M R Bristow

University of Colorado, Denver, Colorado, United States

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Publications (439)2737.61 Total impact

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    ABSTRACT: Rationale: H2RA use is common and may act directly on the heart through myocardial H2 receptors or indirectly through changes in pulmonary vascular resistance. Objective: To determine the relationship between histamine H2 receptor antagonist (H2RA) use and right ventricular (RV) morphology. Methods: We studied 4,124 participants in the Multi-Ethnic Study of Atherosclerosis without overt cardiovascular disease who had magnetic resonance imaging (MRI) assessment of RV morphology and ascertainment of medication use. Multivariable linear regression estimated cross-sectional associations between H2RA use and RV morphology after adjusting for demographics, anthropometrics, smoking status, diabetes mellitus and hypertension. Further adjustment for co-medication use, left ventricular (LV) parameters, lung structure and function, renal function, or inflammatory markers were considered in separate models. Analyses in a sub-cohort restricted to H2RA or proton pump inhibitor (PPI) users accounted for confounding by the indication of gastroesophageal reflux disease. Measurements and Main Results: H2RA use was associated with lower RV mass (-0.7 g, 95% confidence interval (CI): -1.2 to -0.2 g, p=0.004) and smaller RV end-diastolic volume (EDV) (-4.2 mL, 95% CI: -7.2 to -1.2 mL, p=0.006). This relationship was unchanged with adjustment for co-medication use, lung structure and function, renal function, and inflammation. The relationship with RV mass was independent of LV mass. Results were similar in a smaller sub-cohort restricted to PPI and H2RA users. Conclusion: H2RA use was associated with lower RV mass and smaller RVEDV. This finding is novel. Additional study of histamine and H2 receptors in cardiopulmonary diseases affecting the RV may have direct clinical relevance.
    Annals of the American Thoracic Society. 10/2014;
  • Michael R Bristow
    JACC. Heart failure. 09/2014;
  • Journal of cardiac failure. 08/2014; 20(8S):S82.
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    ABSTRACT: Atrial Fibrillation and heart failure with reduced left ventricular ejection fraction have interrelated pathophysiologies. New onset atrial fibrillation in heart failure patients has been associated with increased mortality, but has not been definitively related to clinical heart failure progression.
    The American journal of medicine. 06/2014;
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    ABSTRACT: This study assessed the impact of bucindolol, a beta-blocker/sympatholytic agent, on the development of atrial fibrillation (AF) in advanced chronic heart failure with reduced left ventricular ejection fraction (HFREF) patients enrolled in the BEST (Beta-Blocker Evaluation of Survival Trial). β-Blockers have modest efficacy for AF prevention in HFREF patients. Bucindolol's effects on HF and ventricular arrhythmic endpoints are genetically modulated by β1- and α2c-adrenergic receptor (AR) polymorphisms that can be used to subdivide HFREF populations into those with bucindolol effectiveness levels that are enhanced, unchanged, or lost. BEST enrolled 2,708 New York Heart Association (NYHA) class III to IV HFREF patients. A substudy in which 1,040 patients' DNA was genotyped for the β1-AR position 389 Arg/Gly and the α2c322-325 wild type (Wt)/deletion (Del) polymorphisms, and new-onset AF was assessed from adverse event case report forms or electrocardiograms at baseline and at 3 and 12 months. In the entire cohort, bucindolol reduced the rate of new-onset AF compared to placebo by 41% (hazard ratio [HR]: 0.59 [95% confidence interval (CI): 0.44 to 0.79], p = 0.0004). In the 493 β1389 arginine homozygotes (Arg/Arg) in the DNA substudy, bucindolol reduced new-onset AF by 74% (HR: 0.26 [95% CI: 0.12 to 0.57]), with no effect in β1389 Gly carriers (HR: 1.01 [95% CI: 0.56 to 1.84], interaction test = 0.008). When β1389 Gly carriers were subdivided by α2c Wt homozygotes (n = 413, HR: 0.94 [95% CI: 0.48 to 1.82], p = 0.84) or Del variant carriers (n = 134, HR: 1.33 [95% CI: 0.32 to 5.64], p = 0.70), there was a positive interaction test (p = 0.016) when analyzed with β1389 Arg homozygotes. Bucindolol prevented new-onset AF; β1 and α2c polymorphisms predicted therapeutic response; and the 47% of patients who were β1389 Arg homozygotes had an enhanced effect size of 74%. (Beta-Blocker Evaluation in Survival Trial [BEST]; NCT00000560).
