Publications by authors named "Sophia Airhart"

13 Publications

  • Page 1 of 1

Assessing hemodynamic response to submaximal exercise in pulmonary arterial hypertension patients using an implantable hemodynamic monitor.

J Heart Lung Transplant 2021 06 5;40(6):430-434. Epub 2021 Feb 5.

Division of Cardiovascular Diseases, The Ohio State University, Columbus, Ohio.

Pulmonary arterial hypertension (PAH) is a chronic, progressive disease that is incurable, even with effective therapy. Long-term outcome in PAH is best preserved by targeting hemodynamic improvements to reduce risk of subsequent right ventricular (RV) failure. Methods that can assess RV adaptation to stress have important implications to better understand an individual's physiology and may play a pivotal role in guiding therapy in PAH. In this novel pilot study, we evaluate the feasibility of monitoring hemodynamic response to 6-minute walk distance in patients with PAH using the CardioMEMS HF System.
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http://dx.doi.org/10.1016/j.healun.2021.01.1964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169534PMC
June 2021

Boosting NAD level suppresses inflammatory activation of PBMCs in heart failure.

J Clin Invest 2020 11;130(11):6054-6063

Mitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine and.

BACKGROUNDWhile mitochondria play an important role in innate immunity, the relationship between mitochondrial dysfunction and inflammation in heart failure (HF) is poorly understood. In this study we aimed to investigate the mechanistic link between mitochondrial dysfunction and inflammatory activation in peripheral blood mononuclear cells (PBMCs), and the potential antiinflammatory effect of boosting the NAD level.METHODSWe compared the PBMC mitochondrial respiration of 19 hospitalized patients with stage D HF with that of 19 healthy participants. We then created an in vitro model of sterile inflammation by treating healthy PBMCs with mitochondrial damage-associated molecular patterns (MitoDAMPs) isolated from human heart tissue. Last, we enrolled patients with stage D HF and sampled their blood before and after taking 5 to 9 days of oral nicotinamide riboside (NR), a NAD precursor.RESULTSWe demonstrated that HF is associated with both reduced respiratory capacity and elevated proinflammatory cytokine gene expressions. In our in vitro model, MitoDAMP-treated PBMCs secreted IL-6 that impaired mitochondrial respiration by reducing complex I activity. Last, oral NR administration enhanced PBMC respiration and reduced proinflammatory cytokine gene expression in 4 subjects with HF.CONCLUSIONThese findings suggest that systemic inflammation in patients with HF is causally linked to mitochondrial function of the PBMCs. Increasing NAD levels may have the potential to improve mitochondrial respiration and attenuate proinflammatory activation of PBMCs in HF.TRIAL REGISTRATIONClinicalTrials.gov NCT03727646.FUNDINGThis study was funded by the NIH, the University of Washington, and the American Heart Association.
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http://dx.doi.org/10.1172/JCI138538DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598081PMC
November 2020

Clinical implications of idiopathic pulmonary arterial hypertension phenotypes defined by cluster analysis.

J Heart Lung Transplant 2020 04 21;39(4):310-320. Epub 2020 Jan 21.

Department of Cardiovascular and Respiratory Science, Sapienza University of Rome, Rome, Italy.

Background: >Despite advances in drug development, life expectancy in idiopathic pulmonary arterial hypertension (IPAH) remains unacceptable. Contemporary IPAH characterization is based on criteria that may not adequately capture disease heterogeneity and may be proposed as a possible explanation for why patient outcome is still unfavorable. The aim of this study was to apply cluster analysis to improve phenotyping of patients with IPAH and analyze long-term clinical outcome of derived clusters.

Methods: Patients with IPAH from 2 referral centers (n = 252) were evaluated with clinical, hemodynamic, and echocardiographic assessment and cardiopulmonary exercise test. Patients were classified according to cluster analysis and followed for clinical worsening occurrence.

Results: The cluster analysis identified 4 IPAH phenotypes. Cluster 1 was characterized by young patients, mild pulmonary hypertension (PH), mild right ventricular (RV) dilation and high oxygen (O) pulse; Cluster 2 by severe PH and RV dilation and high O pulse; and Cluster 3 by male patients, severe PH and RV dilation, and low O pulse. Cluster 4 patients were older and overweight, with mild PH and RV dilation and low O pulse. After a mean follow-up of 995 ± 623 days, 123 (48.8%) patients had clinical worsening. Cluster 1 patients presented the best prognosis, whereas Cluster 3 had the highest rates of clinical worsening. Compared with Cluster 1, risk of clinical worsening ranged from 4.12 (confidence interval [CI] 1.43-11.92; p = 0.009) for Cluster 4 to 7.38 (CI 2.80-19.40) for Cluster 2 and 13.8 (CI 5.60-34.0; p = 0.0001) for Cluster 3.

