascular biomarkers in acute Kawasaki disease

International Journal of Cardiology, 2013

Endomycocardial biopsies have demonstrated that subclinical myocarditis is a universal feature of... more Endomycocardial biopsies have demonstrated that subclinical myocarditis is a universal feature of acute Kawasaki disease (KD). We investigated biochemical evidence of myocardial strain, oxidative stress, and cardiomyocyte injury in 55 acute KD subjects (30 with paired convalescent samples), 54 febrile control (FC), and 50 healthy control (HC) children by measuring concentrations of cardiovascular biomarkers. Levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and soluble ST2 (sST2) were elevated in acute vs. convalescent KD, FC, and HC (p≤0.002), while γ-glutamyl transferase and alanine amino transferase as measures of oxidative stress were increased in acute vs. FC (p≤0.0002). Cardiac troponin I (cTnI) levels, using a highly sensitive assay, were elevated in 30% and 40% of paired acute and convalescent KD subjects, respectively, and normalized within two years of disease onset. NT-proBNP and sST2 negatively correlated with deceleration time, but only NT-proBNP correlated with MV E:A ratio and internal diameter of the coronary arteries (RCA/LAD Zworst). NT-proBNP and sST2 were elevated in acute KD subjects and correlated with impaired myocardial relaxation. These findings, combined with elevated levels of cTnI, suggest that both cardiomyocyte stress and cell death are associated with myocardial inflammation in acute KD.

Research paper thumbnail of ACUTE MYOCARDIAL ISCHEMIA IN ADULTS SECONDARY TO MISSED KAWASAKI DISEASE IN CHILDHOOD

Journal of the American College of Cardiology, 2014

Coronary artery aneurysms that occur in 25% of untreated Kawasaki disease (KD) patients may remai... more Coronary artery aneurysms that occur in 25% of untreated Kawasaki disease (KD) patients may remain clinically silent for decades and then thrombose resulting in myocardial infarction. Although KD is now the most common cause of acquired heart disease in children in Asia, the United States, and Western Europe, the incidence of KD in Egypt is unknown. We tested the hypothesis that young adults in Egypt presenting with acute myocardial ischemia may have coronary artery lesions because of KD in childhood. We reviewed a total of 580 angiograms of patients ≤40 years presenting with symptoms of myocardial ischemia. Coronary artery aneurysms were noted in 46 patients (7.9%), of whom 9 presented with myocardial infarction. The likelihood of antecedent KD as the cause of the aneurysms was classified as definite (n = 10), probable (n = 29), or equivocal (n = 7). Compared with the definite and probable groups, the equivocal group had more traditional cardiovascular risk factors, smaller sized aneurysms, and fewer coronary arteries affected. In conclusion, in a major metropolitan center in Egypt, 6.7% of adults aged ≤40 years who underwent angiography for evaluation of possible myocardial ischemia had lesions consistent with antecedent KD. Because of the unique therapeutic challenges associated with these lesions, adult cardiologists should be aware that coronary artery aneurysms in young adults may be because of missed KD in childhood.

Research paper thumbnail of Cardiovascular biomarkers and sex: the case for women

Nature Reviews Cardiology, 2015

Measurement of biomarkers is a critical component of cardiovascular care. Women and men differ in... more Measurement of biomarkers is a critical component of cardiovascular care. Women and men differ in their cardiac physiology and manifestations of cardiovascular disease. Although most cardiovascular biomarkers are used by clinicians without taking sex into account, sex-specific differences in biomarkers clearly exist. Baseline concentrations of many biomarkers (including cardiac troponin, natriuretic peptides, galectin-3, and soluble ST2) differ in men versus women, but these sex-specific differences do not generally translate into a need for differential sex-based cut-off points. Furthermore, most biomarkers are similarly diagnostic and prognostic, regardless of sex. Two potential exceptions are cardiac troponins measured by high-sensitivity assay, and proneurotensin. Troponin levels are lower in women than in men and, with the use of high-sensitivity assays, sex-specific cut-off points might improve the diagnosis of myocardial infarction. Proneurotensin is a novel biomarker that was found to be predictive of incident cardiovascular disease in women, but not men, and was also predictive of incident breast cancer. If confirmed, proneurotensin might be a unique biomarker of disease risk in women. With any biomarker, an understanding of sex-specific differences might improve its use and might also lead to an enhanced understanding of the physiological differences between the hearts of men and women.

Research paper thumbnail of Serial sampling of copeptin levels improves diagnosis and risk stratification in patients presenting with chest pain: results from the CHOPIN trial

Emergency medicine journal : EMJ, Jan 23, 2015

Copeptin has demonstrated a role in early rule out for acute myocardial infarction (AMI) in combi... more Copeptin has demonstrated a role in early rule out for acute myocardial infarction (AMI) in combination with a negative troponin. However, management of patients with chest pain with a positive copeptin in the setting of a negative troponin is unclear. The multicentre CHOPIN trial enrolled 2071 patients with acute chest pain. Of these, 476 subjects with an initial negative troponin but an elevated copeptin (>14 pmol/L) were included in this study. Copeptin and troponin levels were rechecked at 2 h and the final diagnosis of AMI was made by two independent, blinded cardiologists. Follow-up at 30 days was obtained for major adverse cardiac events (MACEs), including death, AMI and urgent revascularisation. Of the 476 patients analysed, 365 (76.7%) had a persistently elevated copeptin at 2 h and 111 patients (23.3%) had a copeptin that fell below the cut-off of 14 pmol/L. When the second copeptin was elevated there were 18 AMIs (4.9%) compared with 0 (0%) when the second copeptin was...

