68 results on '"David M. Systrom"'
Search Results
2. Impact of right ventricular work and pulmonary arterial compliance on peak exercise oxygen uptake in idiopathic pulmonary arterial hypertension
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Luiz Eduardo Nery, Rudolf K.F. Oliveira, Carolina M.S. Messina, Roberta Pulcheri Ramos, Eloara V.M. Ferreira, David M. Systrom, Jaquelina S. Ota-Arakaki, Angelo X.C. Fonseca, and Inderjit Singh
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Adult ,Male ,medicine.medical_specialty ,Cardiac output ,Hypertension, Pulmonary ,Ventricular Dysfunction, Right ,Cardiac index ,Pulmonary Artery ,030204 cardiovascular system & hematology ,Pulmonary compliance ,03 medical and health sciences ,0302 clinical medicine ,Afterload ,Internal medicine ,medicine ,Humans ,Familial Primary Pulmonary Hypertension ,030212 general & internal medicine ,Pulmonary wedge pressure ,business.industry ,Stroke volume ,medicine.disease ,Pulmonary hypertension ,Oxygen ,medicine.anatomical_structure ,Ventricular Function, Right ,Vascular resistance ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Pulmonary arterial hypertension (PAH) is associated with increased right ventricular (RV) afterload, RV dysfunction and decreased peak oxygen uptake (pVO2). However, the pulmonary hemodynamic mechanisms measured by exercise right heart catheterization (RHC) that contribute to reduced pVO2 in idiopathic PAH (IPAH) are not completely characterized. Therefore, we sought to evaluate the exercise RHC determinants of pVO2 in patients with IPAH. Methods 519 consecutive patients with suspected and/or confirmed pulmonary hypertension were prospectively screened to identify 20 patients with IPAH. All IPAH patients were prospectively evaluated with resting and exercise RHC and cardiopulmonary exercise testing. Results 85% of the patients were female; the median age was 34[29–42] years old. At peak exercise, mean pulmonary arterial (PA) pressure was 76 ± 17 mmHg, PA wedge pressure was 14 ± 5 mmHg, cardiac output (CO) was 5.7 ± 1.9 L/min, pulmonary vascular resistance was 959 ± 401 dynes/s/cm5 and PA compliance was 0.9[0.6–1.2] ml/mmHg. On univariate analysis, pVO2 positively correlated to peak CO, peak cardiac index, peak stroke volume index, peak RV stroke work index (RVSWI) and peak oxygen saturation. There was a negative correlation between pVO2 and Δ (rest to peak change) PA compliance. In age-adjusted multivariate model, peak RVSWI (Coefficient = 0.15, Beta = 0.63, 95% CI [0.07–0.22], p Conclusions In conclusion, a load dependent measurement of RV function (RVSWI) and the pulsatile component of RV afterload (ΔPA compliance) significantly influence pVO2 in IPAH, further highlighting the pivotal role of hemodynamic coupling to IPAH exercise capacity.
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- 2021
3. Neurovascular Dysregulation and Acute Exercise Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Placebo-Controlled Trial of Pyridostigmine
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Phillip, Joseph, Rosa, Pari, Sarah, Miller, Arabella, Warren, Mary Catherine, Stovall, Johanna, Squires, Chia-Jung, Chang, Wenzhong, Xiao, Aaron B, Waxman, and David M, Systrom
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Fatigue Syndrome, Chronic ,Exercise Test ,Humans ,Exercise ,Pyridostigmine Bromide - Abstract
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by intractable fatigue, postexertional malaise, and orthostatic intolerance, but its pathophysiology is poorly understood. Pharmacologic cholinergic stimulation was used to test the hypothesis that neurovascular dysregulation underlies exercise intolerance in ME/CFS.Does neurovascular dysregulation contribute to exercise intolerance in ME/CFS, and can its treatment improve exercise capacity?Forty-five subjects with ME/CFS were enrolled in a single-center, randomized, double-blind, placebo-controlled trial. Subjects were assigned in a 1:1 ratio to receive a 60-mg dose of oral pyridostigmine or placebo after an invasive cardiopulmonary exercise test (iCPET). A second iCPET was performed 50 min later. The primary end point was the difference in peak exercise oxygen uptake (VoTwenty-three subjects were assigned to receive pyridostigmine and 22 to receive placebo. The peak VoPyridostigmine improves peak VoClinicalTrials.gov; No.: NCT03674541; URL: www.gov.
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- 2022
4. Systemic vascular distensibility relates to exercise capacity in connective tissue disease
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Aaron B. Waxman, Mariana Faria-Urbina, Inderjit Singh, David M. Systrom, Rudolf K.F. Oliveira, Robert Naeije, and William M. Oldham
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Male ,medicine.medical_specialty ,Exercise intolerance ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Internal medicine ,medicine ,Humans ,Aerobic exercise ,Pharmacology (medical) ,Connective Tissue Diseases ,Cardiopulmonary disease ,030203 arthritis & rheumatology ,Exercise Tolerance ,business.industry ,Stroke volume ,Middle Aged ,medicine.disease ,Pulmonary hypertension ,Connective tissue disease ,Elasticity ,Oxygen ,Dyspnea ,Heart failure ,Microvessels ,Exercise Test ,Cardiology ,Female ,CTD ,medicine.symptom ,business - Abstract
Objective Exercise intolerance is a common clinical manifestation of CTD. Frequently, CTD patients have associated cardio-pulmonary disease, including pulmonary hypertension or heart failure that impairs aerobic exercise capacity (pVO2). The contribution of the systemic micro-vasculature to reduced exercise capacity in CTD patients without cardiopulmonary disease has not been fully described. In this study, we sought to examine the role of systemic vascular distensibility, α in reducing exercise capacity (i.e. pVO2) in CTD patients. Methods Systemic and pulmonary vascular distensibility, α (%/mmHg) was determined from multipoint systemic pressure-flow plots during invasive cardiopulmonary exercise testing with pulmonary and radial arterial catheters in place in 42 CTD patients without cardiopulmonary disease and compared with 24 age and gender matched normal controls. Results During exercise, systemic vascular distensibility, α was reduced in CTD patients compared with controls (0.20 ± 0.12%/mmHg vs 0.30 ± 0.13%/mmHg, P =0.01). The reduced systemic vascular distensibility α, was associated with impaired stroke volume augmentation. On multivariate analysis, systemic vascular distensibility, α was associated with a decreased exercise capacity (pVO2) and decreased systemic oxygen extraction. Conclusion Systemic vascular distensibility, α is associated with impaired systemic oxygen extraction and decreased aerobic capacity in patients with CTD without cardiopulmonary disease.
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- 2020
5. Pulmonary Vascular and Right Ventricular Burden During Exercise in Interstitial Lung Disease
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David M. Systrom, Paul Hoover, Aaron B. Waxman, Paul F. Dellaripa, and Rudolf K.F. Oliveira
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Adult ,Male ,Pulmonary and Respiratory Medicine ,Right heart catheterization ,medicine.medical_specialty ,Hypertension, Pulmonary ,Ventricular Dysfunction, Right ,Hemodynamics ,Critical Care and Intensive Care Medicine ,behavioral disciplines and activities ,03 medical and health sciences ,Oxygen Consumption ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Pulmonary wedge pressure ,Exercise ,Aged ,Exercise Tolerance ,business.industry ,Interstitial lung disease ,Middle Aged ,respiratory system ,medicine.disease ,Pulmonary hypertension ,Connective tissue disease ,respiratory tract diseases ,body regions ,Pulmonary and Cardiovascular: Original Research ,medicine.anatomical_structure ,030228 respiratory system ,Case-Control Studies ,Exercise Test ,Respiratory Mechanics ,Vascular resistance ,Cardiology ,Female ,Vascular Resistance ,Lung Diseases, Interstitial ,Cardiology and Cardiovascular Medicine ,business ,Anaerobic exercise - Abstract
BACKGROUND: Pulmonary hypertension (PH) adversely affects patient’s exercise capacity in interstitial lung disease (ILD). The impact of pulmonary vascular and right ventricular (RV) dysfunction, however, has traditionally been believed to be mild and clinically relevant principally in advanced lung disease states. RESEARCH QUESTION: The aim of this study was to evaluate the relative contributions of pulmonary mechanics, pulmonary vascular function, and RV function to the ILD exercise limit. STUDY DESIGN AND METHODS: Forty-nine patients with ILD who underwent resting right heart catheterization followed by invasive exercise testing were evaluated. Patients with PH at rest (ILD + rPH) and with PH diagnosed exclusively during exercise (ILD + ePH) were contrasted with ILD patients without PH (ILD non-PH). RESULTS: Peak oxygen consumption was reduced in ILD + rPH (61 ± 10% predicted) and ILD + ePH (67 ± 13% predicted) compared with ILD non-PH (81 ± 16% predicted; P < .001 and P = .016, respectively). Each ILD hemodynamic phenotype presented distinct patterns of dynamic changes of pulmonary vascular compliance relative to pulmonary vascular resistance from rest to peak exercise. Peak RV stroke work index was increased in ILD + ePH (24.7 ± 8.2 g/m(2) per beat) and ILD + rPH (30.9 ± 6.1 g/m(2) per beat) compared with ILD non-PH (18.3 ± 6.4 g/m(2) per beat; P = .020 and P = .014). Ventilatory reserve was reduced in ILD + rPH compared with the other groups at the anaerobic threshold, but it was similar between ILD + ePH and ILD non-PH at the anaerobic threshold (0.32 ± 0.13 vs 0.30 ± 0.11; P = .921) and at peak exercise (0.70 ± 0.17 vs 0.73 ± 0.24; P = .872). INTERPRETATION: ILD with resting and exercise PH is associated with increased exercise RV work, reduced pulmonary vascular reserve, and reduced peak oxygen consumption. The findings highlight the role of pulmonary vascular and RV burden to ILD exercise limit.
