W H Wilson Tang

Lerner Research Institute, Cleveland, Ohio, United States

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Publications (530)3456.97 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Natriuretic peptides (NPs) represent a critical pathway in heart failure (HF). We explored genetic determinants of pharmacodynamic effects of B-type NP (BNP) and changes in plasma cyclic guanosine monophosphate (cGMP) and blood pressure (BP). HF patients (n = 135) received recombinant human BNP (nesiritide) at standard doses, and plasma cGMP levels were measured at baseline and during infusion. We tested the association of 119 single nucleotide polymorphisms (SNPs) in 4 candidate genes (NPR1, NPR2, NPR3, and membrane metallo-endopeptidase (MME)) with the change in cGMP and BP. Gene-based testing for association of genetic variation with endpoints was significant only for MME. Upon individual SNP testing, two loci in MME were associated with ΔcGMP; another (rs16824656) showed association with BP change. In summary, the pharmacodynamic effects of BNP vary substantially in HF patients and are associated with genetic variation in MME. MME genetic variation may be an important determinant of NP-mediated effects in humans.
    Journal of Cardiovascular Translational Research 11/2015; DOI:10.1007/s12265-015-9660-2 · 3.02 Impact Factor
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    ABSTRACT: Background Nitrates are commonly prescribed to enhance activity tolerance in patients with heart failure and a preserved ejection fraction. We compared the effect of isosorbide mononitrate or placebo on daily activity in such patients. Methods In this multicenter, double-blind, crossover study, 110 patients with heart failure and a preserved ejection fraction were randomly assigned to a 6-week dose-escalation regimen of isosorbide mononitrate (from 30 mg to 60 mg to 120 mg once daily) or placebo, with subsequent crossover to the other group for 6 weeks. The primary end point was the daily activity level, quantified as the average daily accelerometer units during the 120-mg phase, as assessed by patient-worn accelerometers. Secondary end points included hours of activity per day during the 120-mg phase, daily accelerometer units during all three dose regimens, quality-of-life scores, 6-minute walk distance, and levels of N-terminal pro-brain natriuretic peptide (NT-proBNP). Results In the group receiving the 120-mg dose of isosorbide mononitrate, as compared with the placebo group, there was a nonsignificant trend toward lower daily activity (-381 accelerometer units; 95% confidence interval [CI], -780 to 17; P=0.06) and a significant decrease in hours of activity per day (-0.30 hours; 95% CI, -0.55 to -0.05; P=0.02). During all dose regimens, activity in the isosorbide mononitrate group was lower than that in the placebo group (-439 accelerometer units; 95% CI, -792 to -86; P=0.02). Activity levels decreased progressively and significantly with increased doses of isosorbide mononitrate (but not placebo). There were no significant between-group differences in the 6-minute walk distance, quality-of-life scores, or NT-proBNP levels. Conclusions Patients with heart failure and a preserved ejection fraction who received isosorbide mononitrate were less active and did not have better quality of life or submaximal exercise capacity than did patients who received placebo. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT02053493 .).
    New England Journal of Medicine 11/2015; DOI:10.1056/NEJMoa1510774 · 55.87 Impact Factor