Research paper thumbnail of Prevalence of coronary artery–pulmonary artery collaterals in patients with chronic thromboembolic pulmonary hypertension

Pulmonary Circulation, 2015

This study sought to determine the prevalence of coronary artery-pulmonary artery collaterals in ... more This study sought to determine the prevalence of coronary artery-pulmonary artery collaterals in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and to correlate their presence with the degree of clot burden. CTEPH is a treatable cause of severe pulmonary hypertension and right heart failure. Bronchopulmonary collateral vessels have been used as a supplementary diagnostic and prognostic tool for this disease. Coronary artery-pulmonary artery collaterals in this population have not been described. The coronary angiograms of 300 consecutive patients with CTEPH evaluated for pulmonary thromboendarterectomy (PTE) between January 1, 2007, and May 1, 2014, were examined. Of these patients, 259 (50% male; mean age, 58.3 ± 10.6 years) had cineangiographic images deemed adequate to definitively assess for the presence of coronary artery-pulmonary artery collaterals and were included in the final analyses. Pulmonary angiogram reports were reviewed for extent of pulmonary artery obstruction. The coronary angiograms of 259 age- and sex-matched control patients were also examined. Among 259 CTEPH patients with definitive imaging, 34 coronary artery-pulmonary artery collaterals were found in 28 patients (10.8%), versus 1 coronary artery-pulmonary artery collateral among control subjects (0.4%; P < 0.001). Compared with CTEPH patients without collaterals, patients with collaterals had a significantly higher prevalence of total occlusion of their right or left main pulmonary artery (P < 0.001) or lobar arteries (P < 0.001). In conclusion, the prevalence of coronary artery-pulmonary artery collaterals in CTEPH patients undergoing coronary angiography for possible PTE is approximately 11%. These vessels are associated with more severe pulmonary artery occlusion.

Research paper thumbnail of The association between N-terminal pro B-type natriuretic peptide and lipoprotein particle concentration plateaus at higher N-terminal pro B-type natriuretic peptide values: Multi-Ethnic Study on Atherosclerosis

Metabolism, 2015

The association between N-terminal pro B-type natriuretic peptide (NT-proBNP) and blood levels of... more The association between N-terminal pro B-type natriuretic peptide (NT-proBNP) and blood levels of small and large LDL- and HDL- particle (P) concentration may not be linear throughout the whole range of NT-proBNP values. Linear spline regression analysis between NT-proBNP and lipoprotein particle concentrations was performed cross-sectionally in 5597 individuals from the Multi-Ethnic Study of Atherosclerosis adjusted for age, race, sex, body mass index, % of energy from saturated fats, intentional exercise, statin use, antihypertensive medication use, diabetes, IL-6 and estimated glomerular filtration rate. Spline knots were selected as the point at which the linear slope changed in these associations. NT-proBNP was positively associated with large LDL-P and HDL-P, but inversely associated with small LDL-P and HDL-P, but only for NT-proBNP values below the knot (range: 100-200 pg/mL). These results suggest the presence of two distinct biological mechanisms above and below the knot determining the association between NT-proBNP and lipoprotein particle concentrations.

Research paper thumbnail of Midregional Proadrenomedullin Predicts Mortality and Major Adverse Cardiac Events in Patients Presenting With Chest Pain: Results From the CHOPIN Trial

Academic Emergency Medicine, 2015

Objectives: Chest pain is a common complaint to emergency departments (EDs) and clinical risk fac... more Objectives: Chest pain is a common complaint to emergency departments (EDs) and clinical risk factors are used to predict which patients are at risk for worse outcomes and mortality. The goal was to assess the novel biomarker midregional proadrenomedullin (MR-proADM) in prediction of mortality and major adverse cardiac events (MACE).

Research paper thumbnail of State of the Art: Newer biomarkers in heart failure

European journal of heart failure, Jan 16, 2015

Since natriuretic peptides were successfully integrated into the clinical practice of heart failu... more Since natriuretic peptides were successfully integrated into the clinical practice of heart failure (HF), the possibility of using new biomarkers to advance the management of affected patients has been explored. While a huge number of candidate HF biomarkers have been described recently, very few have made the difficult translation from initial promise to clinical application. These markers mirror the complex pathophysiology of heart failure at various levels: cell loss (troponin), fibrosis (ST2 and galectin-3), infection (procalcitonin), and renal disease (several renal markers). In this review, we examine the best emerging candidates for clinical assessment and management of patients with HF.