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- 2020
6. Noninvasive Scale Measurement of Stroke Volume and Cardiac Output Compared With the Direct Fick Method: A Feasibility Study
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Daniel Yazdi, Suriya Sridaran, Sarah Smith, Corey Centen, Sarin Patel, Evan Wilson, Leah Gillon, Sunil Kapur, Julie A. Tracy, Katherine Lewine, David M. Systrom, and Calum A. MacRae
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machine learning and artificial ,exercise testing ,digital health ,heart failure ,Stroke Volume ,intelligence ,hemodynamics ,RC666-701 ,Feasibility Studies ,Humans ,Diseases of the circulatory (Cardiovascular) system ,Cardiac Output ,Cardiology and Cardiovascular Medicine ,Monitoring, Physiologic - Abstract
Background Objective markers of cardiac function are limited in the outpatient setting and may be beneficial for monitoring patients with chronic cardiac conditions. We assess the accuracy of a scale, with the ability to capture ballistocardiography, electrocardiography, and impedance plethysmography signals from a patient’s feet while standing on the scale, in measuring stroke volume and cardiac output compared with the gold‐standard direct Fick method. Methods and Results Thirty‐two patients with unexplained dyspnea undergoing level 3 invasive cardiopulmonary exercise test at a tertiary medical center were included in the final analysis. We obtained scale and direct Fick measurements of stroke volume and cardiac output before and immediately after invasive cardiopulmonary exercise test. Stroke volume and cardiac output from a cardiac scale and the direct Fick method correlated with r =0.81 and r =0.85, respectively ( P Conclusions In a proof‐of‐concept study, this novel scale with cardiac monitoring abilities may allow for noninvasive, longitudinal measures of cardiac function. Using the widely accepted form factor of a bathroom scale, this method of monitoring can be easily integrated into a patient’s lifestyle.
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- 2021
7. Persistent Exertional Intolerance After COVID-19: Insights From Invasive Cardiopulmonary Exercise Testing
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Inderjit, Singh, Phillip, Joseph, Paul M, Heerdt, Marjorie, Cullinan, Denyse D, Lutchmansingh, Mridu, Gulati, Jennifer D, Possick, David M, Systrom, and Aaron B, Waxman
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Male ,SV, stroke volume ,post-COVID-19 syndrome ,CO, cardiac output ,iCPET ,PVR, pulmonary vascular resistance ,hemodynamics ,SVI, stroke volume index ,PaCO2, partial pressure of carbon dioxide in arterial blood ,Oxygen Consumption ,Post-Acute COVID-19 Syndrome ,Humans ,CI, cardiac index ,Original Research ,COVID-19, coronavirus 19 disease ,VO2, oxygen consumption ,Exercise Tolerance ,mPAP, mean pulmonary artery pressure ,PAWP, pulmonary artery wedge pressure ,SARS-CoV-2 ,long haulers ,COVID-19 ,Stroke Volume ,EO2, systemic oxygen extraction ,Middle Aged ,SARS-CoV-2, severe acute respiratory syndrome cornovirus-2 ,Respiratory Function Tests ,VD/VT, dead space ,TPR, total pulmonary resistance ,Connecticut ,VE/VCO2, ventilatory efficiency ,Massachusetts ,iCPET, invasive cardiopulmonary exercise testing ,PaO2, partial pressure of oxygen in arterial blood ,Exercise Test ,CaVO2, arterial-mixed venous oxygen content difference ,Female ,cardiopulmonary exercise test - Abstract
Background Some Coronavirus disease 2019 (COVID-19) patients who have recovered from their acute infection after experiencing only mild symptoms continue to exhibit persistent exertional limitation that is often unexplained by conventional investigative studies. Research question What is the patho-physiological mechanism of exercise intolerance that underlies the post-COVID-19 long haul syndrome following COVID-19 in patients without cardio-pulmonary disease? Study Design and Methods This study examined the systemic and pulmonary hemodynamics, ventilation, and gas exchange in 10 post-COVID-19 patients without cardio-pulmonary disease during invasive cardiopulmonary exercise testing (iCPET) and compared the results to 10 age- and sex matched controls. These data were then used to define potential reasons for exertional limitation in the post-COVID-19 cohort. Results Post-COVID-19 patients exhibited markedly reduced peak exercise aerobic capacity (VO2) compared to controls (70±11%predicted vs. 131±45%predicted; p0.05). Additionally, post-COVID-19 patients demonstrated greater ventilatory inefficiency (i.e., abnormal VE/VCO2 slope: 35±5 vs. 27±5, p=0.01) compared to controls without an increase in dead space ventilation. Interpretation Post-COVID-19 patients without cardiopulmonary disease demonstrate a marked reduction in peak VO2 from a peripheral rather than a central cardiac limit along with an exaggerated hyper-ventilatory response during exercise.
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- 2021
8. Unexplained exertional intolerance associated with impaired systemic oxygen extraction
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Mário Santos, Donna Felsenstein, David M. Systrom, Kathryn H. Melamed, Mariana Faria Urbina, Aaron B. Waxman, Alexander R. Opotowsky, and Rudolf K.F. Oliveira
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Adult ,Male ,medicine.medical_specialty ,Anaerobic Threshold ,Sports medicine ,Physiology ,03 medical and health sciences ,0302 clinical medicine ,Hypocapnia ,Heart Rate ,Physiology (medical) ,Internal medicine ,Left shift ,Hyperventilation ,Chronic fatigue syndrome ,Humans ,Medicine ,Orthopedics and Sports Medicine ,Exercise ,Aged ,Cardiopulmonary disease ,Exercise Tolerance ,Pulmonary Gas Exchange ,business.industry ,Public Health, Environmental and Occupational Health ,Oxygen–haemoglobin dissociation curve ,030229 sport sciences ,General Medicine ,Middle Aged ,medicine.disease ,Cardiorespiratory Fitness ,Cardiology ,Arterial blood ,Female ,medicine.symptom ,Pulmonary Ventilation ,business ,030217 neurology & neurosurgery - Abstract
The clinical investigation of exertional intolerance generally focuses on cardiopulmonary diseases, while peripheral factors are often overlooked. We hypothesize that a subset of patients exists whose predominant exercise limitation is due to abnormal systemic oxygen extraction (SOE). We reviewed invasive cardiopulmonary exercise test (iCPET) results of 313 consecutive patients presenting with unexplained exertional intolerance. An exercise limit due to poor SOE was defined as peak exercise (Ca-vO2)/[Hb] ≤ 0.8 and VO2max 0.8, VO2max ≥ 80%, and no cardiac or pulmonary limit were considered otherwise normal. The otherwise normal group was divided into hyperventilators (HV) and normals (NL). Hyperventilation was defined as peak PaCO2
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- 2019
9. Perfusion Imaging Distinguishes Exercise Pulmonary Arterial Hypertension at Rest
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R. Scott Harris, Josanna Rodriguez-Lopez, David M. Systrom, Kathryn A. Hibbert, Vanessa J. Kelly, Puja Kohli, Aaron B. Waxman, Tilo Winkler, Richard N. Channick, Mamary Kone, Jose G. Venegas, and Ekaterina G Kehl
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Adult ,Male ,Pulmonary and Respiratory Medicine ,Pulmonary Arterial Hypertension ,medicine.medical_specialty ,business.industry ,Perfusion Imaging ,MEDLINE ,Perfusion scanning ,Middle Aged ,Critical Care and Intensive Care Medicine ,Young Adult ,Text mining ,Positron-Emission Tomography ,Internal medicine ,Correspondence ,medicine ,Cardiology ,Humans ,Female ,Exercise physiology ,Young adult ,business ,Exercise ,Rest (music) - Published
- 2019
10. Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1
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Jonas Axelsson, Robert S. Sheldon, Julian M. Stewart, Brent P. Goodman, Amanda J. Miller, Glen A. Cook, Steven Vernino, Tae H. Chung, Taylor A. Doherty, Jeffrey R. Boris, Cyndya A. Shibao, Melissa M. Cortez, Peter C. Rowe, Italo Biaggioni, Amy C. Arnold, Satish R. Raj, David M. Systrom, Hasan I. Abdallah, Mitchell G. Miglis, Blair P. Grubb, Kamal R. Chémali, David S. Goldstein, Artur Fedorowski, Jeffrey P. Moak, Kate M. Bourne, Lauren E. Stiles, Roy Freeman, Anil Darbari, Laura A. Pace, and André Diedrich
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medicine.medical_specialty ,Consensus ,Adolescent ,Orthostatic intolerance ,Exercise intolerance ,Article ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Postural Orthostatic Tachycardia Syndrome ,0302 clinical medicine ,Heart Rate ,Medicine ,Humans ,Clinical care ,Intensive care medicine ,Endocrine and Autonomic Systems ,business.industry ,Stressor ,technology, industry, and agriculture ,Expert consensus ,food and beverages ,medicine.disease ,United States ,Distress ,National Institutes of Health (U.S.) ,Orthostatic Intolerance ,Female ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Patient education - Abstract
Postural orthostatic tachycardia syndrome (POTS) is a chronic and often disabling disorder characterized by orthostatic intolerance with excessive heart rate increase without hypotension during upright posture. Patients often experience a constellation of other typical symptoms including fatigue, exercise intolerance and gastrointestinal distress. A typical patient with POTS is a female of child-bearing age, who often first displays symptoms in adolescence. The onset of POTS may be precipitated by immunological stressors such as a viral infection. A variety of pathophysiologies are involved in the abnormal postural tachycardia response; however, the pathophysiology of the syndrome is incompletely understood and undoubtedly multifaceted. Clinicians and researchers focused on POTS convened at the National Institutes of Health in July 2019 to discuss the current state of understanding of the pathophysiology of POTS and to identify priorities for POTS research. This article, the first of two articles summarizing the information discussed at this meeting, summarizes the current understanding of this disorder and best practices for clinical care. The evaluation of a patient with suspected POTS should seek to establish the diagnosis, identify co-morbid conditions, and exclude conditions that could cause or mimic the syndrome. Once diagnosed, management typically begins with patient education and non-pharmacologic treatment options. Various medications are often used to address specific symptoms, but there are currently no FDA-approved medications for the treatment of POTS, and evidence for many of the medications used to treat POTS is not robust.