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    ABSTRACT: Background Cardiac dysfunction influences candidate selection for kidney transplantation. There is a paucity of data regarding predictors of myocardial recovery following kidney transplantation and long-term outcomes. Objectives The purpose of this study was to identify the extent of reverse remodeling in our kidney transplant population and the predictors of such changes, and to assess outcomes in these patients. Methods We reviewed 232 patients who underwent kidney transplantation at the Cleveland Clinic from 2003 to 2013 and who had baseline and post-transplant echocardiograms; patients with simultaneous heart transplantation were excluded. Results Post-transplantation mean left ventricular ejection fraction (LVEF) improved in those with LV dysfunction (increased from 41% to 50%; p < 0.0001; n = 66). There was significant improvement in other parameters, including diastolic function, LV end-diastolic dimension, LV mass, and right ventricular systolic pressure. After adjusting for multiple clinical variables, increased hemoglobin following transplantation was associated with an improved LVEF (odds ratio: 1.50; 95% confidence interval [CI]: 1.07 to 2.14; p = 0.016) and reduced mortality (hazard ratio [HR]: 0.65; 95% CI: 0.49 to 0.87; p = 0.004). An improved LVEF <10% predicted survival independently of a pre-transplantation LVEF (HR: 0.46; 95% CI: 0.21 to 0.93; p = 0.031). Conclusions Kidney transplantation is associated with improved cardiac structure and function. A rise in post-transplantation hemoglobin was a significant factor associated with such changes, in addition to conferring a survival advantage.
    Journal of the American College of Cardiology 10/2015; 66(16):1779-1787. DOI:10.1016/j.jacc.2015.08.023 · 16.50 Impact Factor
  • Loon Yee Louis Teo · Rocio T Moran · W H Wilson Tang ·
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    ABSTRACT: The understanding of the genetic basis of cardiomyopathy has expanded significantly over the past 2 decades. The increasing availability, shortening diagnostic time, and lowering costs of genetic testing have provided researchers and physicians with the opportunity to identify the underlying genetic determinants for thousands of genetic disorders, including inherited cardiomyopathies, in effort to improve patient morbidities and mortality. As such, genetic testing has advanced from basic scientific research to clinical application and has been incorporated as part of patient evaluations for suspected inherited cardiomyopathies. Genetic evaluation framework of inherited cardiomyopathies typically encompasses careful evaluation of family history, genetic counseling, clinical screening of family members, and if appropriate, molecular genetic testing. This review summarizes the genetics, current guideline recommendations, and evidence supporting the genetic evaluation framework of five hereditary forms of cardiomyopathy: dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), restrictive cardiomyopathy (RCM), and left ventricular noncompaction (LVNC).
    Current Heart Failure Reports 10/2015; 12(6). DOI:10.1007/s11897-015-0271-7
  • W.H. Wilson Tang · Stanley L Hazen ·

    Obesity 10/2015; DOI:10.1002/oby.21250 · 3.73 Impact Factor
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    ABSTRACT: Aims: A longitudinal and comprehensive analysis of health-related quality of life (HRQOL) was performed during hospitalization for heart failure (HF) or soon after discharge. Methods and results: A post-hoc analysis was performed of the ASCEND-HF trial. The EuroQOL five dimensions questionnaire (EQ-5D) was administered to study participants at baseline, 24 h, discharge/day 10, and day 30. EQ-5D includes functional dimensions mapped to corresponding utility scores (i.e. 0 = death and 1 = perfect health), and a visual analogue scale (VAS) ranging from 0 (i.e. 'worst imaginable health state') to 100 (i.e. 'best imaginable health state'). The association between baseline and discharge EQ-5D measurements and subsequent clinical outcomes including death and rehospitalization were assessed using multivariable logistic regression and Cox proportional hazards regression. A total of 6943 patients (97%) had complete EQ-5D data at baseline. Mapped utility and VAS scores (mean ± SD) increased over time, respectively, from 0.56 ± 0.23 and 45 ± 22 at baseline to 0.67 ± 0.26 and 58 ± 22 at 24 h and to 0.79 ± 0.20 and 68 ± 22 at discharge, and remained stable at day 30. Lower mapped utility scores at baseline [odds ratio (OR) per 0.1 decrease in utility score 1.03, 95% confidence interval (CI) 1.00-1.06] and discharge (OR 1.10, 95% CI 1.05-1.15) and VAS scores at baseline (OR per 10 point decrease 1.05, 95% CI 1.01-1.09) were significantly associated with increased risk of 30-day all-cause death or HF rehospitalization. Conclusions: Patients hospitalized for HF had severely impaired health status at baseline and, although this improved substantially during admission, health status remained abnormal at discharge.
    European Journal of Heart Failure 10/2015; DOI:10.1002/ejhf.420 · 6.53 Impact Factor
  • Yuji Nagatomo · W.H. Wilson Tang ·
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    ABSTRACT: Microbes play an important role in human health and disease. In the setting of heart failure (HF), substantial hemodynamic changes such as hypoperfusion and congestion in the intestines can alter gut morphology, permeability, function, and possibly the growth and composition of gut microbiota. These changes can disrupt the barrier function of the intestines, and exacerbate systemic inflammation through microbial or endotoxin translocation into systemic circulation. Furthermore, cardio-renal alterations via metabolites derived from gut microbiota can potentially mediate or modulate HF pathophysiology. Recently, trimethylamine N-oxide (TMAO) has emerged as a key mediator which provides mechanistic link between gut microbiota and multiple cardiovascular diseases, including HF. Potential intervention strategies which may target this microbiota-driven pathology include dietary modification, prebiotics or probiotics, and selective binders of microbial enzymes or molecules - yet further investigations into their safety and efficacy are warranted.
    Journal of cardiac failure 10/2015; DOI:10.1016/j.cardfail.2015.09.017 · 3.05 Impact Factor