Research paper thumbnail of Natriuretic peptides as diagnostic test: lessons from the first 5 years of clinical application

Heart failure clinics, 2006

Research paper thumbnail of Echocardiography in pulmonary vascular disease

Cardiology clinics, 2004

The assessment of pulmonary artery pressure, right ventricular function, right ventricular fillin... more The assessment of pulmonary artery pressure, right ventricular function, right ventricular filling pressure, and tricuspid regurgitation provides invaluable information in the care of patients with pulmonary vascular disease. Echocardiography provides a rapid, noninvasive, portable, and accurate method to evaluate these parameters and also provides information on left ventricular and valvular function. Echocardiography has therefore become one of the most commonly performed diagnostic studies in patients with pulmonary vascular disease, and the technique's applications in this area are likely to grow. This article presents an overview of the current uses of echocardiography in pulmonary vascular disease and pulmonary hypertension.

Research paper thumbnail of MID-REGIONAL PROADRENOMEDULLIN PREDICTS LONG-TERM MORTALITY IN PATIENTS WITH CHEST PAIN

Research paper thumbnail of Midregion prohormone adrenomedullin and prognosis in patients presenting with acute dyspnea: results from the BACH (Biomarkers in Acute Heart Failure) trial

Journal of the American College of Cardiology, Jan 30, 2011

The aim of this study was to determine the prognostic utility of midregion proadrenomedullin (MR-... more The aim of this study was to determine the prognostic utility of midregion proadrenomedullin (MR-proADM) in all patients, cardiac and noncardiac, presenting with acute shortness of breath. The recently published BACH (Biomarkers in Acute Heart Failure) study demonstrated that MR-proADM had superior accuracy for predicting 90-day mortality compared with B-type natriuretic peptide (area under the curve: 0.674 vs. 0.606, respectively, p < 0.001) in acute heart failure. The BACH trial was a prospective, 15-center, international study of 1,641 patients presenting to the emergency department with dyspnea. Using this dataset, the prognostic accuracy of MR-proADM was evaluated in all patients enrolled for predicting 90-day mortality with respect to other biomarkers, the added value in addition to clinical variables, as well as the added value of additional measurements during hospital admission. Compared with B-type natriuretic peptide or troponin, MR-proADM was superior for predicting 9...

Research paper thumbnail of Letter by Daniels et al regarding article, "Incidence, causes, and survival trends from cardiovascular-related sudden cardiac arrest in children and young adults 0 to 35 years of age

Research paper thumbnail of Does Copeptin Provide Additional Risk Stratification in Chest Pain Patients With a Mild Troponin Elevation?

Circulation

Introduction: Copeptin has demonstrated a role in early rule out for acute myocardial infarction ... more Introduction: Copeptin has demonstrated a role in early rule out for acute myocardial infarction in combination with a negative troponin. However, the value of copeptin in patients with a positive troponin is not established. Hypothesis: The addition of a baseline copeptin at chest pain presentation will improve risk stratification in patients with mild troponin elevation. Methods: The multi-center CHOPIN trial enrolled 2071 acute chest pain patients. All subjects with ST segment elevations were excluded from this analysis. Of the remaining patients, 124 had a mildly elevated troponin (defined by <2x URL) and were included in the study cohort. Baseline cTnI and copeptin levels were drawn on presentation, and another cTnI at 2 hours. Copeptin ≤14 pmol/l and troponin deltas ≤10% from baseline were considered positive. Two independent blinded cardiologists adjudicated AMI diagnosis. The value of a baseline copeptin in this cohort was assessed using AMI incidence, odds ratio, sensiti...

Research paper thumbnail of Acute Myocardial Ischemia in Adults Secondary to Missed Kawasaki Disease in Childhood

The American Journal of Cardiology, 2015

Coronary artery aneurysms that occur in 25% of untreated Kawasaki disease (KD) patients may remai... more Coronary artery aneurysms that occur in 25% of untreated Kawasaki disease (KD) patients may remain clinically silent for decades and then thrombose resulting in myocardial infarction. Although KD is now the most common cause of acquired heart disease in children in Asia, the United States, and Western Europe, the incidence of KD in Egypt is unknown. We tested the hypothesis that young adults in Egypt presenting with acute myocardial ischemia may have coronary artery lesions because of KD in childhood. We reviewed a total of 580 angiograms of patients ≤40 years presenting with symptoms of myocardial ischemia. Coronary artery aneurysms were noted in 46 patients (7.9%), of whom 9 presented with myocardial infarction. The likelihood of antecedent KD as the cause of the aneurysms was classified as definite (n = 10), probable (n = 29), or equivocal (n = 7). Compared with the definite and probable groups, the equivocal group had more traditional cardiovascular risk factors, smaller sized aneurysms, and fewer coronary arteries affected. In conclusion, in a major metropolitan center in Egypt, 6.7% of adults aged ≤40 years who underwent angiography for evaluation of possible myocardial ischemia had lesions consistent with antecedent KD. Because of the unique therapeutic challenges associated with these lesions, adult cardiologists should be aware that coronary artery aneurysms in young adults may be because of missed KD in childhood.