    JACC. Heart failure. 08/2013; 1(4):338-344.
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    ABSTRACT: The complexity of standard medical treatment for heart failure is growing, and such therapy typically involves 5 or more different medications. Given these pressures, there is increasing interest in harnessing cardiovascular biomarkers for clinical application to more effectively guide diagnosis, risk stratification, and therapy. It may be possible to realize an era of personalized medicine for heart failure treatment in which therapy is optimized and costs are controlled. The direct mechanistic coupling of biologic processes and therapies achieved in cancer treatment remains elusive in heart failure. Recent clinical trials and meta-analyses of biomarkers in heart failure have produced conflicting evidence. In this article, which comprises a summary of discussions from the Global Cardiovascular Clinical Trialists Forum held in Paris, France, we offer a brief overview of the background and rationale for biomarker testing in heart failure, describe opportunities and challenges from a regulatory perspective, and summarize current positions from government agencies in the United States and European Union.
    Journal of cardiac failure 08/2013; 19(8):592-9. · 3.25 Impact Factor
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    ABSTRACT: BACKGROUND: -Patients with heart failure and coronary artery disease often undergo coronary artery bypass grafting (CABG) but assessment of the risk of an adverse outcome in these patients is difficult. To evaluate the ability of biomarkers to contribute independent prognostic information in these patients, we measured levels in patients enrolled in the Biomarker Sub-studies of the Surgical Treatment for Ischemic Heart Failure (STICH) trials. Patients in STICH Hypothesis 1 were randomized to medical therapy or CABG whereas those in STICH Hypothesis 2 were randomized to CABG or CABG with left ventricular reconstruction. METHODS AND RESULTS: -In sub-study patients assigned to STICH Hypothesis 1 (n=606), plasma levels of sTNFR-1 and BNP were highly predictive of the primary outcome variable of mortality by univariate analysis (BNP χ(2)=40.6; p<0.0001: sTNFR-1 χ(2)=38,9; p<0.0001). When considered in the context of multivariable analysis, both BNP and sTNFR-1 contributed independent prognostic information beyond the information provided by a large array of clinical factors independent of treatment assignment. Consistent results were seen when assessing the predictive value of BNP and sTNFR-1 in patients assigned to STICH Hypothesis 2 (n=626). Both plasma levels of BNP (χ(2)=30.3) and sTNFR-1 (χ(2)=45.5) were highly predictive in univariate analysis (p<0.0001) as well as in multivariable analysis for the primary endpoint of death or cardiac hospitalization. In multivariable analysis, the prognostic information contributed by BNP (χ(2)=6.0; p=0.049) and sTNFR-1 (χ(2)=8.8; p=0.003) remained statistically significant even after accounting for other clinical information. Although the biomarkers added little discriminatory improvement to the clinical factors (increase in c-index ≤ 0.1), Net Reclassification Improvement (NRI) for the primary endpoints was 0.29 for BNP and 0.21 for sTNFR-1in the Hypothesis 1 cohort, and 0.15 for BNP and 0.30 for sTNFR-1 in the Hypothesis 2 cohort, reflecting important predictive improvement. CONCLUSIONS: -Elevated levels of sTNFR-1 and BNP are strongly associated with outcomes, independent of therapy, in two large and independent studies, thus providing important cross-validation for the prognostic importance of these two biomarkers.
    Circulation Heart Failure 04/2013; · 6.68 Impact Factor
  • Michael R. Bristow, Ryan G. Aleong
    JACC: Heart Failure. 02/2013; 1(1):29–30.
