W H Wilson Tang

Lerner Research Institute, Cleveland, Ohio, United States

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Publications (383)2032.33 Total impact

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    ABSTRACT: Although left ventricular (LV) dysfunction occurs not uncommonly in the course of cancer therapy, little is known about its natural history and prognostic impact on patients. To investigate the incidence, predictors, and impact on survival of LV systolic dysfunction and recovery during cancer therapy, we conducted a retrospective cohort observational study over 1 year at the University of Texas MD Anderson Cancer Center. We enrolled patients with a decrease in ejection fraction by echocardiography to <50% while undergoing cancer therapy from January 2009 to December 2009. We collected and analyzed their chart data. Of 7,648 patients with echocardiograms in 2009, 366 (4.8%) had ejection fraction <50% and 104 met study criteria. LV systolic dysfunction was associated with cardiotoxic therapy in 53 patients (51%). Recovery occurred in 57 patients (55%) and was independently predicted by younger age, smaller left atrial volume index, and lower B-type natriuretic peptide. At last follow-up, 69 patients (66%) were dead, and 35 (34%) were alive. There was a 20% advantage in 2-year survival among patients with LV systolic recovery compared with those without (95% confidence interval 4% to 41%, p = 0.02). In this retrospective study, LV systolic dysfunction recovery occurred in over half of the patients, appeared independent of cardiotoxic etiology, and associated with a 20% survival benefit at 2 years. Multivariable predictors of recovery are younger age, a small left atrial volume index, and lower B-type natriuretic peptide.
    The American journal of cardiology. 06/2014; 113(11):1893-8.
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    ABSTRACT: Neopterin is synthesized by macrophages upon stimulation with gamma-interferon, and high neopterin production is associated with cellular immune activation and increased production of reactive oxygen species (oxidant stress), but the clinical utility of urine neopterin levels in patients with heart failure (HF) has not been explored. Fifty-three ambulatory patients with chronic systolic HF (left ventricular [LV] ejection fraction ≤40%) underwent comprehensive echocardiographic evaluation and cardiopulmonary exercise testing. Urine neopterin levels were quantified by liquid chromatography with tandem mass spectrometric analyses and corrected to urine creatinine (Cr) levels. In our study cohort, median urine neopterin level was 60 μmol/mol Cr (interquartile range 40 to 86). There were modest correlations between urine neopterin levels and abnormalities in cardiac structure and function by echocardiography: LV ejection fraction (r = -0.33, p = 0.017), indexed LV end-diastolic volume (r = 0.31, p = 0.029), indexed LV end-systolic volume (r = 0.32, p = 0.024), and E/septal Ea (r = 0.28, p = 0.041). Although there was no significant correlation between urine neopterin and maximal oxygen uptake (peak VO2: r = -0.25, p = 0.07), there was a modest correlation between urine neopterin and maximal ventilation/carbon dioxide production ratio (VE/VCO2 max: r = 0.38, p = 0.005). In conclusion, increase in urine neopterin levels tracks with disease severity in patients with chronic systolic HF.
    The American journal of cardiology. 06/2014; 113(11):1839-43.
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    ABSTRACT: -We hypothesized that S100A1 is regulated during human hypertrophy and heart failure (HF), and that it may be implicated in remodeling after left ventricular assist device (LVAD). S100A1 is decreased in animal and human HF and restoration produces functional recovery in animal models and in failing human myocytes. With the potential for gene therapy, it is important to carefully explore human cardiac S100A1 regulation and its role in remodeling.