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- 2021
11. Sex-Related Differences in Dynamic Right Ventricular-Pulmonary Vascular Coupling in Heart Failure With Preserved Ejection Fraction
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Rudolf K.F. Oliveira, Inderjit Singh, Rosa Pari, David M. Systrom, Paul M. Heerdt, and Aaron B. Waxman
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Pulmonary and Respiratory Medicine ,Male ,medicine.medical_specialty ,Cardiac Catheterization ,Systole ,Heart Ventricles ,Pulmonary Artery ,Critical Care and Intensive Care Medicine ,Incremental exercise ,03 medical and health sciences ,0302 clinical medicine ,Sex Factors ,Afterload ,Internal medicine ,medicine ,Ventricular Pressure ,Humans ,030212 general & internal medicine ,Pulmonary Wedge Pressure ,Sex Distribution ,Pulmonary wedge pressure ,Aged ,Retrospective Studies ,Heart Failure ,Exercise Tolerance ,business.industry ,Incidence ,Sex related ,Stroke Volume ,Stroke volume ,medicine.disease ,Pulmonary hypertension ,United States ,030228 respiratory system ,Echocardiography ,Cardiology ,Arterial elastance ,Ventricular Function, Right ,Female ,Vascular Resistance ,Cardiology and Cardiovascular Medicine ,business ,Heart failure with preserved ejection fraction ,Follow-Up Studies - Abstract
Background Right ventricular (RV) dysfunction is associated with poorer outcomes in heart failure with preserved ejection fraction (HFpEF). Although female subjects are more likely to have HFpEF, male subjects have worse prognosis and resting RV function. The contribution of dynamic RV-pulmonary arterial (RV-PA) coupling between sex and its impact on peak exercise capacity (VO2) in HFpEF is not known. Research Question The goal of this study was to investigate the differential effects of sex on RV-PA coupling during maximum incremental exercise in patients with HFpEF. Study Design and Methods This study examined rest and exercise invasive pulmonary hemodynamics in 22 male patients with HFpEF and 27 female patients with HFpEF. To further investigate the discrepancy in RV-PA response between sex, 26 age-matched control subjects (11 male subjects and 15 female subjects) were included. Single beat analysis of RV pressure waveforms was used to determine the end-systolic elastance (Ees) and pulmonary arterial elastance. RV-PA coupling was determined as the ratio of end-systolic elastance/PA elastance. Results Both HFpEF groups experienced decreased peak VO2 (% predicted). However, male patients with HFpEF experienced a greater decrement in peak VO2 compared with female patients (58 ± 16% vs 70 ± 15%; P Interpretation Male patients with HFpEF were more compromised regarding dynamic RV-PA uncoupling and reduced peak VO2 compared with female patients. This finding was driven by both RV contractile impairment and afterload mismatch. In contrast, female patients with HFpEF had preserved RV-PA coupling during exercise and better peak exercise VO2 compared with male patients with HFpEF.
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- 2020
12. Comprehensive Diagnostic Evaluation of Cardiovascular Physiology in Patients With Pulmonary Vascular Disease
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Erika B. Rosenzweig, Anna R. Hemnes, Rebecca Vanderpool, Miriam Jacob, Jennifer Wilcox, Evelyn M. Horn, Jane A. Leopold, Paul M. Hassoun, Robert P. Frantz, Franz Rischard, Aaron B. Waxman, Ryan J. Tedford, David M. Systrom, W.H. Wilson Tang, Harsimran Singh, Lei Xiao, Nicholas S. Hill, and Barry A. Borlaug
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Right heart catheterization ,Cardiac Catheterization ,medicine.medical_specialty ,Hypertension, Pulmonary ,Vasodilator Agents ,MEDLINE ,Hemodynamics ,Pulmonary Artery ,030204 cardiovascular system & hematology ,Diagnostic evaluation ,Article ,Patient Positioning ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,Internal medicine ,medicine ,Humans ,In patient ,Phenomics ,Pulmonary Gas Exchange ,Vascular disease ,business.industry ,medicine.disease ,Pulmonary hypertension ,Cardiovascular physiology ,030228 respiratory system ,Exercise Test ,Cardiology ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background: Invasive hemodynamic evaluation through right heart catheterization plays an essential role in the diagnosis, categorization, and risk stratification of patients with pulmonary hypertension. Methods: Subjects enrolled in the PVDOMICS (Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics) program undergo an extensive invasive hemodynamic evaluation that includes repeated measurements at rest and during several provocative physiological challenges. It is a National Institutes of Health/National Heart, Lung, and Blood Institute initiative to reclassify pulmonary hypertension groups based on clustered phenotypic and phenomic characteristics. At a subset of centers, participants also undergo an invasive cardiopulmonary exercise test to assess changes in hemodynamics and gas exchange during exercise. Conclusions: When coupled with other physiological testing and blood -omic analyses involved in the PVDOMICS study, the comprehensive right heart catheterization protocol described here holds promise to clarify the diagnosis and clustering of pulmonary hypertension patients into cohorts beyond the traditional 5 World Symposium on Pulmonary Hypertension groups. This article will describe the methods applied for invasive hemodynamic characterization in the PVDOMICS program. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02980887.
- Published
- 2020
13. Right ventriculo–arterial uncoupling and impaired contractile reserve in obese patients with unexplained exercise intolerance
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Richard G. Axell, David M. Systrom, Mariana Faria-Urbina, Andrew N. Priest, Aaron B. Waxman, Farbod N. Rahaghi, Colm McCabe, Rudolf K.F. Oliveira, and Luke Howard
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Male ,Pulmonary Circulation ,Cardiac output ,Physiology ,Hemodynamics ,030204 cardiovascular system & hematology ,ACTIVATION ,CARBON-DIOXIDE ,Coupling ,0302 clinical medicine ,CARDIAC-PERFORMANCE ,Ventricular Function ,Orthopedics and Sports Medicine ,HYPOXIC PULMONARY VASOCONSTRICTION ,1106 Human Movement And Sports Science ,Exercise Tolerance ,HYPERCAPNIA ,Central venous pressure ,VASCULAR-DISEASE ,General Medicine ,Middle Aged ,Atrial Function ,medicine.anatomical_structure ,PRESERVED EJECTION FRACTION ,Cardiology ,HEART-FAILURE ,Right ventricle ,Female ,Original Article ,medicine.symptom ,Life Sciences & Biomedicine ,medicine.medical_specialty ,Hypertension, Pulmonary ,Afterload ,Exercise intolerance ,03 medical and health sciences ,Coronary Circulation ,Physiology (medical) ,Internal medicine ,medicine.artery ,medicine ,Humans ,Obesity ,Exercise ,Aged ,Science & Technology ,HYPERTENSION ,business.industry ,Public Health, Environmental and Occupational Health ,Myocardial Contraction ,030228 respiratory system ,Pulmonary artery ,Vascular resistance ,Heart failure with preserved ejection fraction ,business ,Sport Sciences ,RESISTANCE - Abstract
Background Right ventricular (RV) dysfunction and heart failure with preserved ejection fraction may contribute to exercise intolerance in obesity. To further define RV exercise responses, we investigated RV–arterial coupling in obesity with and without development of exercise pulmonary venous hypertension (ePVH). Methods RV–arterial coupling defined as RV end-systolic elastance/pulmonary artery elastance (Ees/Ea) was calculated from invasive cardiopulmonary exercise test data in 6 controls, 8 obese patients without ePVH (Obese−ePVH) and 8 obese patients with ePVH (Obese+ePVH) within a larger series. ePVH was defined as a resting pulmonary arterial wedge pressure
- Published
- 2018
14. Network Analysis to Risk Stratify Patients With Exercise Intolerance
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Gaurav Choudhary, Horst Olschewski, Bradley M. Wertheim, Rudolf K.F. Oliveira, Jon Hainer, Aaron B. Waxman, Alexander R. Opotowsky, David M. Systrom, George A. Alba, Calum A. MacRae, Rui-Sheng Wang, Joseph Loscalzo, Gabor Kovacs, Jane A. Leopold, Bradley A. Maron, William M. Oldham, David M. Rubins, and Adrienn Tornyos
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Male ,medicine.medical_specialty ,Physiology ,Exercise intolerance ,030204 cardiovascular system & hematology ,Single Center ,Correlation ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,In patient ,Aged ,Cardiopulmonary disease ,Exercise Tolerance ,business.industry ,Clinical events ,Middle Aged ,medicine.disease ,Pulmonary hypertension ,Hospitalization ,030228 respiratory system ,Cardiovascular Diseases ,Exercise Test ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Network analysis - Abstract
Rationale: Current methods assessing clinical risk because of exercise intolerance in patients with cardiopulmonary disease rely on a small subset of traditional variables. Alternative strategies incorporating the spectrum of factors underlying prognosis in at-risk patients may be useful clinically, but are lacking. Objective: Use unbiased analyses to identify variables that correspond to clinical risk in patients with exercise intolerance. Methods and Results: Data from 738 consecutive patients referred for invasive cardiopulmonary exercise testing at a single center (2011–2015) were analyzed retrospectively (derivation cohort). A correlation network of invasive cardiopulmonary exercise testing parameters was assembled using |r|>0.5. From an exercise network of 39 variables (ie, nodes) and 98 correlations (ie, edges) corresponding to P −46 for each correlation, we focused on a subnetwork containing peak volume of oxygen consumption (pV o 2 ) and 9 linked nodes. K-mean clustering based on these 10 variables identified 4 novel patient clusters characterized by significant differences in 44 of 45 exercise measurements ( P o 2 and pV o 2 itself, the network model was less redundant and identified clusters that were more distinct. Cluster assignment from the network model was predictive of subsequent clinical events. For example, a 4.3-fold ( P P =0.0018; 95% CI, 1.5–5.2) increase in hazard for age- and pV o 2 -adjusted all-cause 3-year hospitalization, respectively, were observed between the highest versus lowest risk clusters. Using these data, we developed the first risk-stratification calculator for patients with exercise intolerance. When applying the risk calculator to patients in 2 independent invasive cardiopulmonary exercise testing cohorts (Boston and Graz, Austria), we observed a clinical risk profile that paralleled the derivation cohort. Conclusions: Network analyses were used to identify novel exercise groups and develop a point-of-care risk calculator. These data expand the range of useful clinical variables beyond pV o 2 that predict hospitalization in patients with exercise intolerance.