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    ABSTRACT: BACKGROUND: -In patients with chronic heart failure and reduced left ventricular ejection fraction (HFREF) β-blockers prevent cardiac arrhythmias, including ventricular tachycardia/fibrillation (VT/VF). We hypothesized that prevention of ventricular arrhythmias by the β-blocker/sympatholytic agent bucindolol is influenced by genetic variation in adrenergic receptors (ARs). METHODS AND RESULTS: -From a substudy of the β-Blocker Evaluation of Survival Trial (BEST, n = 1040), we identified those with the high functioning 389Arg vs. the lower function 389Gly β(1) adrenergic receptor (AR) variant, and the loss of function (α2C)322-325 AR deletion vs. the 322-325 wild type (Wt)/deletion (Del) variant. VT/VF was recorded on case report forms as an adverse event. There were 493 Arg 389 β(1) receptor homozygotes (β(1)389 Arg/Arg) vs. 547 Gly389 carriers and 207 (α2C)322-325 Del carriers vs. 833 homozygous Wts ((α2C)322-325 Wt/Wt). In all genotypes bucindolol was associated with a lower incidence of VT/VF (subhazard ratio (SHR) 0.42 (0.27, 0.64), P=0.00006). Bucindolol reduced VT/VF in β(1)389 Arg homozygotes (SHR 0.26 (0.14, 0.50), P=0.00005) but not in β(1)389 Gly carriers (SHR 0.60 (0.34, 1.07), P=0.09). For genotype combinations, the (α2C)322-325 polymorphism altered the VT/VF bucindolol response in β(1)389 Gly carriers, with (α2C) Del genotypes associated with complete efficacy loss. A test of interaction was statistically significant (P=0.028) for treatment group and a β(1)389/(α2C)322-325 three genotype construct, effectively identifying patients who exhibited enhanced response, no substantial response modification and loss of response. CONCLUSIONS: -Bucindolol prevents VT/VF in HFREF subjects, and this effect is modulated by β(1)389 Arg/Gly and (α2C)322-325 Wt/Del AR polymorphisms.
    Circulation Arrhythmia and Electrophysiology 12/2012; · 5.95 Impact Factor
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    ABSTRACT: AIMS: There is little evidence of beta-blocker treatment benefit in patients with heart failure and reduced left ventricular ejection fraction (HFREF) and atrial fibrillation (AF). We investigated the effects of bucindolol in HFREF patients with AF enrolled in the Beta-blocker Evaluation of Survival Trial (BEST). METHODS AND RESULTS: A post-hoc analysis of patients in BEST with and without AF was performed to estimate the effect of bucindolol on mortality and hospitalization. Patients were also evaluated for treatment effects on heart rate and the influence of beta(1)-adrenergic receptor position 389 (β(1)389) arginine (Arg) vs. glycine (Gly) genotypes. In the 303/2708 patients in AF, patients receiving bucindolol were more likely to achieve a resting heart rate ≤80 b.p.m. at 3 months (P < 0.005) in the absence of treatment-limiting bradycardia. In AF patients and sinus rhythm (SR) patients who achieved a resting heart rate ≤80 b.p.m., there were beneficial treatment effects on cardiovascular mortality/cardiovascular hospitalization [hazard ratio (HR) 0.61, P = 0.025, and 0.79, P = 0.002]. Without achieving a resting heart rate ≤80 b.p.m., there were no treatment effects on events in either group. β(1)389-Arg/Arg AF patients had nominally significant reductions in all-cause mortality/HF hospitalization and cardiovascular mortality/hospitalization with bucindolol (HR 0.23, P = 0.037 and 0.28, P = 0.039), whereas Gly carriers did not. There was no evidence of diminished heart rate response in β(1)389-Arg homozygotes. CONCLUSION: In HFREF patients with AF, bucindolol was associated with reductions in composite HF endpoints in those who achieved a resting heart rate ≤80 b.p.m. and nominally in those with the β(1)389-Arg homozygous genotype.