    Circulation Heart Failure 05/2014; · 6.68 Impact Factor
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    ABSTRACT: Treatment of acute decompensated heart failure with loop diuretics such as furosemide is frequently complicated by insufficient urine sodium excretion. We hypothesize that insufficient natriuretic response to diuretic therapy, characterized by lower urine sodium (UNa) and urine furosemide is associated with subsequent inadequate decongestion, worsening renal function, and adverse long term events. We enrolled 52 consecutive patients with ADHF and measured serum and urine sodium (UNa), urine creatinine (UCr), and urine furosemide (UFurosemide) levels on a spot sample taken after treatment with continuous intravenous furosemide, and followed clinical and renal variables as well as adverse long-term clinical outcomes (death, rehospitalizations and cardiac transplant). We observed comparable correlations between UNa:UFurosemide ratio as well as UNa and fractional excretion of sodium (FENa) with 24-hour net urine output (r=0.52-0.64, all p<0.01) and 24-hour weight loss (r=0.44-0.56, all p<0.01). Interestingly, FENa (but not UNa or UNa:UFurosemide) were influenced by estimated glomerular filtration rate (eGFR). We observed an association between lower UNa:UFurosemide with greater likelihood of worsening renal function (HR 3.01, p=0.02) and poorer adverse clinical outcomes (HR 1.63, p=0.008) after adjusting for age and eGFR. Meanwhile, both diminished weight loss and net fluid output over 24 hours of continuous intravenous furosemide were observed when UNa:UFurosemide ratios were <2 mmol/mg or when UNa <50 mmol. In patients with ADHF receiving continuous furosemide infusion, impaired natriuretic response to furosemide is associated with greater likelihood of worsening renal function and future adverse long-term outcomes that is independent and incremental to intrinsic glomerular filtration.
    Journal of cardiac failure 04/2014; · 3.25 Impact Factor
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    ABSTRACT: Elevated levels of plasma trimethylamine N-oxide (TMAO), the product of gut microbiome and hepatic-mediated metabolism of dietary choline and l-carnitine, have recently been identified as a novel risk factor for the development of atherosclerosis in mice and humans. The goal of this study was to identify the genetic factors associated with plasma TMAO levels. We used comparative genome-wide association study approaches to discover loci for plasma TMAO levels in mice and humans. A genome-wide association study in the hybrid mouse diversity panel identified a locus for TMAO levels on chromosome 3 (P=2.37×10(-6)) that colocalized with a highly significant (P=1.07×10(-20)) cis-expression quantitative trait locus for solute carrier family 30 member 7. This zinc transporter could thus represent ≥1 positional candidate gene responsible for the association signal at this locus in mice. A genome-wide association study for plasma TMAO levels in 1973 humans identified 2 loci with suggestive evidence of association (P=3.0×10(-7)) on chromosomes 1q23.3 and 2p12. However, genotyping of the lead variants at these loci in 1892 additional subjects failed to replicate their association with plasma TMAO levels. The results of these limited observational studies indicate that, at least in humans, genes play a marginal role in determining TMAO levels and that any genetic effects are relatively weak and complex. Variation in diet or the repertoire of gut microbiota may be more important determinants of plasma TMAO levels in mice and humans, which should be investigated in future studies.
    Arteriosclerosis Thrombosis and Vascular Biology 03/2014; · 6.34 Impact Factor
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    ABSTRACT: Right ventricular (RV) global longitudinal strain (RV strain) is a sensitive measure of RV mechanics. Its relationship with standard clinical markers and long-term events in chronic systolic heart failure is not well established. The aim of this study was to examine the ability of RV strain to provide incremental prognostic value to left ventricular (LV) ejection fraction (LVEF) in patients with chronic systolic heart failure. In 171 patients with chronic systolic heart failure (LVEF ≤ 35%), a retrospective substudy of RV strain was performed using Velocity Vector Imaging to analyze previously recorded, comprehensive echocardiographic images. Death, cardiac transplantation, and heart failure hospitalization were tracked for 5 years. In this study cohort (mean age, 57 ± 14 years; mean LVEF, 25 ± 6%), mean RV strain was -11.6 ± 5.4%. More impaired RV strain was associated with increasing New York Heart Association class (rank-sums P < .0001) and greater LV volume (LV end-systolic volume index: r = 0.35, P < .0001). Worse RV strain was associated with reduced LVEF (r = -0.45, P < .0001), worse LV diastolic dysfunction (E/e' septal: r = 0.19, P = .017; left atrial volume index: r = 0.18, P = .031), and standard indices of RV systolic and diastolic dysfunction (RV s': r = -0.43, P < .0001; RV e'/a': r = 0.16, P = .0040; right atrial volume index: r = 0.20, P = .015). RV strain predicted long-term adverse events (hazard ratio, 1.30; 95% confidence interval, 1.02-1.70; P = .037). Furthermore, RV strain ≥ -14.8% predicted adverse events after adjustment for age, LVEF, RV s', E/e' septal, and right atrial volume index. In patients with chronic systolic heart failure, worse RV strain provides prognostic value incremental to LV function.
    Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 03/2014; · 2.98 Impact Factor
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    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 03/2014; 33(3):318-20. · 3.54 Impact Factor
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    ABSTRACT: We previously reported that apolipoprotein A-I (apoA-I) is oxidatively modified in the artery wall at tyrosine 166 (Y166), serving as a preferred site for post-translational modification through nitration. Recent studies, however, question the extent and functional importance of apoA-I Y166 nitration based upon studies of HDL-like particles recovered from atherosclerotic lesions. We developed a monoclonal antibody (mAb 4G11.2) that recognizes, in both free and HDL-bound forms, apoA-I site-specifically nitrated at residue 166 (166YNO2-apoA-I) to investigate the presence, distribution and function of this modified apoA-I form in atherosclerotic and normal artery wall. We also developed recombinant apoA-I with site-specific 3-nitrotyrosine incorporation only at position 166 using an evolved orthogonal nitroY-aminoacyl-tRNA synthetase/tRNACUA pair for functional studies. Studies with mAb 4G11.2 show 166YNO2-apoA-I is easily detected in atherosclerotic human coronary arteries, accounts for ~8% of total apoA-I within the artery wall, but is nearly undetectable (>100-fold less) in normal coronary arteries. Buoyant density ultracentrifugation analyses shows 166YNO2-apoA-I exists as a lipid-poor lipoprotein, with <3% recovered within the HDL-like fraction (d=1.063-1.21). 166YNO2-apoA-I in plasma shows similar distribution. Recovery of 166YNO2-apoA-I using immobilized mAb 4G11.2 shows an apoA-I form with 88.1+/-8.5% reduction in LCAT activity, a finding corroborated using a recombinant apoA-I specifically designed to include the unnatural amino acid exclusively at position 166. Site-specific nitration of apoA-I at Y166 is thus an abundant modification within the artery wall that results in selective functional impairments. Plasma levels of this modified apoA-I form may provide insights into a pathophysiological process within the diseased artery wall.
    Journal of Biological Chemistry 02/2014; · 4.65 Impact Factor
  • Adam Mohmand-Borkowski, W H Wilson Tang
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    ABSTRACT: While atrial fibrillation is common comorbidity in patients with cardiomyopathy and heart failure, diagnosis and management often focuses on tackling rate and rhythm control rather than elucidating pathogenic mechanisms related to underlying myocardial substrates. This review summarizes our current understanding of the natural history of cardiomyopathies presenting with atrial fibrillation, and the importance of managing underlying cardiomyopathic condition as diagnostic and treatment strategy for atrial fibrillation.