- Published
- 2018
15. Postural orthostatic tachycardia syndrome (POTS): Priorities for POTS care and research from a 2019 National Institutes of Health Expert Consensus Meeting - Part 2
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Mitchell G. Miglis, Hasan I. Abdallah, Kate M. Bourne, Lauren E. Stiles, Glen A. Cook, Roy Freeman, Jonas Axelsson, Peter C. Rowe, Italo Biaggioni, Robert S. Sheldon, Cyndya A. Shibao, David M. Systrom, Julian M. Stewart, Artur Fedorowski, Laura A. Pace, Blair P. Grubb, Anil Darbari, Taylor A. Doherty, Jeffrey P. Moak, Steven Vernino, Tae H. Chung, Amy C. Arnold, Satish R. Raj, Kamal R. Chémali, Brent P. Goodman, Melissa M. Cortez, Amanda J. Miller, Jeffrey R. Boris, David S. Goldstein, and André Diedrich
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medicine.medical_specialty ,Consensus ,Orthostatic intolerance ,Physician education ,Autonomic Nervous System ,Pathophysiology ,Article ,Cellular and Molecular Neuroscience ,Postural Orthostatic Tachycardia Syndrome ,Multidisciplinary approach ,Expert Consensus ,medicine ,Humans ,Intensive care medicine ,Workshop ,Endocrine and Autonomic Systems ,business.industry ,Expert consensus ,medicine.disease ,Chronic disorders ,United States ,Treatment ,Clinical research ,National Institutes of Health (U.S.) ,Orthostatic Intolerance ,Neurology (clinical) ,Orthostatic tachycardia ,business - Abstract
The National Institutes of Health hosted a workshop in 2019 to build consensus around the current state of understanding of the pathophysiology of postural orthostatic tachycardia syndrome (POTS) and to identify knowledge gaps that must be addressed to enhance clinical care of POTS patients through research. This second (of two) articles summarizes current knowledge gaps, and outlines the clinical and research priorities for POTS. POTS is a complex, multi-system, chronic disorder of the autonomic nervous system characterized by orthostatic intolerance and orthostatic tachycardia without hypotension. Patients often experience a host of other related disabling symptoms. The functional and economic impacts of this disorder are significant. The pathophysiology remains incompletely understood. Beyond the significant gaps in understanding the disorder itself, there is a paucity of evidence to guide treatment which can contribute to suboptimal care for this patient population. The vast majority of physicians have minimal to no familiarity or training in the assessment and management of POTS. Funding for POTS research remains very low relative to the size of the patient population and impact of the syndrome. In addition to efforts to improve awareness and physician education, an investment in research infrastructure including the development of standardized disease-specific evaluation tools and outcome measures is needed to facilitate effective collaborative research. A national POTS research consortium could facilitate well-controlled multidisciplinary clinical research studies and therapeutic trials. These priorities will require a substantial increase in the number of research investigators and the amount of research funding in this area.
- Published
- 2021
16. Left ventricular deformation at rest predicts exercise‐induced elevation in pulmonary artery wedge pressure in patients with unexplained dyspnoea
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Alexander R. Opotowsky, Aaron B. Waxman, Jose Rivero, Tor Biering-Sørensen, Amil M. Shah, Erin West, David M. Systrom, Shane D. McCullough, and Mário Santos
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Adult ,Male ,Cardiac Catheterization ,medicine.medical_specialty ,Systole ,Heart Ventricles ,Rest ,medicine.medical_treatment ,Diastole ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Pulmonary Wedge Pressure ,030212 general & internal medicine ,Pulmonary wedge pressure ,Exercise ,Aged ,Cardiac catheterization ,Heart Failure ,Ejection fraction ,business.industry ,Stroke Volume ,Stroke volume ,Middle Aged ,medicine.disease ,Dyspnea ,Echocardiography ,Heart failure ,Exercise Test ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,Heart failure with preserved ejection fraction - Abstract
Aims Impaired left ventricular (LV) deformation despite preserved LV ejection fraction (LVEF) is common and predicts outcomes in heart failure with preserved LVEF. We hypothesized that impaired LV deformation at rest is a marker of impaired cardiac systolic and diastolic reserve, and aimed to determine whether resting longitudinal (LS) and circumferential strain (CS) are associated with invasively measured haemodynamic response to exercise in patients with dyspnoea and a normal LVEF. Methods and results We studied 85 patients with LVEF ≥50% and free of significant valvular disease who were referred for evaluation of dyspnoea. All patients underwent rest echocardiography followed by right heart catheterization and cardiopulmonary exercise testing with concomitant invasive haemodynamic monitoring. The LS, CS and CS/LS ratio were measured by two-dimensional speckle-tracking echocardiography at rest. Lower absolute LS at rest was associated with greater increase in pulmonary arterial wedge pressure (PAWP) from rest to peak exercise (r = 0.23, P = 0.034). In contrast, higher absolute CS at rest predicted a greater increase in PAWP (r = - 0.27, P = 0.032) and greater stroke volume augmentation with exercise (r = - 0.26, P = 0.021). Higher CS/LS ratio was most predictive of elevation in PAWP with exercise (r = 0.30, P = 0.015). Of the measures of LV systolic and diastolic function assessed, the CS/LS ratio resulted in the highest area under the curve and specificity for the presence of rest- or exercise-induced pulmonary venous hypertension. Conclusion Left ventricular deformation at rest predicts exercise-induced rise in PAWP among patients with dyspnoea and a preserved LVEF. A pattern of rest deformation characterized by worse LS and exaggerated CS is most strongly associated with exercise-induced rise in PAWP.
- Published
- 2016
17. Fatigue, Sleep, and Autoimmune and Related Disorders
- Author
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Mark R. Zielinski, David M. Systrom, and Noel R. Rose
- Subjects
0301 basic medicine ,lcsh:Immunologic diseases. Allergy ,Central nervous system ,Immunology ,Disease ,Review ,Bioinformatics ,Autoimmune Diseases ,03 medical and health sciences ,0302 clinical medicine ,inflammasome ,medicine ,Chronic fatigue syndrome ,Immunology and Allergy ,Humans ,sleep ,neurovascular unit ,Autoimmune disease ,Inflammation ,Type 1 diabetes ,business.industry ,Multiple sclerosis ,Vagus Nerve ,autoimmune ,medicine.disease ,cytokines ,Circadian Rhythm ,030104 developmental biology ,Mood ,medicine.anatomical_structure ,Rheumatoid arthritis ,fatigue ,business ,lcsh:RC581-607 ,Reactive Oxygen Species ,Stress, Psychological ,030215 immunology - Abstract
Profound and debilitating fatigue is the most common complaint reported among individuals with autoimmune disease, such as systemic lupus erythematosus, multiple sclerosis, type 1 diabetes, celiac disease, chronic fatigue syndrome, and rheumatoid arthritis. Fatigue is multi-faceted and broadly defined, which makes understanding the cause of its manifestations especially difficult in conditions with diverse pathology including autoimmune diseases. In general, fatigue is defined by debilitating periods of exhaustion that interfere with normal activities. The severity and duration of fatigue episodes vary, but fatigue can cause difficulty for even simple tasks like climbing stairs or crossing the room. The exact mechanisms of fatigue are not well understood, perhaps due to its broad definition. Nevertheless, physiological processes known to play a role in fatigue include oxygen/nutrient supply, metabolism, mood, motivation, and sleepiness—all which are affected by inflammation. Additionally, an important contributing element to fatigue is the central nervous system—a region impacted either directly or indirectly in numerous autoimmune and related disorders. This review describes how inflammation and the central nervous system contribute to fatigue and suggests potential mechanisms involved in fatigue that are likely exhibited in autoimmune and related diseases.