    European Journal of Heart Failure 12/2012; · 5.25 Impact Factor
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    ABSTRACT: Background Pharmacogenetics involves complex interactions of gene products affecting pharmacodynamics and pharmacokinetics, but there is little information on the interaction of multiple genetic modifiers of drug response. Bucindolol is a β-blocker/sympatholytic agent whose efficacy is modulated by polymorphisms in the primary target (β1 adrenergic receptor [AR] Arg389 Gly on cardiac myocytes) and a secondary target modifier (α2C AR Ins [wild-type (Wt)] 322–325 deletion [Del] on cardiac adrenergic neurons). The major allele homozygotes and minor allele carriers of each polymorphism are respectively associated with efficacy enhancement and loss, creating the possibility for genotype combination interactions that can be measured by clinical trial methodology. Methodology In a 1,040 patient substudy of a bucindolol vs. placebo heart failure clinical trial, we tested the hypothesis that combinations of β1389 and α2C322–325 polymorphisms are additive for both efficacy enhancement and loss. Additionally, norepinephrine (NE) affinity for β1389 AR variants was measured in human explanted left ventricles. Principal Findings The combination of β1389 Arg+α2C322–325 Wt major allele homozygotes (47% of the trial population) was non-additive for efficacy enhancement across six clinical endpoints, with an average efficacy increase of 1.70-fold vs. 2.32-fold in β1389 Arg homozygotes+α2C322–325 Del minor allele carriers. In contrast, the minor allele carrier combination (13% subset) exhibited additive efficacy loss. These disparate effects are likely due to the higher proportion (42% vs. 8.7%, P = 0.009) of high-affinity NE binding sites in β1389 Arg vs. Gly ARs, which converts α2CDel minor allele-associated NE lowering from a therapeutic liability to a benefit. Conclusions On combination, the two sets of AR polymorphisms 1) influenced bucindolol efficacy seemingly unpredictably but consistent with their pharmacologic interactions, and 2) identified subpopulations with enhanced (β1389 Arg homozygotes), intermediate (β1389 Gly carriers+α2C322–325 Wt homozygotes), and no (β1389 Gly carriers+α2C322–325 Del carriers) efficacy.
    PLoS ONE 10/2012; 7(10). · 3.53 Impact Factor
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    ABSTRACT: Elevation in plasma activity of von Willebrand factor (vWF) reflects endothelial dysfunction and predicts death in pulmonary arterial hypertension. Higher vWF activity is also associated with a lower right ventricular (RV) ejection fraction in pulmonary arterial hypertension. Little is known about the relation between vWF and RV structure and function in adults without cardiovascular disease. The present investigation included 1,976 participants with magnetic resonance imaging assessment of RV structure and function and measurement of vWF activity from the Multi-Ethnic Study of Atherosclerosis. Multivariable linear regression was used to estimate the associations between vWF activity and measures of RV structure and function after adjusting for demographics, anthropometrics, smoking, diabetes mellitus, hypertension, and the corresponding left ventricular parameter. The average vWF activity was 140.7 ± 57.2%. Elevated vWF activity was independently associated with lower RV mass, RV end-diastolic volume, and RV stroke volume in models with and without adjustment for the corresponding left ventricular parameter (all p values <0.05). There was no association observed between vWF activity and the RV ejection fraction. In conclusion, higher vWF activity is associated with lower RV mass, RV end-diastolic volume, and RV stroke volume. These associations are independent of common cardiovascular risk factors and left ventricular morphologic changes.