    Heart Failure Reviews 02/2014; · 4.45 Impact Factor
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    ABSTRACT: Recent metabolomics and animal model studies show trimethylamine-N-oxide (TMAO), an intestinal microbiota-dependent metabolite formed from dietary trimethylamine-containing nutrients such as phosphatidylcholine (PC), choline, and carnitine, is linked to coronary artery disease pathogenesis. Our aim was to examine the prognostic value of systemic choline and betaine levels in stable cardiac patients. We examined the relationship between fasting plasma choline and betaine levels and risk of major adverse cardiac events (MACE = death, myocardial infraction, stroke) in relation to TMAO over 3 years of follow-up in 3903 sequential stable subjects undergoing elective diagnostic coronary angiography. In our study cohort, median (IQR) TMAO, choline, and betaine levels were 3.7 (2.4-6.2)μM, 9.8 (7.9-12.2)μM, and 41.1 (32.5-52.1)μM, respectively. Modest but statistically significant correlations were noted between TMAO and choline (r = 0.33, P < 0.001) and less between TMAO and betaine (r = 0.09, P < 0.001). Higher plasma choline and betaine levels were associated with a 1.9-fold and 1.4-fold increased risk of MACE, respectively (Quartiles 4 vs. 1; P < 0.01, each). Following adjustments for traditional cardiovascular risk factors and high-sensitivity C-reactive protein, elevated choline [1.34 (1.03-1.74), P < 0.05], and betaine levels [1.33 (1.03-1.73), P < 0.05] each predicted increased MACE risk. Neither choline nor betaine predicted MACE risk when TMAO was added to the adjustment model, and choline and betaine predicted future risk for MACE only when TMAO was elevated. Elevated plasma levels of choline and betaine are each associated with incident MACE risk independent of traditional risk factors. However, high choline and betaine levels are only associated with higher risk of future MACE with concomitant increase in TMAO.
    European Heart Journal 02/2014; · 14.10 Impact Factor
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    ABSTRACT: Recent studies have broadened the potential use of MRA in patients with systolic heart failure following cardiovascular hospitalization. Real-world data on safety and tolerability of MRA initiation during hospitalization for ADHF are lacking. We examined the patterns of utilization of mineralocorticoid receptor antagonists (MRA) in patients admitted for acute decompensated heart failure (ADHF) in contemporary clinical practice. We reviewed consecutive hospitalized patients admitted with a primary diagnosis of ADHF between March and June 2011. The treatment patterns of MRA use or discontinuation before, during, and after hospitalization were reviewed and analyzed retrospectively. In our study cohort of 500 patients, 106 patients (21%) were on MRA prior to admission. During hospitalization, pre-admission and newly started MRA were discontinued in 64 out of 177 (36%), with worsening renal function being the most common identifiable reason. In a multivariate analysis, high admission creatinine was the only significant predictor of MRA discontinuation during hospitalization (P=0.01). Of the 394 patients who did not receive MRA before admission, 81 were eligible for MRA, but only 17 (21%) were initiated. After a median follow up of 57 days, 21 additional patients discontinued MRA; of 72 eligible patients for MRA, 55 patients (76%) were still appropriately taking it. Despite recent data, MRA are still underutilized in patients admitted with ADHF who are otherwise eligible for it. Elevated serum creatinine and worsening of renal function are the most common cause of in-hospital discontinuation, which highlights the importance of meticulous follow-up after MRA initiation.
    Journal of cardiac failure 01/2014; · 3.25 Impact Factor
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    ABSTRACT: Recent studies have indicated that high-density lipoproteins (HDLs) and their major structural protein, apolipoprotein A1 (apoA1), recovered from human atheroma are dysfunctional and are extensively oxidized by myeloperoxidase (MPO). In vitro oxidation of either apoA1 or HDL particles by MPO impairs their cholesterol acceptor function. Here, using phage display affinity maturation, we developed a high-affinity monoclonal antibody that specifically recognizes both apoA1 and HDL that have been modified by the MPO-H2O2-Cl(-) system. An oxindolyl alanine (2-OH-Trp) moiety at Trp72 of apoA1 is the immunogenic epitope. Mutagenesis studies confirmed a critical role for apoA1 Trp72 in MPO-mediated inhibition of the ATP-binding cassette transporter A1 (ABCA1)-dependent cholesterol acceptor activity of apoA1 in vitro and in vivo. ApoA1 containing a 2-OH-Trp72 group (oxTrp72-apoA1) is in low abundance within the circulation but accounts for 20% of the apoA1 in atherosclerosis-laden arteries. OxTrp72-apoA1 recovered from human atheroma or plasma is lipid poor, virtually devoid of cholesterol acceptor activity and demonstrated both a potent proinflammatory activity on endothelial cells and an impaired HDL biogenesis activity in vivo. Elevated oxTrp72-apoA1 levels in subjects presenting to a cardiology clinic (n = 627) were associated with increased cardiovascular disease risk. Circulating oxTrp72-apoA1 levels may serve as a way to monitor a proatherogenic process in the artery wall.