- Published
- 2019
18. Pulmonary Vascular Distensibility and Early Pulmonary Vascular Remodeling in Pulmonary Hypertension
- Author
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William M. Oldham, David M. Systrom, Robert Naeije, Rudolf R.K.F. Oliveira, Aaron B. Waxman, Farbod N. Rahaghi, and Inderjit Singh
- Subjects
Pulmonary and Respiratory Medicine ,Adult ,Male ,medicine.medical_specialty ,Cardiac output ,Hypertension, Pulmonary ,Ventricular Dysfunction, Right ,Pulmonary Artery ,Vascular Remodeling ,Critical Care and Intensive Care Medicine ,Vascular remodelling in the embryo ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine.artery ,medicine ,Aerobic exercise ,Humans ,030212 general & internal medicine ,Pulmonary wedge pressure ,Aged ,Retrospective Studies ,Aged, 80 and over ,Heart Failure ,Exercise Tolerance ,business.industry ,Stroke Volume ,medicine.disease ,Pulmonary hypertension ,medicine.anatomical_structure ,030228 respiratory system ,Heart failure ,Pulmonary artery ,Vascular resistance ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,Heart failure with preserved ejection fraction ,business - Abstract
Background Exercise stress testing of the pulmonary circulation may uncover decreased pulmonary vascular (PV) distensibility as a cause of impaired aerobic exercise capacity and right ventricular (RV)-pulmonary arterial (PA) uncoupling. As such, it may help in the differential diagnosis of unexplained dyspnea, including pulmonary hypertension (PH) and/or heart failure with preserved ejection fraction (HFpEF). We investigated rest and exercise invasive pulmonary hemodynamics, ventilation, and gas exchange in patients with unexplained dyspnea, including 44 patients with HFpEF (of whom 20 had a normal pulmonary vascular resistance [PVR] during exercise [ie, passive HFpEF] and 24 had a higher than normal exercise PVR), 22 patients with exercise PH, 19 patients with pulmonary arterial hypertension (PAH), and 24 age- and sex-matched normal control subjects. Methods A PV distensibility coefficient α (%/mm Hg) was determined from multipoint PV pressure-flow plots. RV-PA coupling was quantified from the analysis of RV pressure curves to determine ratios of end-systolic to arterial elastances (Ees/Ea). Aerobic exercise capacity was estimated by peak oxygen consumption. Results The α coefficient decreased from 1.35 ± 0.58%/mm Hg in control subjects and 1.1 ± 0.48%/mm Hg in patients with passive HFpEF to 0.62 ± 0.32%/mm Hg in exercise PH, 0.54 ± 0.27%/mm Hg in HFpEF with high exercise PVR, and 0.18 ± 0.16%/mm Hg in PAH. On multivariate analysis, PV distensibility was associated with decreased Ees/Ea and maximal volume of oxygen consumed. Conclusions PV distensibility is an early and sensitive hemodynamic marker of PV disease that is associated with RV-PA uncoupling and decreased aerobic exercise capacity.
- Published
- 2019
19. Right Ventricular-Arterial Uncoupling During Exercise in Heart Failure With Preserved Ejection Fraction: Role of Pulmonary Vascular Dysfunction
- Author
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Inderjit, Singh, Farbod N, Rahaghi, Robert, Naeije, Rudolf K F, Oliveira, David M, Systrom, and Aaron B, Waxman
- Subjects
Aged, 80 and over ,Heart Failure ,Male ,Pulmonary Circulation ,Exercise Tolerance ,Pulmonary Gas Exchange ,Ventricular Dysfunction, Right ,Stroke Volume ,Middle Aged ,Pulmonary Artery ,Oxygen Consumption ,Vascular Stiffness ,Exercise Test ,Humans ,Female ,Vascular Resistance ,Pulmonary Ventilation ,Exercise ,Aged - Abstract
Right ventricular (RV) dysfunction is associated with shortened life expectancy in heart failure with preserved ejection fraction (HFpEF). The contribution of pulmonary vascular dysfunction to RV dysfunction in HFpEF is not well understood.We investigated rest and exercise invasive pulmonary hemodynamics, ventilation, and gas exchange in 67 patients with HFpEF (of whom 28 had an abnormal pulmonary vascular response during exercise referred to as HFpEF+PVR group and 39 had a normal pulmonary vascular response during exercise referred to as HFpEF group) and in 21 matched control subjects.Both groups of patients with HFpEF had a markedly decreased peak oxygen consumption (VoWe conclude that RV-PA uncoupling is common in HFpEF and is caused by both intrinsic RV contractile impairment and afterload mismatch. Resting and dynamic RV-PA uncoupling in HFpEF is driven by an increase in RV pulsatile rather than resistive afterload. However, with the additive effects of increased RV resistive afterload, RV-PA uncoupling worsens dynamically during exercise.
- Published
- 2019
20. Dyspnea and an Arteriovenous Fistula
- Author
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David M. Systrom, Anna Moniodis, and Jonathan Ginns
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,business.industry ,0206 medical engineering ,MEDLINE ,Arteriovenous fistula ,02 engineering and technology ,030204 cardiovascular system & hematology ,medicine.disease ,020601 biomedical engineering ,Surgery ,03 medical and health sciences ,Dyspnea ,0302 clinical medicine ,Arteriovenous Fistula ,medicine ,Humans ,Female ,business ,Aged - Published
- 2016
21. Pulmonary haemodynamics and mortality in chronic hypersensitivity pneumonitis
- Author
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Carlos Alberto de Castro Pereira, Paula S. Gomes, Carolina M.S. Messina, Rudolf K.F. Oliveira, Eloara V.M. Ferreira, Roberta Pulcheri Ramos, David M. Systrom, Andrea Gimenez, and Jaquelina S. Ota-Arakaki
- Subjects
Pulmonary and Respiratory Medicine ,Adult ,Male ,medicine.medical_specialty ,MEDLINE ,Hemodynamics ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Aged ,business.industry ,Middle Aged ,medicine.disease ,Chronic disease ,030228 respiratory system ,ROC Curve ,Chronic Disease ,Pulmonary haemodynamics ,Female ,business ,Hypersensitivity pneumonitis ,Brazil ,Alveolitis, Extrinsic Allergic - Abstract
Indices of pulmonary vascular dysfunction are associated with mortality in chronic hypersensitivity pneumonitis http://ow.ly/1nwG30jwTSm
- Published
- 2017
22. E/e′ Ratio in Patients With Unexplained Dyspnea
- Author
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Amil M. Shah, Jose Rivero, Aaron B. Waxman, Shane D. McCullough, Mário Santos, Alexander R. Opotowsky, Erin West, and David M. Systrom
- Subjects
Adult ,Male ,Cardiac Catheterization ,medicine.medical_specialty ,Time Factors ,Supine position ,Hemodynamics ,Patient Positioning ,Ventricular Function, Left ,Article ,Predictive Value of Tests ,Risk Factors ,Internal medicine ,Supine Position ,Ventricular Pressure ,medicine ,Humans ,In patient ,Pulmonary Wedge Pressure ,Pulmonary wedge pressure ,Aged ,Ultrasonography ,business.industry ,Limits of agreement ,Reproducibility of Results ,Stroke Volume ,Middle Aged ,medicine.disease ,Surgery ,Dyspnea ,ROC Curve ,Area Under Curve ,Heart failure ,Cardiology ,Mitral Valve ,Female ,Cardiology and Cardiovascular Medicine ,Ventricular filling ,business ,Heart failure with preserved ejection fraction - Abstract
Background— Elevated left ventricular filling pressure is a cardinal feature of heart failure with preserved ejection fraction. Mitral E/e′ ratio has been proposed as a noninvasive measure of left ventricular filling pressure. We studied the accuracy of E/e′ to estimate and track changes of left ventricular filling pressure in patients with unexplained dyspnea. Methods and Results— We performed supine and upright transthoracic echocardiography in 118 patients with unexplained dyspnea who underwent right heart catheterization. Supine E/e′ ratio modestly but significantly correlated with supine pulmonary arterial wedge pressure (PAWP; r =0.36; P P P P P =0.57). Positional change in PAWP correlated modestly with change in E-wave ( r =0.37; P r =−0.04; P =0.77) and in half the patients the change in PAWP and E/e′ were directionally opposite. Conclusions— In patients with unexplained dyspnea, E/e′ ratio neither accurately estimates PAWP nor identifies patients with elevated PAWP consistent with heart failure with preserved ejection fraction. Positional changes in E/e′ ratio do not reflect changes in PAWP.