Research paper thumbnail of Atrial Fibrillation Impairs the Diagnostic Performance of Cardiac Natriuretic Peptides in Dyspneic Patients

JACC: Heart Failure, 2013

The purpose of this study was to assess the impact of atrial fibrillation (AF) on the performance... more The purpose of this study was to assess the impact of atrial fibrillation (AF) on the performance of mid-region amino terminal pro-atrial natriuretic peptide (MR-proANP) in comparison with the B-type peptides (BNP and NT-proBNP) for diagnosis of acute heart failure (HF) in dyspneic patients.

Research paper thumbnail of Lipoprotein Particle Concentrations in Children and Adults following Kawasaki Disease

The Journal of Pediatrics, 2014

To test the hypothesis that children and adults with a history of Kawasaki disease (KD) are more ... more To test the hypothesis that children and adults with a history of Kawasaki disease (KD) are more likely to have abnormal lipoprotein particle profiles that could place them at increased risk for developing atherosclerosis later in life. Fasting serum samples were obtained from 192 children and 63 adults with history of KD and 90 age-similar healthy controls. Lipoprotein particle concentrations and sizes were measured by nuclear magnetic resonance spectroscopy (LipoScience Inc, Raleigh, North Carolina), and serum was assayed for total cholesterol (TC), triglycerides, and high-density lipoprotein (HDL) cholesterol (HDL-C). Low-density lipoprotein (LDL) cholesterol was estimated using the Friedewald formula. Data were analyzed in a least-square means model, with adjustment for age and sex and with the use of Holm correction for multiple comparisons. Compared with respective control groups, both adult and pediatric subjects with KD had significantly lower mean very low-density lipoprotein-chylomicron particles, intermediate-density lipoproteins, triglycerides, and TC concentrations. Pediatric subjects with KD had significantly lower LDL particle and LDL cholesterol concentrations and lower mean TC/HDL-C ratio (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). In contrast, the adult subjects with KD had significantly lower HDL particle, small HDL particle, and HDL-C concentrations (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001), but HDL-C was within normal range. Nuclear magnetic resonance lipoprotein particle analysis suggests that pediatric and adult subjects with KD, regardless of their aneurysm status, are no more likely than age-similar, healthy controls to have lipid patterns associated with increased risk of atherosclerosis.

Research paper thumbnail of Review on natriuretic peptides: where we are, where we are going

Expert Opinion on Medical Diagnostics, 2008

Tremendous advances have been made in our understanding of the pathophysiology and treatment of c... more Tremendous advances have been made in our understanding of the pathophysiology and treatment of congestive heart failure. However, diagnosis of the disease still remains difficult, even with a comprehensive physical examination. Symptoms such as dyspnea are nonspecific and insensitive indicators for heart failure, which can go largely undetected. Several studies have suggested the need for new diagnostic capabilities, especially with the increasing prevalence of heart failure in the US. The discovery of natriuretic peptides as diagnostic biomarkers has been one of the most critical advances for the management of heart failure. Both B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide have the potential to diagnose heart failure, assess prognostic risk of rehospitalization and mortality, and even help guide treatment. Their relative cost-effectiveness and availability have also facilitated their acceptance into many emergency departments, clinics and in-patient units as standard care when evaluating patients with suspected heart failure. Our understanding of the natriuretic peptide system is still in its infancy, but natriuretic peptides have emerged as important diagnostic and prognostic tools that have generated interest in finding broader applications for their use. The purpose of this review is to discuss the clinical approaches and future applications of natriuretic peptides in diagnosing and managing treatment of congestive heart failure. A comprehensive review of studies to assess the utility of natriuretic peptides for diagnosis and prognosis of heart failure and other conditions. Natriuretic peptides are powerful tools to aid the physician in the diagnosis, prognosis and management of heart failure in both in-patient and out-patient settings. However, natriuretic peptides should be used as an adjunct test as many circumstances can also influence changes in natriuretic peptide levels.

Research paper thumbnail of The associations between metabolic variables and NT-proBNP are blunted at pathological ranges: The Multi-Ethnic Study of Atherosclerosis

Metabolism, 2014

Objective. Under physiological conditions brain natriuretic peptide (BNP) is inversely associated... more Objective. Under physiological conditions brain natriuretic peptide (BNP) is inversely associated with metabolic risk factors, but under pathological conditions these associations may tend to plateau.

Research paper thumbnail of Mid-Region Pro-Hormone Markers for Diagnosis and Prognosis in Acute Dyspnea

Journal of the American College of Cardiology, 2010

Our purpose was to assess the diagnostic utility of mid-regional pro-atrial natriuretic peptide (... more Our purpose was to assess the diagnostic utility of mid-regional pro-atrial natriuretic peptide (MR-proANP) for the diagnosis of acute heart failure (AHF) and the prognostic value of mid-regional pro-adrenomedullin (MR-proADM) in patients with AHF.