    Nature medicine 01/2014; · 27.14 Impact Factor
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    ABSTRACT: Neopterin is synthesized by macrophages upon stimulation with gamma-interferon, and high neopterin production is associated with cellular immune activation and increased production of reactive oxygen species (oxidant stress), but the clinical utility of urine neopterin levels in patients with heart failure (HF) has not been explored. Fifty-three ambulatory patients with chronic systolic HF (left ventricular [LV] ejection fraction ≤40%) underwent comprehensive echocardiographic evaluation and cardiopulmonary exercise testing. Urine neopterin levels were quantified by liquid chromatography with tandem mass spectrometric analyses and corrected to urine creatinine (Cr) levels. In our study cohort, median urine neopterin level was 60 μmol/mol Cr (interquartile range 40 to 86). There were modest correlations between urine neopterin levels and abnormalities in cardiac structure and function by echocardiography: LV ejection fraction (r = −0.33, p = 0.017), indexed LV end-diastolic volume (r = 0.31, p = 0.029), indexed LV end-systolic volume (r = 0.32, p = 0.024), and E/septal Ea (r = 0.28, p = 0.041). Although there was no significant correlation between urine neopterin and maximal oxygen uptake (peak VO2: r = −0.25, p = 0.07), there was a modest correlation between urine neopterin and maximal ventilation/carbon dioxide production ratio (VE/VCO2 max: r = 0.38, p = 0.005). In conclusion, increase in urine neopterin levels tracks with disease severity in patients with chronic systolic HF.
    The American Journal of Cardiology. 01/2014; 113(11):1839–1843.
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    ABSTRACT: Background Inflammation is associated with progression of chronic HF. Few data exist on hsCRP levels and their importance in acute HF. Methods and Results In the ASCEND-HF trial biomarker substudy, we measured hsCRP levels at admission (N=794), 48-72h (N=677), and 30 days (N=581) and evaluated their association with outcomes. Levels of hsCRP were considerably elevated at admission (median: 12.6 mg/L; interquartile range [IQR]: 5.23, 30.5) and 48-72h (median: 11.0 mg/L; IQR: 4.87, 29.9), and only declined at 30 days (median: 4.7 mg/L; IQR 1.83, 13.1). Admission hsCRP was not associated with dyspnea improvement at 6h (74.1%) and 24h (86.2%), in-hospital death or worsening HF (N=37, 4.7%), 30-day mortality or HF readmission (death N=25, 3.2%; combined death and HF readmission N=95, 12.0%), or 180-day mortality (N=96, 12.1%). Hospital stay (median, 5; IQR 3, 7) was longer among patients with higher admission hsCRP levels (0.57 days per log2-hsCRP in adjusted models; 95% confidence interval [CI]: 0.33, 0.81; P<0.001). Levels of hsCRP at 48-72h did not predict 30-day mortality or HF readmission and were only marginally associated with 180-day mortality. However, higher hsCRP at 30 days among survivors was associated with higher 180-day mortality in models including admission hsCRP (adjusted hazard ratio [HR] per log2-hsCRP: 1.23; 95% CI: 1.04, 1.45; P=0.016). Patients with an hsCRP increase at day 30, defined as more than 10% increase over baseline value, had higher 180-day mortality risk compared to those with an unchanged or decreased 30-day hsCRP (HR: 2.29; 95% CI: 1.16, 4.52; P=0.017). Conclusions Levels of hsCRP are elevated among patients with acute HF. Increasing levels at 30 days post-discharge are associated with higher 180-day mortality.