    The American journal of cardiology 09/2012; · 3.58 Impact Factor
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    ABSTRACT: Changes in right ventricular (RV) morphology are associated with morbidity and mortality in heart and lung disease. We examined the association of abnormal RV structure and function with the risk of heart failure or cardiovascular death in a population-based multiethnic sample free of clinical cardiovascular disease at baseline. The Multi-Ethnic Study of Atherosclerosis (MESA) performed cardiac magnetic resonance imaging on 5098 participants between 2000 and 2002 with follow-up for incident heart failure and cardiovascular death ("death") until January 2008. RV volumes and mass were available for 4204 participants. The study sample (n=4144) was 61.4±10.1 years old and 47.6% male. The presence of RV hypertrophy (increased RV mass) was associated with more than twice the risk of heart failure or death after adjustment for demographics, body mass index, education, C-reactive protein level, hypertension, and smoking status (hazard ratio, 2.52; 95% confidence interval, 1.55-4.10; P<0.001) and a doubling (or more) of risk with left ventricular mass at the mean value or lower (P for interaction=0.05). RV hypertrophy was associated with the risk of heart failure or death in a multiethnic population free of clinical cardiovascular disease at baseline.
    Circulation 08/2012; 126(14):1681-8. · 15.20 Impact Factor
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    ABSTRACT: The pulmonary vasculature is an important site of renin-angiotensin metabolism. While angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (collectively AIABs) have a role in left ventricular (LV) disease, the impact of AIABs on right ventricular (RV) function is unknown. AIAB use was determined by medication inventory during the Multi-Ethnic Study of Atherosclerosis baseline examination. RV measures were obtained via cardiac magnetic resonance imaging. The relationship between AIAB use and RV measures was assessed using multivariable linear regression, stratified by race/ethnicity, and adjusted for multiple covariates. AIAB use was associated with lower RV mass (-0.7 g, 95% confidence interval [CI] -1.3 to -0.1, P=0.03) in African Americans (N=1012) after adjustment for multiple covariates including LV mass. Among Caucasians (N=1591), AIAB use was associated with larger RV end-diastolic volume (3.7 mL, 95% CI 0.7-6.8, P=0.02) after adjustment for LV volume. No significant associations were seen between AIAB use and other RV measures or in Hispanic or Chinese American participants. AIAB use was associated with RV morphology in a race-specific and LV-independent manner, suggesting the renin-angiotensin system may play a unique role in RV structure and function. The use of AIABs in those with RV dysfunction warrants further study.
    Pulmonary circulation. 07/2012; 2(3):379-86.
  • Michael R Bristow
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    ABSTRACT: Pharmacogenetic drug development represents an ideal approach to enhance a drug's response rate in a disease indication cohort, thereby increasing the therapeutic index. The most straightforward way to develop a pharmacogenetically targeted drug is to identify a functionally important genetic variant in the drug's target(s), or in a target modifier. There are two general ways to detect such genetic variation, the candidate gene variant hypothesis testing approach, and genome wide scanning "hypothesis free" methods. In order to impact drug development either approach needs to be implemented early in the drug development process, with the candidate strategy having the advantage that it can be introduced earlier, during preclinical development. Contrary to conventional wisdom, a pharmacogenetic approach does not increase the overall efficiency of drug development, because the required additional genetic and biologic function discovery work will be layered onto standard regulatory steps. However, identification of a hyper-responsive subpopulation by a genetic biomarker does increase the chance of success in Phase 3, which may lower the cost of pivotal trials. Perhaps most importantly from a commercial standpoint, pharmacogenetics use patents, typically submitted relatively late in the development process, can greatly extend a drug's exclusivity period. This will recoup the extra cost inherent to pharmacogenetic drug development, and increase the product's return on investment by providing a longer period for branded exclusivity. Most importantly, pharmacogenetic targeting will result in a therapeutic agent with a greater therapeutic index and a better pharmacoeconomic profile than would be possible with pan-genetic, entire cohort positioning.
