Personalized Cardiovascular Medicine Today

Blaus, Alison; Madabushi, Rajanikanth; Pacanowski, Michael; Rose, Martin; Schuck, Robert N.; Stockbridge, Norman; Unger, Ellis F.

doi:10.1161/circulationaha.114.009761

Cited by 33 publications

(12 citation statements)

References 34 publications

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“…In this way, for example, it is possible to monitor time dependent, infection-induced changes in metabolites due to various strains of pneumonia-causing bacteria, which return to levels associated with health upon resolution of infection ( 13 ). This level of detail could be particularly important for driving efforts in precision medicine for which reliable and reproducible biomarker credentials ( 14 ) are needed for well-informed clinical decision-making and the design of clinical trials ( 15 ).…”

Section: What Is Metabolomics?mentioning

confidence: 99%

Metabolomics and Its Application to Acute Lung Diseases

et al. 2016

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Metabolomics is a rapidly expanding field of systems biology that is gaining significant attention in many areas of biomedical research. Also known as metabonomics, it comprises the analysis of all small molecules or metabolites that are present within an organism or a specific compartment of the body. Metabolite detection and quantification provide a valuable addition to genomics and proteomics and give unique insights into metabolic changes that occur in tangent to alterations in gene and protein activity that are associated with disease. As a novel approach to understanding disease, metabolomics provides a “snapshot” in time of all metabolites present in a biological sample such as whole blood, plasma, serum, urine, and many other specimens that may be obtained from either patients or experimental models. In this article, we review the burgeoning field of metabolomics in its application to acute lung diseases, specifically pneumonia and acute respiratory disease syndrome (ARDS). We also discuss the potential applications of metabolomics for monitoring exposure to aerosolized environmental toxins. Recent reports have suggested that metabolomics analysis using nuclear magnetic resonance (NMR) and mass spectrometry (MS) approaches may provide clinicians with the opportunity to identify new biomarkers that may predict progression to more severe disease, such as sepsis, which kills many patients each year. In addition, metabolomics may provide more detailed phenotyping of patient heterogeneity, which is needed to achieve the goal of precision medicine. However, although several experimental and clinical metabolomics studies have been conducted assessing the application of the science to acute lung diseases, only incremental progress has been made. Specifically, little is known about the metabolic phenotypes of these illnesses. These data are needed to substantiate metabolomics biomarker credentials so that clinicians can employ them for clinical decision-making and investigators can use them to design clinical trials.

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Section: What Is Metabolomics?mentioning

confidence: 99%

Metabolomics and Its Application to Acute Lung Diseases

et al. 2016

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“…In the future, novel methodologies to improve the design of therapeutics research in small populations might include study “enrichment” techniques, whereby genetic or physiological biomarkers are used to enhance study power by enrolling subsets of patients with either: 1) predicted increased treatment effects; or 2) predicted increased risk of adverse effects (31). Computer modeling and simulation, possibly integrated with pharmacogenetics data, might be used in the future to decrease the number of human subjects needed to conduct meaningful therapeutic trials.…”

Section: Future Directionsmentioning

confidence: 99%

2017 ACC/AAP/AHA Health Policy Statement on Opportunities and Challenges in Pediatric Drug Development: Learning From Sildenafil

Sable¹,

Ivy²,

Beekman³

et al. 2017

Journal of the American College of Cardiology

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The STARTS-1 and -2 trials (Sildenafil in Treatment-Naive Children, Aged 1 to 17 Years, With Pulmonary Arterial Hypertension) and subsequent 2012 U.S. Food and Drug Administration (FDA) product labeling for sildenafil use in pediatric patients with pulmonary hypertension highlight many of the challenges to the development and approval of medications for children. This experience served as the impetus for direct collaboration between FDA representatives and the Joint Council on Congenital Heart Disease (JCCHD) (representing the pediatric cardiology leadership of the American College of Cardiology, the American Heart Association, and the American Academy of Pediatrics) to improve communication and realign missions with regard to pediatric drug trials. These discussions led to the joint FDA/JCCHD development of this statement, which describes the current environment and identifies possible future directions for reducing barriers to pediatric drug trials.

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“…Personalized medicine refers to the science and practice of tailoring treatments to the individual characteristics of each patient. 1, 2 In oncology and infectious disease, personalized medicine has enabled major advances in delivering the right intervention to the right patient to improve outcomes. Personalized medicine has yet to be applied to most cardiovascular diseases, including heart failure (HF).…”

Section: Introductionmentioning

confidence: 99%

Aortic Waveform Analysis to Individualize Treatment in Heart Failure

Wohlfahrt

Melenovský

Redfield

et al. 2017

Circ: Heart Failure

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Background Afterload reduction is a cornerstone in the management of patients with heart failure (HF) and reduced ejection fraction (HFrEF). However, arterial load and the effect of HF therapies on afterload might vary between individuals. Tailoring vasoactive medicines to HF patients based upon better understanding of arterial afterload may enable better individualization of therapy. Methods and Results Subjects with HFrEF underwent aggressive titration of vasoactive HF therapies with assessment of central aortic waveforms analyzed using pulse wave, wave separation and arterial reservoir models. Clinical response to treatment was assessed using the 6-minute walk test distance, which increased in 25 subjects and decreased or remained unchanged in 13. Subjects with improvement on therapy displayed higher aortic pressure wave pulsatility (central pulse pressure, reflected pressure wave and reservoir pressure) at study entry compared to subjects without improvement (all p<0.05). Parameters derived by the arterial analysis methods were strongly correlated with one another and displayed similar ability to predict improvement. Aortic pressure pulsatility significantly decreased in subjects with functional improvement, while no change was observed in patients without functional improvement (p for interaction <0.05). These differences in arterial load at baseline and on therapy were not apparent from conventional brachial artery cuff pressure assessments. Conclusions Increased aortic pressure wave pulsatility and greater decrease in pulsatility on treatment are associated with functional improvement in patients with HFrEF receiving aggressive vasodilator titration. These differences are not identifiable using brachial cuff pressures. Central aortic waveform analysis may enable better individualization of vasoactive therapies in chronic HFrEF. Clinical Trial Registration ClinicalTrials.gov; NCT00588692

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Personalized Cardiovascular Medicine Today

Cited by 33 publications

References 34 publications

Metabolomics and Its Application to Acute Lung Diseases

Metabolomics and Its Application to Acute Lung Diseases

2017 ACC/AAP/AHA Health Policy Statement on Opportunities and Challenges in Pediatric Drug Development: Learning From Sildenafil

Aortic Waveform Analysis to Individualize Treatment in Heart Failure

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