- Published
- 2015
23. Genetic and hypoxic alterations of the micro <scp>RNA</scp> ‐210‐ <scp>ISCU</scp> 1/2 axis promote iron–sulfur deficiency and pulmonary hypertension
- Author
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Mark A. Perrella, David J. Ross, Ivan O. Rosas, Rajesh Kumar, Brian B. Graham, Kevin P. White, Daniel G. Anderson, Sara O. Vargas, Rajeev Saggar, Omar F. Khan, Kevin J. Polach, Alexander R. Opotowsky, Rajan Saggar, Aaron B. Waxman, Kathleen J. Haley, Stephen Y. Chan, Majed Matar, James E. Dahlman, Bernadette R. Gochuico, Andrew Bader, Richard C Jin, Sofia Annis, David M. Systrom, W. Dean Wallace, Nicolai M. Johannessen, Robert Langer, Jay L. Zweier, B. Nelson Chau, Laurence A. Bindoff, Andrew E. Hale, Juan C. Osorio, Haydn M. Prosser, Craig Hemann, Yu Lu, Institute for Medical Engineering and Science, Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Chemical Engineering, Koch Institute for Integrative Cancer Research at MIT, Dahlman, James E., Bader, Andrew, Anderson, Daniel Griffith, and Langer, Robert
- Subjects
Iron-Sulfur Proteins ,Medisinske fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Generell patologi, patologisk anatomi : 719 [VDP] ,iron-sulfur ,030204 cardiovascular system & hematology ,Mitochondrion ,Cardiovascular ,Medical and Health Sciences ,Mice ,0302 clinical medicine ,Midical sciences: 700::Basic medical, dental and veterinary sciences: 710::Medical genetics: 714 [VDP] ,2.1 Biological and endogenous factors ,Hypoxia ,Lung ,0303 health sciences ,Gene knockdown ,Cultured ,microRNA ,Pulmonary ,Iron Deficiencies ,Biological Sciences ,3. Good health ,mitochondria ,medicine.anatomical_structure ,Biochemistry ,Hypertension ,Molecular Medicine ,Female ,medicine.symptom ,medicine.medical_specialty ,Endothelium ,Iron ,Cells ,Biology ,03 medical and health sciences ,Internal medicine ,endothelial ,Genetics ,medicine ,Animals ,Humans ,Genetic Predisposition to Disease ,Psychological repression ,iron–sulfur ,030304 developmental biology ,Endothelial Cells ,Metabolism ,Hypoxia (medical) ,medicine.disease ,Midical sciences: 700::Basic medical, dental and veterinary sciences: 710::General pathology, anatomical pathology: 719 [VDP] ,Pulmonary hypertension ,Medisinske fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk genetikk: 714 [VDP] ,MicroRNAs ,Endocrinology ,biology.protein ,ISCU ,metabolism ,Sulfur - Abstract
Iron–sulfur (Fe‐S) clusters are essential for mitochondrial metabolism, but their regulation in pulmonary hypertension (PH) remains enigmatic. We demonstrate that alterations of the miR‐210‐ISCU1/2 axis cause Fe‐S deficiencies in vivo and promote PH. In pulmonary vascular cells and particularly endothelium, hypoxic induction of miR‐210 and repression of the miR‐210 targets ISCU1/2 down‐regulated Fe‐S levels. In mouse and human vascular and endothelial tissue affected by PH, miR‐210 was elevated accompanied by decreased ISCU1/2 and Fe‐S integrity. In mice, miR‐210 repressed ISCU1/2 and promoted PH. Mice deficient in miR‐210, via genetic/pharmacologic means or via an endothelial‐specific manner, displayed increased ISCU1/2 and were resistant to Fe‐S‐dependent pathophenotypes and PH. Similar to hypoxia or miR‐210 overexpression, ISCU1/2 knockdown also promoted PH. Finally, cardiopulmonary exercise testing of a woman with homozygous ISCU mutations revealed exercise‐induced pulmonary vascular dysfunction. Thus, driven by acquired (hypoxia) or genetic causes, the miR‐210‐ISCU1/2 regulatory axis is a pathogenic lynchpin causing Fe‐S deficiency and PH. These findings carry broad translational implications for defining the metabolic origins of PH and potentially other metabolic diseases sharing similar underpinnings., National Institutes of Health (U.S.) (U54‐CA151884), National Institutes of Health (U.S.) (R01‐DE016516‐06), National Institutes of Health (U.S.) (EB000244)
- Published
- 2015
24. Exercise Oscillatory Ventilation in Patients With Fontan Physiology
- Author
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Alexander R. Opotowsky, Keri M. Shafer, Lilamarie Moko, Ana Ubeda Tikkanen, Fred M. Wu, David M. Systrom, Jonathan Rhodes, Gregory D. Lewis, Brittani Loukas, Ashwin S. Nathan, Michael J. Landzberg, and Rahul H. Rathod
- Subjects
Adult ,Heart Defects, Congenital ,Male ,medicine.medical_specialty ,Adolescent ,Heart Ventricles ,medicine.medical_treatment ,Fontan Procedure ,Cheyne–Stokes respiration ,Fontan procedure ,Young Adult ,Internal medicine ,medicine ,Humans ,Cheyne-Stokes Respiration ,Survival analysis ,Heart Failure ,business.industry ,Proportional hazards model ,medicine.disease ,Survival Analysis ,Surgery ,Cross-Sectional Studies ,medicine.anatomical_structure ,Ventricle ,Heart failure ,Exercise Test ,Breathing ,Cardiology ,Heart Transplantation ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Respiratory minute volume - Abstract
Background— Exercise oscillatory ventilation (EOV) refers to regular oscillations in minute ventilation (V E ) during exercise. Its presence correlates with heart failure severity and worse prognosis in adults with acquired heart failure. We evaluated the prevalence and predictive value of EOV in patients with single ventricle Fontan physiology. Methods and Results— We performed a cross-sectional analysis and prospective survival analysis of patients who had undergone a Fontan procedure and subsequent cardiopulmonary exercise test. Data were reviewed for baseline characteristics and incident mortality, heart transplant, or nonelective cardiovascular hospitalization. EOV was defined as regular oscillations for >60% of exercise duration with amplitude >15% of average V E . Survival analysis was performed using Cox regression. Among 253 subjects, EOV was present in 37.5%. Patients with EOV were younger (18.8±9.0 versus 21.7±10.1 years; P =0.02). EOV was associated with higher New York Heart Association functional class ( P =0.02) and V E /V CO 2 slope (36.8±6.9 versus 33.7±5.7; P =0.0002), but not with peak V O 2 (59.7±14.3 versus 61.0±16.0% predicted; P =0.52) or noninvasive measures of cardiac function. The presence of EOV was associated with slightly lower mean cardiac index but other invasive hemodynamic variables were similar. During a median follow-up of 5.5 years, 22 patients underwent transplant or died (n=19 primary deaths, 3 transplants with 2 subsequent deaths). EOV was associated with increased risk of death or transplant (hazard ratio, 3.9; 95% confidence interval, 1.5–10.0; P =0.002) and also predicted the combined outcome of death, transplant, or nonelective cardiovascular hospitalization after adjusting for New York Heart Association functional class, peak V O 2 , and other covariates (multivariable hazard ratio, 2.0; 95% confidence interval, 1.2–3.6; P =0.01). Conclusions— EOV is common in the Fontan population and strongly predicts lower transplant-free survival.
- Published
- 2015
25. PVDOMICS: A Multi-Center Study to Improve Understanding of Pulmonary Vascular Disease Through Phenomics
- Author
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Bo Hu, John H. Newman, David M. Systrom, Jason K. Lempel, Robert P. Frantz, Franz Rischard, Paul M. Hassoun, Jane A. Leopold, Erika B. Rosenzweig, Aiden Abidov, Jason X.-J. Yuan, Evelyn M. Horn, John Barnard, Lei Xiao, Serpil C. Erzurum, W.H. Wilson Tang, Wendy K. Chung, Suzy A. A. Comhair, Anna R. Hemnes, Aaron B. Waxman, Stephen C. Mathai, Michael P. Gray, Gerald J. Beck, Barry A. Borlaug, Nicholas S. Hill, Bradley A. Maron, Mitchell A. Olman, Micheala A. Aldred, and Gabriele Grunig
- Subjects
Lung Diseases ,medicine.medical_specialty ,Pathology ,Pulmonary Circulation ,Physiology ,Hypertension, Pulmonary ,Hemodynamics ,Disease ,030204 cardiovascular system & hematology ,Article ,03 medical and health sciences ,0302 clinical medicine ,medicine.artery ,medicine ,Humans ,Vascular Diseases ,Precision Medicine ,Intensive care medicine ,Lung ,Vascular disease ,business.industry ,Translational medicine ,medicine.disease ,Pulmonary hypertension ,United States ,medicine.anatomical_structure ,Blood pressure ,Phenotype ,030228 respiratory system ,Pulmonary artery ,Cardiology and Cardiovascular Medicine ,business ,National Heart, Lung, and Blood Institute (U.S.) - Abstract
The National Institutes of Health (NIH)/National Heart, Lung and Blood institute (NHLBI) launched an initiative, PVDOMICS (Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics) that aims to augment the current pulmonary hypertension (PH) classification based on shared biological features. PVDOMICS will enroll 1500 participants with PH and disease and healthy comparators. Enrollees will undergo deep clinical phenotyping, and blood will be acquired for comprehensive omic analyses that will focus on discovery of molecular-based subtypes of pulmonary vascular disease (PVD) through application of high dimensional model-based clustering methods. In addition to an updated, molecular classification of PVD, the phenomic data generated will be a rich resource to the broad community of heart and lung disease investigators. Editorial, see p 1106 PH is a hemodynamic condition that causes increased blood pressure in the pulmonary arteries and the right heart leading to adverse clinical outcomes. The current World Symposium on Pulmonary Hypertension (WSPH) classification of PH is based on a combination of patient characteristics, clinical features, and cardiopulmonary hemodynamics, and these features are used to inform treatment options.1 Aside from heritable pulmonary arterial hypertension, this classification is not tied to molecular or cellular pathobiologic mechanism to explain the pathogenesis of PH. The NIH has a vested interest in understanding the causes and natural history of PH, as well as the discovery of effective treatment options. Since the first large NIH registry of patients with pulmonary arterial hypertension >30 years ago,2 significant advances in scientific knowledge and translational medicine have occurred, highlighting a need for updating the current clinical classification system. The NHLBI has sponsored several workshops focusing on PVD research strategic planning over the past decade. PVD encompasses PH and PVD without PH, for example, pulmonary vasculitis and pathological pulmonary vascular remodeling without hemodynamic criteria for PH. Experts identified the need …
- Published
- 2017
26. Hemodynamic and metabolic characteristics associated with development of a right ventricular outflow tract pressure gradient during upright exercise
- Author
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Berto J. Bouma, David M. Systrom, Amil M. Shah, Barbara J.M. Mulder, Michael J. Landzberg, Bradley A. Maron, Alexander R. Opotowsky, Aaron B. Waxman, Annelieke C.M.J. van Riel, Rudolf K.F. Oliveira, Cardiology, Graduate School, APH - Personalized Medicine, APH - Aging & Later Life, Amsterdam Cardiovascular Sciences, ACS - Heart failure & arrhythmias, and ACS - Pulmonary hypertension & thrombosis