Conclusions: Cluster analysis of clinical variables identified 4 distinct phenotypes of IPAH. Our findings underscore the high degree of disease heterogeneity that exists within patients with IPAH and the need for advanced clinical testing to define phenotypes to improve treatment strategy decision-making. CONDENSED ABSTRACT Idiopathic pulmonary arterial hypertension (IPAH) characterization is based on criteria that may not adequately capture disease heterogeneity. The aim of this study was to apply cluster analysis to improve phenotyping of IPAH. Patients with IPAH (n = 252) were evaluated with clinical, hemodynamic, and echocardiographic assessment and cardiopulmonary exercise test. Within the umbrella category of IPAH, it was the combination of mean pulmonary arterial pressure, right ventricular size, and oxygen pulse that further stratified patients into novel IPAH phenotypes that significantly associate with clinical worsening. These findings underscore the need for novel multidimensional IPAH phenotyping for improved patient care and trial quality.
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http://dx.doi.org/10.1016/j.healun.2019.12.012DOI Listing
April 2020

Monitoring Pulmonary Arterial Hypertension Using an Implantable Hemodynamic Sensor.

Chest 2019 12 29;156(6):1176-1186. Epub 2019 Jun 29.

Cardiovascular Institute, Allegheny General Hospital, Pittsburgh, PA.

Background: Pulmonary arterial hypertension (PAH) is a chronic disease that ultimately progresses to right-sided heart failure (HF) and death. Close monitoring of pulmonary artery pressure (PAP) and right ventricular (RV) function allows clinicians to appropriately guide therapy. However, the burden of commonly used methods to assess RV hemodynamics, such as right heart catheterization, precludes frequent monitoring. The CardioMEMS HF System (Abbott) is an ambulatory implantable hemodynamic monitor, previously only used in patients with New York Heart Association (NYHA) class III HF. In this study, we evaluate the feasibility and early safety of monitoring patients with PAH and right-sided HF using the CardioMEMS HF System.

Methods: The CardioMEMS HF sensors were implanted in 26 patients with PAH with NYHA class III or IV right-sided HF (51.3 ± 18.3 years of age, 92% women, 81% NYHA class III). PAH therapy was tracked using a minimum of weekly reviews of CardioMEMS HF daily hemodynamic measurements. Safety, functional response, and hemodynamic response were tracked up to 4 years with in-clinic follow-ups.

Results: The CardioMEMS HF System was safely used to monitor PAH therapy, with no device-related serious adverse events observed and a single preimplant serious adverse event. Significant PAP reduction and cardiac output elevation were observed as early as 1 month postimplant using trends of CardioMEMS HF data, coupled with significant NYHA class and quality of life improvements within 1 year.

Conclusions: The CardioMEMS HF System provided useful information to monitor PAH therapy, and demonstrated short- and long-term safety. Larger clinical trials are needed before its widespread use to guide therapy in patients with severe PAH with right-sided HF.
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http://dx.doi.org/10.1016/j.chest.2019.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904858PMC
December 2019

Use of an implantable wireless pulmonary pressure monitor during transition of therapy in pulmonary arterial hypertension.

J Heart Lung Transplant 2019 02 24;38(2):227-230. Epub 2018 Nov 24.

Cardiovascular Institute, Allegheny General Hospital, Pittsburgh, Pennsylvania, USA.

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http://dx.doi.org/10.1016/j.healun.2018.11.011DOI Listing
February 2019

Health Status Benefits of Successful Chronic Total Occlusion Revascularization Across the Spectrum of Left Ventricular Function: Insights From the OPEN-CTO Registry.

JACC Cardiovasc Interv 2018 11;11(22):2276-2283

University of Washington, Seattle, Washington. Electronic address:

Objectives: This study sought to describe the association between chronic total occlusion (CTO) revascularization (CTO percutaneous coronary intervention [PCI]) and health status in patients with and without cardiomyopathy.

Background: Prior PCI trials for cardiomyopathy have excluded CTO patients. Whether patients with reduced left ventricular ejection fraction (LVEF) receive similar health status benefit from CTO-PCI compared with patients with normal LVEF is unclear.

Methods: We assessed health status change, using the Seattle Angina Questionnaire (SAQ) Summary, SAQ Angina Frequency, and Rose Dyspnea Scale scores, among patients undergoing successful CTO PCI in the OPEN-CTO (Outcomes, Patient Health Status, and Efficiency in Chronic Total Occlusion) Registry. Participants were classified by LVEF (normal, ≥50%; mild-moderate, 30% to 49%; and severe, <30%), with higher SAQ and lower Rose Dyspnea Scale scores indicating better health status. Differences in 1-year outcomes were compared using hierarchical multivariable regression.