    Journal of cardiac failure 01/2014; · 3.25 Impact Factor
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    ABSTRACT: Background Treatment of acute decompensated heart failure with loop diuretics such as furosemide is frequently complicated by insufficient urine sodium excretion. We hypothesize that insufficient natriuretic response to diuretic therapy, characterized by lower urine sodium (UNa) and urine furosemide is associated with subsequent inadequate decongestion, worsening renal function, and adverse long term events. Methods and Results We enrolled 52 consecutive patients with ADHF and measured serum and urine sodium (UNa), urine creatinine (UCr), and urine furosemide (UFurosemide) levels on a spot sample taken after treatment with continuous intravenous furosemide, and followed clinical and renal variables as well as adverse long-term clinical outcomes (death, rehospitalizations and cardiac transplant). We observed comparable correlations between UNa:UFurosemide ratio as well as UNa and fractional excretion of sodium (FENa) with 24-hour net urine output (r=0.52-0.64, all p<0.01) and 24-hour weight loss (r=0.44-0.56, all p<0.01). Interestingly, FENa (but not UNa or UNa:UFurosemide) were influenced by estimated glomerular filtration rate (eGFR). We observed an association between lower UNa:UFurosemide with greater likelihood of worsening renal function (HR 3.01, p=0.02) and poorer adverse clinical outcomes (HR 1.63, p=0.008) after adjusting for age and eGFR. Meanwhile, both diminished weight loss and net fluid output over 24 hours of continuous intravenous furosemide were observed when UNa:UFurosemide ratios were <2 mmol/mg or when UNa <50 mmol. Conclusion In patients with ADHF receiving continuous furosemide infusion, impaired natriuretic response to furosemide is associated with greater likelihood of worsening renal function and future adverse long-term outcomes that is independent and incremental to intrinsic glomerular filtration.
    Journal of Cardiac Failure. 01/2014;
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    ABSTRACT: Although left ventricular (LV) dysfunction occurs not uncommonly in the course of cancer therapy, little is known about its natural history and prognostic impact on patients. To investigate the incidence, predictors, and impact on survival of LV systolic dysfunction and recovery during cancer therapy, we conducted a retrospective cohort observational study over 1 year at the University of Texas MD Anderson Cancer Center. We enrolled patients with a decrease in ejection fraction by echocardiography to <50% while undergoing cancer therapy from January 2009 to December 2009. We collected and analyzed their chart data. Of 7,648 patients with echocardiograms in 2009, 366 (4.8%) had ejection fraction <50% and 104 met study criteria. LV systolic dysfunction was associated with cardiotoxic therapy in 53 patients (51%). Recovery occurred in 57 patients (55%) and was independently predicted by younger age, smaller left atrial volume index, and lower B-type natriuretic peptide. At last follow-up, 69 patients (66%) were dead, and 35 (34%) were alive. There was a 20% advantage in 2-year survival among patients with LV systolic recovery compared with those without (95% confidence interval 4% to 41%, p = 0.02). In this retrospective study, LV systolic dysfunction recovery occurred in over half of the patients, appeared independent of cardiotoxic etiology, and associated with a 20% survival benefit at 2 years. Multivariable predictors of recovery are younger age, a small left atrial volume index, and lower B-type natriuretic peptide.
    The American Journal of Cardiology. 01/2014; 113(11):1893–1898.