  • JACC: Heart Failure 10/2015; 3(10):777-785. DOI:10.1016/j.jchf.2015.06.006
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    ABSTRACT: High blood pressure, which affects more than 1 billion people worldwide , is a major risk factor for myocardial infarction, stroke and chronic kidney disease. Approximately 9 million deaths each year are attributable to high blood pressure, including >50% of deaths from coronary heart disease and stroke 1,2. High blood pressure is more prevalent in people of East Asian and South Asian ancestry and is a major contributor to their increased risk of stroke and coronary heart disease 3,4. Genome-wide association studies (GWAS) have identified over 50 genetic loci influencing blood pressure in predominantly European populations 5–16. A role for epigenetic mechanisms in blood pressure regulation has also been suggested 17–20. We carried out a GWAS in East Asians and South Asians, as well as Europeans, to seek both cosmopolitan and population-specific genetic effects for five blood pressure phenotypes: systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure, mean arterial pressure (MAP) and hypertension (Supplementary Fig. 1) (ref. 5). We then sought DNA coding and gene regulatory mechanisms, including DNA methylation and gene transcription, to help explain the relationships we observed between sequence variation and blood pressure. RESULTS Genome-wide association and replication testing We used genome-wide association data from 99,994 individuals of East Asian (n = 31,516), European (n = 35,352) and South Asian (n = 33,126) ancestry. Characteristics of the participants and information on the genotyping arrays and imputation are summarized in Supplementary Tables 1–3. Phenotype-specific meta-analysis was carried out separately for East Asian, European and South Asian samples, followed by a meta-analysis across the three ancestral population groups. The trans-ancestry genome-wide association results identified 4,077 variants with P < 1 × 10 −4 against any blood pressure phenotype, distributed among 630 genetic loci. At each locus, we identified the sentinel SNP (the SNP with the lowest P value against any phenotype) and carried out combined analysis with phenotype-specific results from the International Consortium on Blood Pressure (ICBP) GWAS (maximum n = 87,205) (refs. 8,9). This analysis identified 19 previously unreported loci where the sentinel SNP had suggestive evidence for association with blood pressure (P < 1 × 10 −7
    Nature Genetics 09/2015; DOI:10.1038/ng.3405 · 29.35 Impact Factor
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    ABSTRACT: Race has seldomly been reported in the major clinical trials of cardiac resynchronization therapy (CRT). When described, African Americans (AAs) were substantially under-represented. This study sought to compare reverse ventricular remodeling and long-term outcomes in AAs versus European Americans (EAs) with advanced heart failure who underwent CRT. We extracted demographic (including race), clinical, and echocardiographic data on patients with advanced heart failure who underwent CRT with a left ventricular ejection fraction (LVEF) ≤35% and a QRS duration ≥120 ms. Long-term outcomes were compared between AAs and EAs. In patients in whom follow-up echocardiograms were available, improvement in LVEF (defined as an absolute improvement ≥5%) was compared between races. From a cohort of 662 patients, there were 88 AAs and 574 EAs. At a mean follow-up of 5.0 ± 2.5 years, survival rate free of left ventricular assist device (LVAD) and heart transplant was 54.5% for AAs and 53.8% for EAs (log-rank p = 0.997). In multivariate analysis, there was no difference in survival free of heart transplant or LVAD based on race (hazard ratio 1.1 [0.74 to 1.56], p = 0.72, EAs race as referent); 424 patients had a follow-up echocardiogram (55.4% EAs and 64.7% AAs). In multivariate analysis, there was no difference in the incidence of response based on race (1.1 [0.6 to 2.1, p = 0.80], EAs as referent). AAs derive similar benefits with CRT compared with EAs in terms of improvement in LVEF and long-term survival free of LVAD and heart transplant.
    The American journal of cardiology 09/2015; 116(7):1101-5. DOI:10.1016/j.amjcard.2015.07.016 · 3.28 Impact Factor
  • Daniel Li · Jennifer Kirsop · W H Wilson Tang ·
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    ABSTRACT: What we understand about diabetes from decades of genetics research is now being supplemented with exciting new evidence based on a better understanding of how one of the biggest "environmental" factors the body is exposed to is influencing the pathogenesis of disease. The recent discovery that certain dietary nutrients possessing a trimethylamine (TMA) moiety (namely choline/phosphatidylcholine and L-carnitine) participate in the development of atherosclerotic heart disease has renewed attention towards the contributions of gut microbiota in the development of cardiovascular diseases. Collectively, animal and human studies reveal that conversion of these nutrient precursors to trimethylamine N-oxide (TMAO) depends on both microbial composition and host factors, and can be induced by dietary exposures. In addition, circulating TMAO levels are strongly linked to cardiovascular disease risks and various adverse cardio-renal consequences. Our group and others have further demonstrated that circulating TMAO levels are elevated in patients with type 2 diabetes mellitus compared to healthy controls and gut microbiota-dependent phosphatidylcholine metabolism has been implicated in metabolic dysregulation and insulin resistance in animal models. Therefore, preventive strategies to minimize adverse consequences associated with TMAO generation in the diabetic population are warranted.