Research paper thumbnail of Cardiovascular biomarkers in acute Kawasaki disease

International Journal of Cardiology, 2013

Endomycocardial biopsies have demonstrated that subclinical myocarditis is a universal feature of... more Endomycocardial biopsies have demonstrated that subclinical myocarditis is a universal feature of acute Kawasaki disease (KD). We investigated biochemical evidence of myocardial strain, oxidative stress, and cardiomyocyte injury in 55 acute KD subjects (30 with paired convalescent samples), 54 febrile control (FC), and 50 healthy control (HC) children by measuring concentrations of cardiovascular biomarkers. Levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and soluble ST2 (sST2) were elevated in acute vs. convalescent KD, FC, and HC (p≤0.002), while γ-glutamyl transferase and alanine amino transferase as measures of oxidative stress were increased in acute vs. FC (p≤0.0002). Cardiac troponin I (cTnI) levels, using a highly sensitive assay, were elevated in 30% and 40% of paired acute and convalescent KD subjects, respectively, and normalized within two years of disease onset. NT-proBNP and sST2 negatively correlated with deceleration time, but only NT-proBNP correlated with MV E:A ratio and internal diameter of the coronary arteries (RCA/LAD Zworst). NT-proBNP and sST2 were elevated in acute KD subjects and correlated with impaired myocardial relaxation. These findings, combined with elevated levels of cTnI, suggest that both cardiomyocyte stress and cell death are associated with myocardial inflammation in acute KD.

Research paper thumbnail of ACUTE MYOCARDIAL ISCHEMIA IN ADULTS SECONDARY TO MISSED KAWASAKI DISEASE IN CHILDHOOD

Journal of the American College of Cardiology, 2014

Coronary artery aneurysms that occur in 25% of untreated Kawasaki disease (KD) patients may remai... more Coronary artery aneurysms that occur in 25% of untreated Kawasaki disease (KD) patients may remain clinically silent for decades and then thrombose resulting in myocardial infarction. Although KD is now the most common cause of acquired heart disease in children in Asia, the United States, and Western Europe, the incidence of KD in Egypt is unknown. We tested the hypothesis that young adults in Egypt presenting with acute myocardial ischemia may have coronary artery lesions because of KD in childhood. We reviewed a total of 580 angiograms of patients ≤40 years presenting with symptoms of myocardial ischemia. Coronary artery aneurysms were noted in 46 patients (7.9%), of whom 9 presented with myocardial infarction. The likelihood of antecedent KD as the cause of the aneurysms was classified as definite (n = 10), probable (n = 29), or equivocal (n = 7). Compared with the definite and probable groups, the equivocal group had more traditional cardiovascular risk factors, smaller sized aneurysms, and fewer coronary arteries affected. In conclusion, in a major metropolitan center in Egypt, 6.7% of adults aged ≤40 years who underwent angiography for evaluation of possible myocardial ischemia had lesions consistent with antecedent KD. Because of the unique therapeutic challenges associated with these lesions, adult cardiologists should be aware that coronary artery aneurysms in young adults may be because of missed KD in childhood.

Research paper thumbnail of Cardiovascular biomarkers and sex: the case for women

Nature Reviews Cardiology, 2015

Measurement of biomarkers is a critical component of cardiovascular care. Women and men differ in... more Measurement of biomarkers is a critical component of cardiovascular care. Women and men differ in their cardiac physiology and manifestations of cardiovascular disease. Although most cardiovascular biomarkers are used by clinicians without taking sex into account, sex-specific differences in biomarkers clearly exist. Baseline concentrations of many biomarkers (including cardiac troponin, natriuretic peptides, galectin-3, and soluble ST2) differ in men versus women, but these sex-specific differences do not generally translate into a need for differential sex-based cut-off points. Furthermore, most biomarkers are similarly diagnostic and prognostic, regardless of sex. Two potential exceptions are cardiac troponins measured by high-sensitivity assay, and proneurotensin. Troponin levels are lower in women than in men and, with the use of high-sensitivity assays, sex-specific cut-off points might improve the diagnosis of myocardial infarction. Proneurotensin is a novel biomarker that was found to be predictive of incident cardiovascular disease in women, but not men, and was also predictive of incident breast cancer. If confirmed, proneurotensin might be a unique biomarker of disease risk in women. With any biomarker, an understanding of sex-specific differences might improve its use and might also lead to an enhanced understanding of the physiological differences between the hearts of men and women.