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    ABSTRACT: -Rather than the absolute dose of diuretic or urine output, the primary signal of interest when evaluating diuretic responsiveness is the efficiency with which the kidneys can produce urine after a given dose of diuretic. As a result, we hypothesized that a metric of diuretic efficiency (DE) would capture distinct prognostic information beyond that of raw fluid output or diuretic dose. -We independently analyzed two cohorts: 1) consecutive admissions at the University of Pennsylvania (Penn) with a primary discharge diagnosis of HF (n=657) and 2) patients in the ESCAPE dataset (n=390). DE was estimated as the net fluid output produced per 40 mg of furosemide equivalents, then dichotomized into high vs. low DE based on the median value. There was only a moderate correlation between DE and both the IV diuretic dose and net fluid output (r(2) ≤ 0.26 for all comparisons), indicating that the diuretic efficiency was describing unique information. With the exception of metrics of renal function and pre-admission diuretic therapy, traditional baseline characteristics including right heart catheterization variables were not consistently associated with DE. Low DE was associated with worsened survival even after adjusting for in-hospital diuretic dose, fluid output, in addition to baseline characteristics (Penn HR=1.36, 95% CI 1.04-1.78, p=0.02; ESCAPE HR= 2.86, 95% CI 1.53-5.36, p=0.001. -Although in need of validation in less selected populations, low diuretic efficiency during decongestive therapy portends poorer long-term outcomes above and beyond traditional prognostic factors in patients hospitalized with decompensated heart failure.
    Circulation Heart Failure 12/2013; · 6.68 Impact Factor
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    ABSTRACT: Amyloidosis is an infiltrative disease characterized by deposition of amyloid fibrils within the extracellular tissue of one or multiple organs. Involvement of the heart, cardiac amyloidosis, is recognized as a common cause of restrictive cardiomyopathy and heart failure. The two major types of cardiac amyloidosis are cardiac amyloid light-chain (AL) and transthyretin-related cardiac amyloidosis (ATTR, mutant and wild types) (Nat Rev Cardiol 2010;7:398-408). While early recognition of cardiac amyloidosis is of major clinical importance, so is the ability to differentiate between subtypes. Indeed, both prognosis and therapeutic options vary drastically depending on the subtype. While endomyocardial biopsy with immunostaining is considered the gold standard, advances in imaging provide an attractive non-invasive alternative. Currently, electrocardiography, echocardiography, and cardiac magnetic resonance imaging are all used in the evaluation of cardiac amyloidosis with varying diagnostic and prognostic accuracy. Yet, none of these modalities can effectively differentiate the cardiac amyloid subtypes. Recent data with (99m)Tc-phosphate derivatives, previously used as bone seeking radioactive tracers, have shown promising results; these radiotracers selectively bind ATTR, but not AL subtype, and can differentiate subtypes with high diagnostic accuracy. This review will initially present the non-radionuclide imaging techniques and then focus on the radionuclide imaging techniques, particularly (99m)Tc-DPD and (99m)Tc-PYP, mechanism of action, performance and interpretation of the study, diagnostic accuracy, prognostic value, future clinical perspective, and outlook.
    Journal of Nuclear Cardiology 12/2013; · 2.85 Impact Factor
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    ABSTRACT: In ambulatory patients with heart failure (HF) and reduced ejection fraction (rEF), renin-angiotensin system (RAS) and β-blockers at guideline-recommended target dose reduce all-cause mortality and readmissions. Benefits in HF with preserved ejection fraction (pEF), as well as uptitration after a hospitalization, remain uncertain. This study assesses the impact of RAS- and β-blocker uptitrations in patients with HFrEF versus HFpEF during and immediately after a hospital admission. In consecutive patients (209 HFrEF with left ventricular ejection fraction <40% and 108 HFpEF with left ventricular ejection fraction ≥40%), RAS- and β-blocker dose changes were followed during 6 months after an index HF hospitalization. Patients with a RAS- and β-blocker dose increase of ≥10% of the recommended target dose were compared with patients without uptitration. Patients who received uptitration were significantly younger, with a higher heart rate and better renal function, and received spironolactone more often. Both RAS- and β-blocker uptitrations were associated with significant reductions in the composite end-point of all-cause mortality or HF readmissions in HFrEF (hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.22 to 0.60 and HR 0.51, 95% CI 0.32 to 0.81, respectively). After correction for age, heart rate, blood pressure, renal function, and spironolactone use, this association remained significant for RAS blockers (HR 0.54, 95% CI 0.31 to 0.93, p = 0.027) but not for β-blockers (HR 0.65, 95% CI 0.39 to 1.09, p = 0.101). No benefit of RAS- or β-blocker uptitration was observed in HFpEF. In conclusion, uptitration of neurohumoral blockers after an HF hospitalization is more frequently performed in younger patients with low co-morbidity burden. RAS-blocker uptitration independently predicts clinical outcome in patients with HFrEF but not in those with HFpEF.