Results: Of 762 patients, 506 (66.4%), 193 (25.3%), and 63 (8.3%) had normal, mild-moderate, and severely reduced LVEF. SAQ Summary score improvements were observed in each group (27.1 ± 20.4, 26.7 ± 21.2, and 20.3 ± 18.1, respectively). Compared with patients with LVEF ≥50%, those with LVEF <30% had less improvement in SAQ Summary Score (-5.2 points; 95% confidence interval: -9.0 to -1.5; p = 0.01) and Rose Dyspnea Scale (+0.5 points; 95% confidence interval: 0.1 to 0.8; p = 0.01), with no difference in odds of angina (odds ratio: 1.3; 95% confidence interval: 0.6 to 3.0; p = 0.48). Health status improvement was similar between patients with LVEF ≥50% and LVEF 30% to 49%.

Conclusions: Although health status improvement was less in patients with severely reduced LVEF compared with those with normal LVEF, each group experienced large health status improvements after CTO-PCI.
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http://dx.doi.org/10.1016/j.jcin.2018.07.058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511279PMC
November 2018

Right ventricular afterload predicts long-term transition from parenteral to oral treprostinil in pulmonary arterial hypertension.

Pulm Circ 2018 Oct-Dec;8(4):2045894018797270. Epub 2018 Aug 20.

2 Division of Pulmonary, Critical Care, Sleep, and Allergy Medicine, University of Arizona, Tucson, AZ, USA.

Despite the increasing trends, reports on long-term follow-up are limited on transitioning from parenteral to oral treprostinil therapy in patients with pulmonary arterial hypertension (PAH). We investigated both the effectiveness of parenteral to oral treprostinil transition and the characteristics associated with transition failure over a duration of two years. The study included 37 Group I functional class I and II patients with PAH on combination therapy. Patients were excluded if cardiac index ≤2.2 L/min/m, right atrial pressure ≥11 mmHg, or 6-min walk distance ≤250 m. Patients were categorized as successful (Transition) or unsuccessful (Transition) transition based on clinical stability, or a parenteral comparator (Parenteral) if they remained on parenteral therapy (no transition). All patients underwent two right heart catheterizations, one at enrollment and a second post transition. Of 24 total transition patients, 46% were classified as Transition. Transition occurred on average 577 days post transition. Both Transition and Transition had similar hemodynamics at diagnosis and treprostinil dose before and after transition. Before transition, the pulmonary vascular resistance (PVR) was significantly higher in the Transition (6.7 ± 2 WU) vs. Transition group (3.5 ± 1.5 WU). At follow-up catheterization, the Transition group demonstrated further increases in PVR, greater than the Parenteral group, without recovery despite "rescue" therapy in the Transition group. A pre-transition PVR of 4.16 WU discriminated the Transition from the Transition group. While a subset of PAH patients on combination therapy may be safely transitioned from parenteral to oral treprostinil, caution should be exercised in patients with elevated baseline PVR to avoid irreversible destabilization.
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http://dx.doi.org/10.1177/2045894018797270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122247PMC
August 2018

Telemedicine in the Intensive Care Unit: Improved Access to Care at What Cost?

Crit Care Nurs Clin North Am 2018 Jun 21;30(2):289-296. Epub 2018 Mar 21.

University of Arizona College of Medicine, Sarver Heart Center, 1501 North Campbell Avenue, Room 5157-A, PO Box 245046, Tucson, AZ 85718, USA.

Health systems across the United States are adopting intensive care unit telemedicine programs to improve patient outcomes. Research demonstrates the potential for decreased mortality and length of stay for patients of these remotely monitored units. Financial models and studies point to cost-effectiveness and the possibility of cost savings in the face of abundant startup costs. Questions remain as to the true financial implications of these programs and targeted populations that may see the greatest benefit. Despite recent growth, widespread adoption may be limited until these unknowns are answered.
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http://dx.doi.org/10.1016/j.cnc.2018.02.010DOI Listing
June 2018

New Therapeutic Target in Heart Failure: Achieving and Maintaining Normokalemia.

Circulation 2018 03;137(13):1331-1333

Division of Cardiovascular Medicine, University of Arizona, Tucson.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.033854DOI Listing
March 2018

An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamide riboside (NR) and its effects on blood NAD+ levels in healthy volunteers.

PLoS One 2017 6;12(12):e0186459. Epub 2017 Dec 6.

Division of Cardiology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America.

Objectives: The co-primary objectives of this study were to determine the human pharmacokinetics (PK) of oral NR and the effect of NR on whole blood nicotinamide adenine dinucleotide (NAD+) levels.

Background: Though mitochondrial dysfunction plays a critical role in the development and progression of heart failure, no mitochondria-targeted therapies have been translated into clinical practice. Recent murine studies have reported associations between imbalances in the NADH/NAD+ ratio with mitochondrial dysfunction in multiple tissues, including myocardium. Moreover, an NAD+ precursor, nicotinamide mononucleotide, improved cardiac function, while another NAD+ precursor, nicotinamide riboside (NR), improved mitochondrial function in muscle, liver and brown adipose. Thus, PK studies of NR in humans is critical for future clinical trials.