Research paper thumbnail of Serial sampling of copeptin levels improves diagnosis and risk stratification in patients presenting with chest pain: results from the CHOPIN trial

Emergency medicine journal : EMJ, Jan 23, 2015

Copeptin has demonstrated a role in early rule out for acute myocardial infarction (AMI) in combi... more Copeptin has demonstrated a role in early rule out for acute myocardial infarction (AMI) in combination with a negative troponin. However, management of patients with chest pain with a positive copeptin in the setting of a negative troponin is unclear. The multicentre CHOPIN trial enrolled 2071 patients with acute chest pain. Of these, 476 subjects with an initial negative troponin but an elevated copeptin (>14 pmol/L) were included in this study. Copeptin and troponin levels were rechecked at 2 h and the final diagnosis of AMI was made by two independent, blinded cardiologists. Follow-up at 30 days was obtained for major adverse cardiac events (MACEs), including death, AMI and urgent revascularisation. Of the 476 patients analysed, 365 (76.7%) had a persistently elevated copeptin at 2 h and 111 patients (23.3%) had a copeptin that fell below the cut-off of 14 pmol/L. When the second copeptin was elevated there were 18 AMIs (4.9%) compared with 0 (0%) when the second copeptin was...

Research paper thumbnail of Prevalence of coronary artery–pulmonary artery collaterals in patients with chronic thromboembolic pulmonary hypertension

Pulmonary Circulation, 2015

This study sought to determine the prevalence of coronary artery-pulmonary artery collaterals in ... more This study sought to determine the prevalence of coronary artery-pulmonary artery collaterals in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and to correlate their presence with the degree of clot burden. CTEPH is a treatable cause of severe pulmonary hypertension and right heart failure. Bronchopulmonary collateral vessels have been used as a supplementary diagnostic and prognostic tool for this disease. Coronary artery-pulmonary artery collaterals in this population have not been described. The coronary angiograms of 300 consecutive patients with CTEPH evaluated for pulmonary thromboendarterectomy (PTE) between January 1, 2007, and May 1, 2014, were examined. Of these patients, 259 (50% male; mean age, 58.3 ± 10.6 years) had cineangiographic images deemed adequate to definitively assess for the presence of coronary artery-pulmonary artery collaterals and were included in the final analyses. Pulmonary angiogram reports were reviewed for extent of pulmonary artery obstruction. The coronary angiograms of 259 age- and sex-matched control patients were also examined. Among 259 CTEPH patients with definitive imaging, 34 coronary artery-pulmonary artery collaterals were found in 28 patients (10.8%), versus 1 coronary artery-pulmonary artery collateral among control subjects (0.4%; P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Compared with CTEPH patients without collaterals, patients with collaterals had a significantly higher prevalence of total occlusion of their right or left main pulmonary artery (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) or lobar arteries (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). In conclusion, the prevalence of coronary artery-pulmonary artery collaterals in CTEPH patients undergoing coronary angiography for possible PTE is approximately 11%. These vessels are associated with more severe pulmonary artery occlusion.

Research paper thumbnail of The association between N-terminal pro B-type natriuretic peptide and lipoprotein particle concentration plateaus at higher N-terminal pro B-type natriuretic peptide values: Multi-Ethnic Study on Atherosclerosis

Metabolism, 2015

The association between N-terminal pro B-type natriuretic peptide (NT-proBNP) and blood levels of... more The association between N-terminal pro B-type natriuretic peptide (NT-proBNP) and blood levels of small and large LDL- and HDL- particle (P) concentration may not be linear throughout the whole range of NT-proBNP values. Linear spline regression analysis between NT-proBNP and lipoprotein particle concentrations was performed cross-sectionally in 5597 individuals from the Multi-Ethnic Study of Atherosclerosis adjusted for age, race, sex, body mass index, % of energy from saturated fats, intentional exercise, statin use, antihypertensive medication use, diabetes, IL-6 and estimated glomerular filtration rate. Spline knots were selected as the point at which the linear slope changed in these associations. NT-proBNP was positively associated with large LDL-P and HDL-P, but inversely associated with small LDL-P and HDL-P, but only for NT-proBNP values below the knot (range: 100-200 pg/mL). These results suggest the presence of two distinct biological mechanisms above and below the knot determining the association between NT-proBNP and lipoprotein particle concentrations.

Research paper thumbnail of Midregional Proadrenomedullin Predicts Mortality and Major Adverse Cardiac Events in Patients Presenting With Chest Pain: Results From the CHOPIN Trial

Academic Emergency Medicine, 2015

Objectives: Chest pain is a common complaint to emergency departments (EDs) and clinical risk fac... more Objectives: Chest pain is a common complaint to emergency departments (EDs) and clinical risk factors are used to predict which patients are at risk for worse outcomes and mortality. The goal was to assess the novel biomarker midregional proadrenomedullin (MR-proADM) in prediction of mortality and major adverse cardiac events (MACE).

Research paper thumbnail of State of the Art: Newer biomarkers in heart failure

European journal of heart failure, Jan 16, 2015

Since natriuretic peptides were successfully integrated into the clinical practice of heart failu... more Since natriuretic peptides were successfully integrated into the clinical practice of heart failure (HF), the possibility of using new biomarkers to advance the management of affected patients has been explored. While a huge number of candidate HF biomarkers have been described recently, very few have made the difficult translation from initial promise to clinical application. These markers mirror the complex pathophysiology of heart failure at various levels: cell loss (troponin), fibrosis (ST2 and galectin-3), infection (procalcitonin), and renal disease (several renal markers). In this review, we examine the best emerging candidates for clinical assessment and management of patients with HF.