- Subjects
Male ,Cardiac Catheterization ,Supine position ,Cardiac index ,Hemodynamics ,lcsh:Medicine ,Blood Pressure ,030204 cardiovascular system & hematology ,Vascular Medicine ,0302 clinical medicine ,Heart Rate ,Medicine and Health Sciences ,Ventricular outflow tract ,Public and Occupational Health ,Pulmonary Arteries ,Cardiac Output ,lcsh:Science ,Multidisciplinary ,Central venous pressure ,Hematology ,Arteries ,Middle Aged ,Systolic Pressure ,Sports Science ,Echocardiography ,Cardiology ,Female ,Anatomy ,Research Article ,Adult ,medicine.medical_specialty ,Pulmonary Artery ,03 medical and health sciences ,Internal medicine ,Heart rate ,medicine ,Ventricular Pressure ,Humans ,Sports and Exercise Medicine ,Exercise ,Pressure gradient ,business.industry ,lcsh:R ,Biology and Life Sciences ,Physical Activity ,Blood pressure ,030228 respiratory system ,Physical Fitness ,Cardiovascular Anatomy ,Ventricular Function, Right ,Blood Vessels ,lcsh:Q ,business - Abstract
BACKGROUND We recently reported a novel observation that many patients with equal resting supine right ventricular(RV) and pulmonary artery(PA) systolic pressures develop an RV outflow tract(RVOT) pressure gradient during upright exercise. The current work details the characteristics of patients who develop such an RVOT gradient. METHODS We studied 294 patients (59.7±15.5 years-old, 49% male) referred for clinical invasive cardiopulmonary exercise testing, who did not have a resting RVOT pressure gradient defined by the simultaneously measured peak-to-peak difference between RV and PA systolic pressures. RESULTS The magnitude of RVOT gradient did not correspond to clinical or hemodynamic findings suggestive of right heart failure; rather, higher gradients were associated with favorable exercise findings. The presence of a high peak RVOT gradient (90th percentile, ≥33mmHg) was associated with male sex (70 vs. 46%, p = 0.01), younger age (43.6±17.7 vs. 61.8±13.9 years, p
- Published
- 2017
27. Invasive cardiopulmonary exercise testing in the evaluation of unexplained dyspnea: Insights from a multidisciplinary dyspnea center
- Author
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Rudolf R.K.F. Oliveira, Stephen C Resch, Barbara A. Cockrill, David M. Systrom, Wei Huang, and Aaron B. Waxman
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Epidemiology ,Hypertension, Pulmonary ,030204 cardiovascular system & hematology ,03 medical and health sciences ,Patient referral ,0302 clinical medicine ,Multidisciplinary approach ,Medicine ,Humans ,Intensive care medicine ,Aged ,Retrospective Studies ,Heart Failure ,Exercise Tolerance ,business.industry ,Diagnostic test ,Reproducibility of Results ,Cardiopulmonary exercise testing ,Middle Aged ,respiratory tract diseases ,Dyspnea ,030228 respiratory system ,Exercise Test ,Female ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
Background Unexplained dyspnea is a common diagnosis that often results in repeated diagnostic testing and even delayed treatments while a determination of the cause is being investigated. Through a retrospective study, we evaluated the diagnostic efficacy of a multidisciplinary dyspnea evaluation center (MDEC) using invasive cardiopulmonary exercise test to diagnose potential causes of unexplained dyspnea. Methods We reviewed the medical records of all patients referred with unexplained dyspnea to the MDEC between March 2011 and October 2014. We assessed the diagnostic efficacy before and after presentation to the MDEC. Results During the study period a total of 864 patients were referred to the MDEC and, of those, 530 patients underwent further investigation with invasive cardiopulmonary exercise test and constituted the study sample. The median age was 57 (44-68) years, 67.2% were women, and median body mass index was 26.22 (22.78-31.01). A diagnosis was made in 530 patients including: exercise pulmonary arterial hypertension of 88 (16.6%), heart failure with preserved ejection fraction of 94 (17.7%), dysautonomia 112 (21.1%), oxidative myopathy of 130 (24.5%), primary hyperventilation of 43 (8.1%), and other 58 (10.9%). The time from initial presentation to referral was significantly longer than time to diagnosis after referral for non-standardized conventional methods versus diagnosis through MDEC using invasive cardiopulmonary exercise test (511 days (292-1095 days) vs. 27 days (13-53 days), p 0.0001). In a subgroup analysis, we reviewed that patients referred from cardiovascular clinics were more likely to have a greater number of diagnostic tests performed and, conversely, patients referred from pulmonary clinics were more likely to have a greater number of treatments prescribed before referral to MDEC. Conclusions As a result of this retrospective study, we have evaluated that a multidisciplinary approach that includes invasive cardiopulmonary exercise test dramatically reduces the time to diagnosis compared with traditional treatment and testing methods.
- Published
- 2017
28. Pulmonary Vascular Resistance During Exercise Predicts Long-Term Outcomes in Heart Failure With Preserved Ejection Fraction
- Author
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Aaron B. Waxman, Rudolf K.F. Oliveira, Wei Huang, David M. Systrom, and Han Lei
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,030204 cardiovascular system & hematology ,Ventricular Function, Left ,03 medical and health sciences ,0302 clinical medicine ,Oxygen Consumption ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Pulmonary Wedge Pressure ,Pulmonary wedge pressure ,Survival rate ,Heart Failure ,Ejection fraction ,Exercise Tolerance ,business.industry ,Hazard ratio ,Stroke Volume ,Stroke volume ,Middle Aged ,medicine.disease ,Prognosis ,United States ,Survival Rate ,medicine.anatomical_structure ,Heart failure ,Vascular resistance ,Cardiology ,Exercise Test ,Female ,Vascular Resistance ,Cardiology and Cardiovascular Medicine ,business ,Heart failure with preserved ejection fraction ,Follow-Up Studies - Abstract
Background In heart failure with preserved ejection fraction (HFpEF), the prognostic value of pulmonary vascular dysfunction (PV-dysfunction), identified by elevated pulmonary vascular resistance (PVR) at peak exercise, is not completely understood. We evaluated the long-term prognostic implications of PV-dysfunction in HFpEF during exercise in consecutive patients undergoing invasive cardiopulmonary exercise testing for unexplained dyspnea. Methods Patients with HFpEF were classified into 2 main groups: resting HFpEF (n = 104, 62% female, age 61 years) with a pulmonary arterial wedge pressure (PAWP) >15 mmHg at rest; and exercise HFpEF (eHFpEF; n = 81) with a PAWP 20 mmHg during exercise. The eHFpEF group was further subdivided into eHFpEF + PV-dysfunction (peak PVR ≥80 dynes/s/cm −5 ; n = 55, 60% female, age 64) group and eHFpEF – PV-dysfunction (peak PVR −5 ; n = 26, 42% female, age 54 years) group. Outcomes were analyzed for the first 9 years of follow-up and included any cause mortality and heart failure (HF)-related hospitalizations. The mean follow-up time was 6.7 ± 2.6 years (0.5–9.0). Results Mortality rate did not differ among the groups. However, survival free of HF-related hospitalization was lower for the eHFpEF + PV-dysfunction group compared with eHFpEF – PV-dysfunction ( P = .01). These findings were similar between eHFpEF + PV-dysfunction and the resting HFpEF group ( P = .774). By Cox analysis, peak PVR ≥80 dynes/s/cm −5 was a predictor of HF-related hospitalization for eHFpEF (hazard ratio 5.73, 95% confidence interval 1.05–31.22, P = .01). In conclusion, the present study provides insight into the impact of PV-dysfunction on outcomes of patients with exercise-induced HFpEF. An elevated peak PVR is associated with a high risk of HF-related hospitalization.
- Published
- 2017
29. Accuracy of Echocardiography to Estimate Pulmonary Artery Pressures With Exercise
- Author
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Berto J. Bouma, Jose Rivero, Alexander R. Opotowsky, Annelieke C.M.J. van Riel, Aaron B. Waxman, David M. Systrom, Mário Santos, Amil M. Shah, Barbara J.M. Mulder, Michael J. Landzberg, Andy Dhimitri, Cardiology, APH - Personalized Medicine, APH - Aging & Later Life, Amsterdam Cardiovascular Sciences, ACS - Heart failure & arrhythmias, and ACS - Pulmonary hypertension & thrombosis
- Subjects
Male ,medicine.medical_specialty ,Haemodynamic response ,Hypertension, Pulmonary ,Regurgitation (circulation) ,Pulmonary Artery ,030204 cardiovascular system & hematology ,Patient Positioning ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,Predictive Value of Tests ,medicine.artery ,Internal medicine ,medicine ,Humans ,Arterial Pressure ,Radiology, Nuclear Medicine and imaging ,Aged ,Retrospective Studies ,Exercise Tolerance ,business.industry ,Area under the curve ,Reproducibility of Results ,Middle Aged ,medicine.disease ,Pulmonary hypertension ,Echocardiography, Doppler ,Tricuspid Valve Insufficiency ,Confidence interval ,Editorial ,Blood pressure ,ROC Curve ,030228 respiratory system ,Area Under Curve ,Catheterization, Swan-Ganz ,Pulmonary artery ,Exercise Test ,symbols ,Cardiology ,Female ,Tricuspid Valve ,Cardiology and Cardiovascular Medicine ,business ,Doppler effect ,Echocardiography, Stress - Abstract
Background— Exercise echocardiography is often applied as a noninvasive strategy to screen for abnormal pulmonary hemodynamic response, but it is technically challenging, and limited data exist regarding its accuracy to estimate pulmonary arterial pressure during exercise. Methods and Results— Among 65 patients with exertional intolerance undergoing upright invasive exercise testing, tricuspid regurgitation (TR) Doppler estimates and invasive measurement of pulmonary arterial pressure at rest and peak exercise were simultaneously obtained. TR Doppler envelopes were assessed for quality. Correlation, Bland–Altman, and receiver-operating characteristic curve analyses were performed to evaluate agreement and diagnostic accuracy. Mean age was 62±13 years, and 31% were male. High-quality (grade A) TR Doppler was present in 68% at rest and 34% at peak exercise. For grade A TR signals, echocardiographic measures of systolic pulmonary arterial pressure correlated reasonably well with invasive measurement at rest ( r =0.72, P r =0.75, P 3.0 mm Hg/L per minute increase), with 91% sensitivity and 82% specificity (area under the curve, 0.90; 95% confidence interval, 0.77–1.0; P =0.001). Conclusions— Agreement between echocardiographic and invasive measures of pulmonary pressures during upright exercise is good among the subset of patients with high-quality TR Doppler signal. While the limits of agreement are broad, our results suggest that in those patients, sensitivity is adequate to screen for abnormal pulmonary hemodynamic response during exercise.