    Pharmacology [?] Therapeutics 04/2012; 134(1):107-15. · 7.79 Impact Factor
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    ABSTRACT: BACKGROUND: Heart failure patients with reduced ejection fraction (HFREF) are heterogenous, and our ability to identify patients likely to respond to therapy is limited. We present a method of identifying disease subtypes using high-dimensional clinical phenotyping and latent class analysis that may be useful in personalizing prognosis and treatment in HFREF. METHODS: A total of 1121 patients with nonischemic HFREF from the β-blocker Evaluation of Survival Trial were categorized according to 27 clinical features. Latent class analysis was used to generate two latent class models, LCM A and B, to identify HFREF subtypes. LCM A consisted of features associated with HF pathogenesis, whereas LCM B consisted of markers of HF progression and severity. The Seattle Heart Failure Model (SHFM) Score was also calculated for all patients. Mortality, improvement in left ventricular ejection fraction (LVEF) defined as an increase in LVEF ≥5% and a final LVEF of 35% after 12 months, and effect of bucindolol on both outcomes were compared across HFREF subtypes. Performance of models that included a combination of LCM subtypes and SHFM scores towards predicting mortality and LVEF response was estimated and subsequently validated using leave-one-out cross-validation and data from the Multicenter Oral Carvedilol Heart Failure Assessment Trial. RESULTS: A total of 6 subtypes were identified using LCM A and 5 subtypes using LCM B. Several subtypes resembled familiar clinical phenotypes. Prognosis, improvement in LVEF, and the effect of bucindolol treatment differed significantly between subtypes. Prediction improved with addition of both latent class models to SHFM for both 1-year mortality and LVEF response outcomes. CONCLUSIONS: The combination of high-dimensional phenotyping and latent class analysis identifies subtypes of HFREF with implications for prognosis and response to specific therapies that may provide insight into mechanisms of disease. These subtypes may facilitate development of personalized treatment plans.
    PLoS ONE 01/2012; 7(11):e48184. · 3.53 Impact Factor
  • Michael R Bristow
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    ABSTRACT: Despite the absence of a systematic development plan, β-blockers have reached the top tier of medical therapies for chronic heart failure. The successful outcome was due to the many dedicated investigators who produced, over a 30-year period, increasing evidence that β-blocking agents should or actually did improve the natural history of dilated cardiomyopathies and heart failure. It took 20 years for supportive evidence to become undeniable, at which time in 1993 the formidable drug development resources of large pharmaceutical companies were deployed into Phase 3 trials. Success then came relatively quickly, and within 8 years multiple agents were on the market in the United States and Europe. Importantly, there is ample room to improve antiadrenergic therapy, through novel approaches exploiting the nuances of receptor biology and/or intracellular signaling, as well as through pharmacogenetic targeting.
    Circulation Research 10/2011; 109(10):1176-94. · 11.86 Impact Factor
  • J David Port, Michael R Bristow
    Circulation Research 10/2011; 109(9):982-3. · 11.86 Impact Factor
  • Mona Fiuzat, Michael R Bristow
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    ABSTRACT: There is ongoing research into potential pharmacogenetic targets in heart failure. Several challenges exist despite the potential benefits, and questions remain on the level of evidence needed to support product approval or labeling. High annual mortality, high morbidity, and heterogeneity of response to treatment underscore the need for predictability of response in this patient population. Although prime time testing and application of pharmacogenetics is not currently being used in heart failure, we believe this treatment approach is not too distant. The data are supportive, and further research is warranted to strengthen the approach.
    Heart Failure Clinics 10/2011; 7(4):553-9.
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    ABSTRACT: Several studies in humans or transgenic animals have reported that the 389 Arg or Gly polymorphic variation of the β1-adrenergic receptor (AR) is associated with differential responses to beta-blocker therapy and/or myocardial disease progression. Analysis of changes in gene expression is an important means of defining molecular differences associated with structural or functional phenotypic variations. To determine if structural and functional myocardial phenotypic differences between β1389 Arg vs. Gly transgenic overexpressors are associated with qualitative and/or quantitative differences in gene expression, a comprehensive analysis of mRNAs and miRNAs expressed in the hearts of 3 and 6-8 mo old β1-Arg389 and β1-Gly389 overexpressor transgenic mice was performed. Changes in mRNA and miRNA expression were analyzed by arrays and partially confirmed by RT-qPCR. Bioinformatic analysis demonstrated that several genes, including those involved in PKA and CaMK signaling pathways, are regulated in a temporal- or phenotype-specific manner. Furthermore, expression signature analyses indicated that miRNAs have the potential to target expression of a number of genes involved in multiple cardiomyopathy-related pathways, and changes in miRNA expression can precede the onset of disease. Differences in gene expression between β1-Arg389 and β1-Gly389 transgenic mice are largely quantitative rather than qualitative and are associated with the development of cardiomyopathy in a time-dependent manner. Chronic β1-AR overdrive results in increased expression of components of the CaMK pathway, with correspondingly decreased levels of components of the PKA pathway. Based on the temporal and genotype-specific pattern of miRNA expression, miRNAs are likely to be important predictors of disease states, especially when miRNA expression is paired with mRNA expression, and that miRNA/mRNA expression signatures have the potential to be useful in determining the underlying risk associated with cardiac disease progression.