Research paper thumbnail of Natriuretic peptides as diagnostic test: lessons from the first 5 years of clinical application

Heart failure clinics, 2006

Research paper thumbnail of Echocardiography in pulmonary vascular disease

Cardiology clinics, 2004

The assessment of pulmonary artery pressure, right ventricular function, right ventricular fillin... more The assessment of pulmonary artery pressure, right ventricular function, right ventricular filling pressure, and tricuspid regurgitation provides invaluable information in the care of patients with pulmonary vascular disease. Echocardiography provides a rapid, noninvasive, portable, and accurate method to evaluate these parameters and also provides information on left ventricular and valvular function. Echocardiography has therefore become one of the most commonly performed diagnostic studies in patients with pulmonary vascular disease, and the technique's applications in this area are likely to grow. This article presents an overview of the current uses of echocardiography in pulmonary vascular disease and pulmonary hypertension.

Research paper thumbnail of MID-REGIONAL PROADRENOMEDULLIN PREDICTS LONG-TERM MORTALITY IN PATIENTS WITH CHEST PAIN

Research paper thumbnail of Midregion prohormone adrenomedullin and prognosis in patients presenting with acute dyspnea: results from the BACH (Biomarkers in Acute Heart Failure) trial

Journal of the American College of Cardiology, Jan 30, 2011

The aim of this study was to determine the prognostic utility of midregion proadrenomedullin (MR-... more The aim of this study was to determine the prognostic utility of midregion proadrenomedullin (MR-proADM) in all patients, cardiac and noncardiac, presenting with acute shortness of breath. The recently published BACH (Biomarkers in Acute Heart Failure) study demonstrated that MR-proADM had superior accuracy for predicting 90-day mortality compared with B-type natriuretic peptide (area under the curve: 0.674 vs. 0.606, respectively, p < 0.001) in acute heart failure. The BACH trial was a prospective, 15-center, international study of 1,641 patients presenting to the emergency department with dyspnea. Using this dataset, the prognostic accuracy of MR-proADM was evaluated in all patients enrolled for predicting 90-day mortality with respect to other biomarkers, the added value in addition to clinical variables, as well as the added value of additional measurements during hospital admission. Compared with B-type natriuretic peptide or troponin, MR-proADM was superior for predicting 9...

Research paper thumbnail of Letter by Daniels et al regarding article, "Incidence, causes, and survival trends from cardiovascular-related sudden cardiac arrest in children and young adults 0 to 35 years of age

Research paper thumbnail of Does Copeptin Provide Additional Risk Stratification in Chest Pain Patients With a Mild Troponin Elevation?

Circulation

Introduction: Copeptin has demonstrated a role in early rule out for acute myocardial infarction ... more Introduction: Copeptin has demonstrated a role in early rule out for acute myocardial infarction in combination with a negative troponin. However, the value of copeptin in patients with a positive troponin is not established. Hypothesis: The addition of a baseline copeptin at chest pain presentation will improve risk stratification in patients with mild troponin elevation. Methods: The multi-center CHOPIN trial enrolled 2071 acute chest pain patients. All subjects with ST segment elevations were excluded from this analysis. Of the remaining patients, 124 had a mildly elevated troponin (defined by <2x URL) and were included in the study cohort. Baseline cTnI and copeptin levels were drawn on presentation, and another cTnI at 2 hours. Copeptin ≤14 pmol/l and troponin deltas ≤10% from baseline were considered positive. Two independent blinded cardiologists adjudicated AMI diagnosis. The value of a baseline copeptin in this cohort was assessed using AMI incidence, odds ratio, sensiti...

Research paper thumbnail of Acute Myocardial Ischemia in Adults Secondary to Missed Kawasaki Disease in Childhood

The American Journal of Cardiology, 2015

Coronary artery aneurysms that occur in 25% of untreated Kawasaki disease (KD) patients may remai... more Coronary artery aneurysms that occur in 25% of untreated Kawasaki disease (KD) patients may remain clinically silent for decades and then thrombose resulting in myocardial infarction. Although KD is now the most common cause of acquired heart disease in children in Asia, the United States, and Western Europe, the incidence of KD in Egypt is unknown. We tested the hypothesis that young adults in Egypt presenting with acute myocardial ischemia may have coronary artery lesions because of KD in childhood. We reviewed a total of 580 angiograms of patients ≤40 years presenting with symptoms of myocardial ischemia. Coronary artery aneurysms were noted in 46 patients (7.9%), of whom 9 presented with myocardial infarction. The likelihood of antecedent KD as the cause of the aneurysms was classified as definite (n = 10), probable (n = 29), or equivocal (n = 7). Compared with the definite and probable groups, the equivocal group had more traditional cardiovascular risk factors, smaller sized aneurysms, and fewer coronary arteries affected. In conclusion, in a major metropolitan center in Egypt, 6.7% of adults aged ≤40 years who underwent angiography for evaluation of possible myocardial ischemia had lesions consistent with antecedent KD. Because of the unique therapeutic challenges associated with these lesions, adult cardiologists should be aware that coronary artery aneurysms in young adults may be because of missed KD in childhood.