    Current Diabetes Reports 09/2015; 15(9):634. DOI:10.1007/s11892-015-0634-1 · 3.08 Impact Factor
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    ABSTRACT: Sodium-glucose transporter-2 (SGLT-2) inhibitors have emerged as novel oral glucose-lowering agents for type 2 diabetes. SGLT-2 inhibitors improve glycemic control by blocking sodium-glucose cotransport in the renal proximal tubules, thereby promoting glycosuria. In this review, it is discussed mechanistically how SGLT-2 inhibitors might be particularly relevant to use in patients with or at high risk for heart failure. On a daily base, SGLT-2 inhibitors block ~330–495 mEq sodium reabsorbed in the proximal tubules, although substantial amounts can be reabsorbed more distally in the nephron. Increased sodium offering to the distal nephron is sensed at the macula densa and may attenuate neurohumoral activation, thereby improving salt sensitivity, augmenting diuretic efficacy of loop and thiazide diuretics, and potentiating the native natriuretic peptide system. Whether the favorable profile offered by SGLT-2 inhibitors is renoprotective and whether SGLT-2 inhibition can relieve and/or prevent congestion beyond traditional diuretic drugs warrants further investigation.
    Current Cardiovascular Risk Reports 08/2015; 9(8). DOI:10.1007/s12170-015-0467-0
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    ABSTRACT: Background: Worsening renal function in heart failure may be related to increased venous congestion, decreased cardiac output, or both. Diuretics are universally used in acute decompensated heart failure, but they may be ineffective and may lead to azotemia. We aimed to compare the decongestive properties of a urine output-guided diuretic adjustment and standard therapy for the management of cardiorenal syndrome in acute decompensated heart failure. Methods and results: Data were pooled from subjects randomized to the stepwise pharmacologic care algorithm (SPCA) in the CARRESS-HF trial and those who developed cardiorenal syndrome (rise in creatinine >0.3 mg/dL) in the DOSE-AHF and ROSE-AHF trials. Patients treated with SPCA (n = 94) were compared with patients treated with standard decongestive therapy (SDT) that included intravenous loop diuretic use (DOSE-AHF and ROSE-AHF; n = 107) at the time of cardiorenal syndrome and followed for net fluid balance, weight loss, and changing renal function. The SPCA group had higher degrees of jugular venous pressure (P < .0001) at the time of cardiorenal syndrome. The group that received SPCA had more weight change (-3.4 ± 5.2 lb) and more net fluid loss (1.705 ± 1.417 L) after 24 hours than the SDT group (-0.8 ± 3.4 lb and 0.892 ± 1.395 L, respectively; P < .001 for both) with a slight improvement in renal function (creatinine change -0.1 ± 0.3 vs 0.0 ± 0.3 mg/dL, respectively; P = .03). Conclusions: Compared with SDT, patients who received an intensification of medication therapy for treating persisting congestion had greater net fluid and weight loss without being associated with renal compromise.
    Journal of cardiac failure 08/2015; DOI:10.1016/j.cardfail.2015.07.007 · 3.05 Impact Factor
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    ABSTRACT: Acute decompensated heart failure (ADHF) can be complicated by electrolyte abnormalities, but the major focus has been concentrated on the clinical significance of serum sodium levels. This study sought to determine the prognostic significance of serum chloride levels in relation to serum sodium levels in patients with ADHF. We reviewed 1,318 consecutive patients with chronic heart failure admitted for ADHF to the Cleveland Clinic between July 2008 and December 2013. We also validated our findings in an independent ADHF cohort from the University of Pennsylvania (n = 876). Admission serum chloride levels during hospitalization for ADHF were independently and inversely associated with long-term mortality (hazard ratio [HR] per unit change: 0.94; 95% confidence interval [CI]: 0.92 to 0.95; p < 0.001). After multivariable risk adjustment, admission chloride levels remained independently associated with mortality (HR per unit change: 0.93; 95% CI: 0.90 to 0.97; p < 0.001) in contrast to admission sodium levels, which were no longer significant (p > 0.05). Results were similar in the validation cohort in unadjusted (HR per unit change for mortality risk within 1 year: 0.93; 95% CI: 0.91 to 0.95; p < 0.001) and multivariable risk-adjusted analysis (HR per unit change for mortality risk within 1 year: 0.95; 95% CI: 0.92 to 0.99; p = 0.01). These observations in a contemporary advanced ADHF cohort suggest that serum chloride levels at admission are independently and inversely associated with mortality. The prognostic value of serum sodium in ADHF was diminished compared with chloride. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
    Journal of the American College of Cardiology 08/2015; 66(6):659-66. DOI:10.1016/j.jacc.2015.06.007 · 16.50 Impact Factor