    Physiological Genomics 09/2011; 43(23):1294-306. · 2.81 Impact Factor

Publication Stats

22k Citations
2,737.61 Total Impact Points


  • 1992–2014
    • University of Colorado
      • • Division of Cardiology
      • • Division of Medical Oncology
      • • Department of Medicine
      Denver, Colorado, United States
  • 2011–2013
    • Duke University Medical Center
      • Division of Cardiology
      Durham, North Carolina, United States
    • Hospital of the University of Pennsylvania
      Philadelphia, Pennsylvania, United States
  • 2012
    • University of Washington Seattle
      • Division of Pulmonary and Critical Care Medicine
      Seattle, WA, United States
    • Alpert Medical School - Brown University
      Providence, Rhode Island, United States
  • 2010
    • Columbia University
      • Department of Medicine
      New York City, NY, United States
  • 2009
    • University of Southern California
      • Keck School of Medicine
      Los Angeles, California, United States
    • Minneapolis Heart Institute
      Minneapolis, Minnesota, United States
    • Minneapolis Veterans Affairs Hospital
      Minneapolis, Minnesota, United States
    • Lehigh Valley Health Network
      Allentown, Pennsylvania, United States
    • Università degli Studi di Brescia
      Brescia, Lombardy, Italy
  • 2006–2009
    • U.S. Department of Veterans Affairs
      Washington, Washington, D.C., United States
    • CUNY Graduate Center
      New York City, New York, United States
    • University of Maryland, Baltimore
      • Department of Medicine
      Baltimore, MD, United States
  • 1987–2009
    • University of Utah
      • Division of Cardiology
      Salt Lake City, UT, United States
  • 2008
    • San Francisco VA Medical Center
      San Francisco, California, United States
  • 2007
    • Wayne State University
      Detroit, Michigan, United States
  • 2005
    • Baylor College of Medicine
      • Winters Center for Heart Failure Research
      Houston, TX, United States
    • The Ohio State University
      • Division of Medical Oncology
      Columbus, OH, United States
  • 2004
    • Colorado College
      Colorado Springs, Colorado, United States
  • 2003–2004
    • University of Colorado at Boulder
      • Department of Molecular, Cellular, and Developmental Biology (MCDB)
      Boulder, CO, United States
    • National Heart, Lung, and Blood Institute
      Maryland, United States
  • 1995–2001
    • University of Texas Southwestern Medical Center
      • • Department of Internal Medicine
      • • Department of Pediatrics
      Dallas, TX, United States
    • Montreal Heart Institute
      Montréal, Quebec, Canada
  • 1998
    • Rush University Medical Center
      • Section of Cardiology
      United States
  • 1996
    • University of Colorado Hospital
      • Division of Cardiology
      Denver, Colorado, United States
  • 1983–1995
    • Stanford University
      • • Department of Medicine
      • • Department of Pathology
      Stanford, CA, United States
  • 1988–1994
    • Johns Hopkins University
      • Department of Medicine
      Baltimore, Maryland, United States
  • 1989–1991
    • Salt Lake City Community College
      Salt Lake City, Utah, United States
    • University of Duisburg-Essen
      Essen, North Rhine-Westphalia, Germany
  • 1980–1985
    • Stanford Medicine
      Stanford, California, United States