Research paper thumbnail of Atrial Fibrillation Impairs the Diagnostic Performance of Cardiac Natriuretic Peptides in Dyspneic Patients

JACC: Heart Failure, 2013

The purpose of this study was to assess the impact of atrial fibrillation (AF) on the performance... more The purpose of this study was to assess the impact of atrial fibrillation (AF) on the performance of mid-region amino terminal pro-atrial natriuretic peptide (MR-proANP) in comparison with the B-type peptides (BNP and NT-proBNP) for diagnosis of acute heart failure (HF) in dyspneic patients.

Research paper thumbnail of Lipoprotein Particle Concentrations in Children and Adults following Kawasaki Disease

The Journal of Pediatrics, 2014

To test the hypothesis that children and adults with a history of Kawasaki disease (KD) are more ... more To test the hypothesis that children and adults with a history of Kawasaki disease (KD) are more likely to have abnormal lipoprotein particle profiles that could place them at increased risk for developing atherosclerosis later in life. Fasting serum samples were obtained from 192 children and 63 adults with history of KD and 90 age-similar healthy controls. Lipoprotein particle concentrations and sizes were measured by nuclear magnetic resonance spectroscopy (LipoScience Inc, Raleigh, North Carolina), and serum was assayed for total cholesterol (TC), triglycerides, and high-density lipoprotein (HDL) cholesterol (HDL-C). Low-density lipoprotein (LDL) cholesterol was estimated using the Friedewald formula. Data were analyzed in a least-square means model, with adjustment for age and sex and with the use of Holm correction for multiple comparisons. Compared with respective control groups, both adult and pediatric subjects with KD had significantly lower mean very low-density lipoprotein-chylomicron particles, intermediate-density lipoproteins, triglycerides, and TC concentrations. Pediatric subjects with KD had significantly lower LDL particle and LDL cholesterol concentrations and lower mean TC/HDL-C ratio (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001). In contrast, the adult subjects with KD had significantly lower HDL particle, small HDL particle, and HDL-C concentrations (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .001), but HDL-C was within normal range. Nuclear magnetic resonance lipoprotein particle analysis suggests that pediatric and adult subjects with KD, regardless of their aneurysm status, are no more likely than age-similar, healthy controls to have lipid patterns associated with increased risk of atherosclerosis.

Research paper thumbnail of Review on natriuretic peptides: where we are, where we are going

Expert Opinion on Medical Diagnostics, 2008

Tremendous advances have been made in our understanding of the pathophysiology and treatment of c... more Tremendous advances have been made in our understanding of the pathophysiology and treatment of congestive heart failure. However, diagnosis of the disease still remains difficult, even with a comprehensive physical examination. Symptoms such as dyspnea are nonspecific and insensitive indicators for heart failure, which can go largely undetected. Several studies have suggested the need for new diagnostic capabilities, especially with the increasing prevalence of heart failure in the US. The discovery of natriuretic peptides as diagnostic biomarkers has been one of the most critical advances for the management of heart failure. Both B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide have the potential to diagnose heart failure, assess prognostic risk of rehospitalization and mortality, and even help guide treatment. Their relative cost-effectiveness and availability have also facilitated their acceptance into many emergency departments, clinics and in-patient units as standard care when evaluating patients with suspected heart failure. Our understanding of the natriuretic peptide system is still in its infancy, but natriuretic peptides have emerged as important diagnostic and prognostic tools that have generated interest in finding broader applications for their use. The purpose of this review is to discuss the clinical approaches and future applications of natriuretic peptides in diagnosing and managing treatment of congestive heart failure. A comprehensive review of studies to assess the utility of natriuretic peptides for diagnosis and prognosis of heart failure and other conditions. Natriuretic peptides are powerful tools to aid the physician in the diagnosis, prognosis and management of heart failure in both in-patient and out-patient settings. However, natriuretic peptides should be used as an adjunct test as many circumstances can also influence changes in natriuretic peptide levels.

Research paper thumbnail of The associations between metabolic variables and NT-proBNP are blunted at pathological ranges: The Multi-Ethnic Study of Atherosclerosis

Metabolism, 2014

Objective. Under physiological conditions brain natriuretic peptide (BNP) is inversely associated... more Objective. Under physiological conditions brain natriuretic peptide (BNP) is inversely associated with metabolic risk factors, but under pathological conditions these associations may tend to plateau.

Research paper thumbnail of Mid-Region Pro-Hormone Markers for Diagnosis and Prognosis in Acute Dyspnea

Journal of the American College of Cardiology, 2010

Our purpose was to assess the diagnostic utility of mid-regional pro-atrial natriuretic peptide (... more Our purpose was to assess the diagnostic utility of mid-regional pro-atrial natriuretic peptide (MR-proANP) for the diagnosis of acute heart failure (AHF) and the prognostic value of mid-regional pro-adrenomedullin (MR-proADM) in patients with AHF.