  • Antonio L. Perez · Timothy Engelman · W.H. Wilson Tang ·

  • Yuji Nagatomo · Christine S. Moravec · W. H. Wilson Tang ·

Publication Stats

10k Citations
3,456.97 Total Impact Points


  • 2008-2015
    • Lerner Research Institute
      • Department of Cellular and Molecular Medicine
      Cleveland, Ohio, United States
    • Rede Sarah de Hospitais de Reabilitação
      Brasília, Federal, Brazil
  • 2003-2015
    • Cleveland Clinic
      • • Department of Cell Biology
      • • Department of Cardiovascular Medicine
      • • Department of Cardiology
      Cleveland, Ohio, United States
  • 2014
    • Henry Ford Hospital
      Detroit, Michigan, United States
  • 2013
    • MetroHealth Medical Center
      Cleveland, Ohio, United States
    • London School of Hygiene and Tropical Medicine
      Londinium, England, United Kingdom
  • 2005-2013
    • Case Western Reserve University
      • Division of Cardiovascular Medicine
      Cleveland, Ohio, United States
    • University of Alabama at Birmingham
      • Department of Medicine
      Birmingham, Alabama, United States
  • 2012
    • NCI-Frederick
      Фредерик, Maryland, United States
    • Baylor College of Medicine
      Houston, Texas, United States
    • Cleveland Clinic Laboratories
      Cleveland, Ohio, United States
    • Universiteit Hasselt
      • Faculty of Medicine and Life Sciences
      Flanders, Belgium
  • 2008-2012
    • Metropolitan Heart and Vascular Institute
      Minneapolis, Minnesota, United States
  • 2011
    • Allegheny General Hospital
      Pittsburgh, Pennsylvania, United States
  • 1999-2011
    • Stanford Medicine
      • Division of Cardiovascular Medicine
      Stanford, California, United States
  • 2009
    • University of Western Sydney
      • School of Nursing and Midwifery
      Penrith, New South Wales, Australia
  • 2007
    • VA San Diego Healthcare System
      San Diego, California, United States
    • IST Austria
      Klosterneuberg, Lower Austria, Austria
  • 2004
    • University of North Carolina at Chapel Hill
      North Carolina, United States
    • University of Texas Southwestern Medical Center
      • Department of Internal Medicine
      Dallas, Texas, United States
  • 2001-2004
    • Stanford University
      • Division of Cardiovascular Medicine
      Palo Alto, California, United States