    The American journal of cardiology 12/2013; 112(12):1913-20. · 3.58 Impact Factor
  • Mark E Dunlap, W H Wilson Tang
    Journal of cardiac failure 12/2013; · 3.25 Impact Factor

Publication Stats

4k Citations
2,032.33 Total Impact Points

Institutions

  • 2008–2014
    • Lerner Research Institute
      • Department of Cellular and Molecular Medicine
      Cleveland, Ohio, United States
  • 2003–2014
    • Cleveland Clinic
      • • Department of Cardiovascular Medicine
      • • Department of Cardiology
      Cleveland, Ohio, United States
    • Concordia University–Ann Arbor
      Ann Arbor, Michigan, United States
  • 2013
    • Dallas Nursing Institute
      Dallas, Texas, United States
    • University of Nebraska Medical Center
      Omaha, Nebraska, United States
    • Hospital of the University of Pennsylvania
      • Department of Biostatistics and Epidemiology
      Philadelphia, Pennsylvania, United States
    • Case Western Reserve University School of Medicine
      Cleveland, Ohio, United States
    • Harvard Medical School
      Boston, Massachusetts, United States
    • Johns Hopkins Medicine
      • Division of Cardiology
      Baltimore, Maryland, United States
  • 2012–2013
    • University of Washington Seattle
      • • Department of Epidemiology
      • • Division of Cardiology
      Seattle, Washington, United States
    • Universiteit Hasselt
      • Faculty of Medicine and Life Sciences
      Flanders, Belgium
    • Lovelace Respiratory Research Institute
      Albuquerque, New Mexico, United States
    • University of Minnesota Duluth
      Duluth, Minnesota, United States
    • Memorial Sloan-Kettering Cancer Center
      New York City, New York, United States
    • Emory University
      • Division of Cardiology
      Atlanta, GA, United States
    • Brigham and Women's Hospital
      • Department of Medicine
      Boston, MA, United States
  • 2009–2013
    • Ziekenhuis Oost Limburg
      • Department of Cardiology
      Genk, VLG, Belgium
    • University of Michigan
      Ann Arbor, Michigan, United States
    • Baylor College of Medicine
      • Section of Cardiology
      Houston, TX, United States
    • Arizona Heart Foundation
      Phoenix, Arizona, United States
  • 2011
    • Medtronic
      Minneapolis, Minnesota, United States
    • Dalhousie University
      Halifax, Nova Scotia, Canada
    • University of Southern California
      • Department of Preventive Medicine
      Los Angeles, CA, United States
  • 2010
    • The University of Chicago Medical Center
      • Department of Medicine
      Chicago, IL, United States
    • Metropolitan Heart and Vascular Institute
      Minneapolis, Minnesota, United States
  • 2007
    • IST Austria
      Klosterneuberg, Lower Austria, Austria
  • 2006
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States
  • 2005–2006
    • Case Western Reserve University
      • Division of Cardiovascular Medicine
      Cleveland, OH, United States
  • 2004
    • Stanford University
      • Division of Cardiovascular Medicine
      Stanford, CA, United States
  • 1999–2002
    • Stanford Medicine
      • Division of Cardiovascular Medicine
      Stanford, California, United States