Methods: In this non-randomized, open-label PK study of 8 healthy volunteers, 250 mg NR was orally administered on Days 1 and 2, then uptitrated to peak dose of 1000 mg twice daily on Days 7 and 8. On the morning of Day 9, subjects completed a 24-hour PK study after receiving 1000 mg NR at t = 0. Whole-blood levels of NR, clinical blood chemistry, and NAD+ levels were analyzed.

Results: Oral NR was well tolerated with no adverse events. Significant increases comparing baseline to mean concentrations at steady state (Cave,ss) were observed for both NR (p = 0.03) and NAD+ (p = 0.001); the latter increased by 100%. Absolute changes from baseline to Day 9 in NR and NAD+ levels correlated highly (R2 = 0.72, p = 0.008).

Conclusions: Because NR increases circulating NAD+ in humans, NR may have potential as a therapy in patients with mitochondrial dysfunction due to genetic and/or acquired diseases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186459PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5718430PMC
January 2018

Relative prosthesis-patient mismatch after transcatheter aortic valve replacement: The impact of morbid obesity.

Catheter Cardiovasc Interv 2017 Aug 27;90(2):341-345. Epub 2016 Aug 27.

Division of Cardiology of the University of Washington School of Medicine, Seattle, WA.

Prosthesis-patient mismatch (PPM) is defined as a small effective orifice area (EOA) of a normally functioning prosthetic valve in relation to patient body size. Even moderate impediment to forward flow has been associated with an increase in all-cause mortality. We report an unusual cause of PPM where a transcatheter implantation of a large EOA valve in an aortic position results in relative PPM in a patient with morbid obesity. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ccd.26721DOI Listing
August 2017

Ketones Step to the Plate: A Game Changer for Metabolic Remodeling in Heart Failure?

Circulation 2016 Feb 27;133(8):689-91. Epub 2016 Jan 27.

From Mitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine (S.C.K., R.T.) and Cardiology Division, Department of Medicine (S.A.), University of Washington, Seattle.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.116.021230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826559PMC
February 2016

A Diet Rich in Medium-Chain Fatty Acids Improves Systolic Function and Alters the Lipidomic Profile in Patients With Type 2 Diabetes: A Pilot Study.

J Clin Endocrinol Metab 2016 Feb 10;101(2):504-12. Epub 2015 Dec 10.

Department of Medicine (S.A.), Program in Physical Therapy (W.T.C., S.B.R.), Diabetic Cardiovascular Disease Center (H.J., D.S.O., J.E.S., M.F.), Mallinckrodt Institute of Radiology (A.R.C., R.O'C., A.B., C.J.-N.), Gastroenterology Division (K.K., C.A.S., S.W.), Lifestyle Intervention Research Core, Cardiology Division (A.D.W., V.G.D.-R., L.R.P.), Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.

Context: Excessive cardiac long-chain fatty acid (LCFA) metabolism/storage causes cardiomyopathy in animal models of type 2 diabetes. Medium-chain fatty acids (MCFAs) are absorbed and oxidized efficiently. Data in animal models of diabetes suggest MCFAs may benefit the heart.

Objective: Our objective was to test the effects of an MCFA-rich diet vs an LCFA-rich diet on plasma lipids, cardiac steatosis, and function in patients with type 2 diabetes.

Design: This was a double-blind, randomized, 2-week matched-feeding study.

Setting: The study included ambulatory patients in the general community.

Patients: Sixteen patients, ages 37-65 years, with type 2 diabetes, an ejection fraction greater than 45%, and no other systemic disease were included.

Intervention: Fourteen days of a diet rich in MCFAs or LCFAs, containing 38% as fat in total, was undertaken.

Main Outcome Measures: Cardiac steatosis and function were the main outcome measures, with lipidomic changes considered a secondary outcome.

Results: The relatively load-independent measure of cardiac contractility, S', improved in the MCFA group (P < .05). Weight-adjusted stroke volume and cardiac output decreased in the LCFA group (both P < .05). The MCFA, but not the LCFA, diet decreased several plasma sphingolipids, ceramide, and acylcarnitines implicated in diabetic cardiomyopathy, and changes in several sphingolipids correlated with improved fasting insulins.

Conclusions: Although a diet high in MCFAs does not change cardiac steatosis, our findings suggest that the MCFA-rich diet alters the plasma lipidome and may benefit or at least not harm cardiac function and fasting insulin levels in humans with type 2 diabetes. Larger, long-term studies are needed to further evaluate these effects in less-controlled settings.
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http://dx.doi.org/10.1210/jc.2015-3292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880128PMC
February 2016
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