- Published
- 2017
30. Abnormal spirometry after the Fontan procedure is common and associated with impaired aerobic capacity
- Author
-
Michael J. Landzberg, Dawn A. Ericson, Stephen M. Paridon, Alicia Casey, Jonathan Rhodes, Michael G. Earing, Fred M. Wu, John K. Triedman, Alexander R. Opotowsky, and David M. Systrom
- Subjects
Male ,Spirometry ,medicine.medical_specialty ,Adolescent ,Physiology ,medicine.medical_treatment ,Fontan Procedure ,Fontan procedure ,Pulmonary heart disease ,Integrative Cardiovascular Physiology and Pathophysiology ,Physiology (medical) ,Internal medicine ,Prevalence ,medicine ,Humans ,Exercise physiology ,Child ,Exercise ,Aerobic capacity ,Exercise Tolerance ,Lung ,medicine.diagnostic_test ,business.industry ,Exercise capacity ,Respiration Disorders ,medicine.disease ,United States ,Treatment Outcome ,medicine.anatomical_structure ,Exercise Test ,Physical therapy ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Impaired exercise capacity is common after the Fontan procedure and is attributed to cardiovascular limits. The Fontan circulation, however, is also distinctively vulnerable to unfavorable lung mechanics. This study aimed to define the prevalence and physiological relevance of pulmonary dysfunction in patients with Fontan physiology. We analyzed data from the Pediatric Heart Network Fontan Cross-Sectional Study to assess the prevalence and pattern of abnormal spirometry in Fontan patients (6–18 yr old) and investigated the relationship between low forced vital capacity (FVC) and maximum exercise variables, including peak O2consumption (V̇o2peak), among those who demonstrated adequate effort ( n = 260). Average ages at the time of exercise testing and Fontan completion were 13.2 ± 3.0 and 3.5 ± 2.2 yr old, respectively. Aerobic capacity was reduced (V̇o2peak: 67.3 ± 15.6% predicted). FVC averaged 79.0 ± 14.8% predicted, with 45.8% having a FVC less then the lower limit of normal. Only 7.8% demonstrated obstructive spirometry. Patients with low FVC had lower V̇o2peak(64.4 ± 15.9% vs. 69.7 ± 14.9% predicted, P < 0.01); low FVC independently predicted lower V̇o2peakafter adjusting for relevant covariates. Among those with V̇o2peak< 80% predicted ( n = 204/260), 22.5% demonstrated a pulmonary mechanical contribution to exercise limitation (breathing reserve < 20%). Those with both low FVC and ventilatory inefficiency (minute ventilation/CO2production > 40) had markedly reduced V̇o2peak(61.5 ± 15.3% vs. 72.0 ± 14.9% predicted, P < 0.01) and a higher prevalence of pulmonary mechanical limit compared with patients with normal FVC and efficient ventilation (36.1% vs. 4.8%). In conclusion, abnormal FVC is common in young patients after the Fontan procedure and is independently associated with reduced exercise capacity. A large subset has a pathologically low breathing reserve, consistent with a pulmonary mechanical contribution to exercise limitation.
- Published
- 2014
31. Measuring central pulmonary pressures during exercise in COPD: how to cope with respiratory effects
- Author
-
Bart Boerrigter, Aaron B. Waxman, David M. Systrom, Anton Vonk-Noordegraaf, Nico Westerhof, Pulmonary medicine, Physiology, and ICaR - Heartfailure and pulmonary arterial hypertension
- Subjects
Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Time Factors ,Hypertension, Pulmonary ,Hemodynamics ,Pulmonary Artery ,Pulmonary Disease, Chronic Obstructive ,Oxygen Consumption ,Forced Expiratory Volume ,medicine.artery ,Internal medicine ,Pressure ,Humans ,Medicine ,Pulmonary Wedge Pressure ,Expiration ,Respiratory system ,Pulmonary wedge pressure ,Exercise ,Aged ,COPD ,business.industry ,Respiration ,Limits of agreement ,Central venous pressure ,Reproducibility of Results ,Middle Aged ,Respiration Disorders ,medicine.disease ,Surgery ,Pulmonary artery ,Cardiology ,Female ,business - Abstract
Respiratory influences are major confounders when evaluating central haemodynamics during exercise. We studied four different methods to assess mean pulmonary artery pressure (mPAP) and pulmonary capillary wedge pressure (PCWP) in cases of respiratory swings. Central haemodynamics were measured simultaneously with oesophageal pressure during exercise in 30 chronic obstructive pulmonary disease (COPD) patients. mPAP and PCWP were assessed at the end of expiration, averaged over the respiratory cycle and corrected for the right atrial pressure (RAP) waveform estimated intrathoracic pressure, and compared with the transmural pressures. Bland-Altman analyses showed the best agreement of mPAP averaged over the respiratory cycle (bias (limits of agreement) 2.5 (-6.0-11.8) mmHg) and when corrected with the nadir of RAP (-3.6 (-11.2-3.9) mmHg). Measuring mPAP at the end of expiration (10.3 (0.5-20.3) mmHg) and mPAP corrected for the RAP swing (-9.3 (-19.8-2.1) mmHg) resulted in lower levels of agreement. The respiratory swings in mPAP and PCWP were similar (r(2)=0.82, slope ± se 0.95 ± 0.1). Central haemodynamics measured at the end of expiration leads to an overestimation of intravascular pressures in exercising COPD patients. Good measurement can be acquired even when oesopghageal pressure is omitted, by averaging pressures over the respiratory cycle or using the RAP waveform to correct for intrathoracic pressure. Assessment of the pulmonary gradient is unaffected by respiratory swings.
- Published
- 2013
32. Pulmonary haemodynamics during recovery from maximum incremental cycling exercise
- Author
-
Manyoo Agarwal, Aaron B. Waxman, Roza Badr Eslam, Rudolf K.F. Oliveira, and David M. Systrom
- Subjects
Pulmonary and Respiratory Medicine ,Cardiac function curve ,Male ,medicine.medical_specialty ,Hypertension, Pulmonary ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Internal medicine ,medicine.artery ,medicine ,Humans ,Pulmonary Wedge Pressure ,Pulmonary wedge pressure ,Exercise ,Aged ,Exercise Tolerance ,business.industry ,Hemodynamic Monitoring ,Erythropoietin-producing hepatocellular (Eph) receptor ,Stroke Volume ,Stroke volume ,Middle Aged ,medicine.disease ,Pulmonary hypertension ,Surgery ,medicine.anatomical_structure ,030228 respiratory system ,Echocardiography ,Pulmonary artery ,Cardiology ,Vascular resistance ,Exercise Test ,Pulmonary venous hypertension ,Female ,Vascular Resistance ,business - Abstract
Assessment of cardiac function during exercise can be technically demanding, making the recovery period a potentially attractive diagnostic window. However, the validity of this approach for exercise pulmonary haemodynamics has not been validated.The present study, therefore, evaluated directly measured pulmonary haemodynamics during 2-min recovery after maximum invasive cardiopulmonary exercise testing in patients evaluated for unexplained exertional intolerance. Based on peak exercise criteria, patients with exercise pulmonary hypertension (ePH; n=36), exercise pulmonary venous hypertension (ePVH; n=28) and age-matched controls (n=31) were analysed.By 2-min recovery, 83% (n=30) of ePH patients had a mean pulmonary artery pressure (mPAP) In conclusion, we observed that mPAP and PAWP decay quickly during recovery in ePH and ePVH, compromising the sensitivity of recovery haemodynamic measurements in diagnosing pulmonary hypertension. ePH and ePVH had different PVR and PVC recovery patterns, suggesting differences in the underlying pulmonary hypertension pathophysiology.
- Published
- 2016
33. Skeletal Muscle Mitochondrial Function Is Associated with Longitudinal Growth Velocity in Children and Adolescents
- Author
-
Loredana Farilla, Amy Fleischman, Steven K. Grinspoon, Meaghan A. McCarthy, Shana E. McCormack, David M. Systrom, and Mirko I. Hrovat
- Subjects
Blood Glucose ,Male ,Aging ,medicine.medical_specialty ,Adolescent ,Phosphocreatine ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Context (language use) ,Growth ,Biology ,Hot Topics in Translational Endocrinology ,Biochemistry ,Body Mass Index ,Cohort Studies ,chemistry.chemical_compound ,Adenosine Triphosphate ,Endocrinology ,Insulin resistance ,Internal medicine ,medicine ,Homeostasis ,Humans ,Glucose homeostasis ,Longitudinal Studies ,Insulin-Like Growth Factor I ,Child ,Gonadal Steroid Hormones ,Muscle, Skeletal ,Exercise ,Sex Characteristics ,Glucose tolerance test ,medicine.diagnostic_test ,Puberty ,Biochemistry (medical) ,Skeletal muscle ,Glucose Tolerance Test ,medicine.disease ,Magnetic Resonance Imaging ,Mitochondria, Muscle ,medicine.anatomical_structure ,chemistry ,Female ,Insulin Resistance ,Energy Intake ,Body mass index ,Cohort study - Abstract
Periods of rapid growth require an increase in energy use and substrate formation. Mitochondrial function contributes to each of these and therefore may play a role in longitudinal growth.Twenty-nine children and adolescents of ages 8-15 yr were enrolled in a comprehensive longitudinal assessment of glucose homeostasis and mitochondrial function. Fasting laboratory studies and an estimate of mitochondrial function (as assessed by the time to recovery of phosphocreatine (PCr) concentration after submaximal quadriceps extension/flexion exercise using (31)P magnetic resonance spectroscopy) were obtained at baseline and annually for 2 yr.Data were complete for 23 subjects. Subjects were 11.3 ± 1.9 (sd) yr old at the beginning of the study; 61% were male. Average annualized growth velocity at 1 yr for boys was 7.1 ± 1.5 cm/yr and for girls 6.5 ± 1.7 cm/yr. More rapid recovery of PCr concentration, suggestive of greater skeletal muscle oxidative phosphorylation capacity at baseline, was associated with faster growth velocity in the subsequent year (r(2) = 0.29; P = 0.008). In multivariate modeling, baseline mitochondrial function remained significantly and independently associated with growth (R(2) for model = 0.51; P = 0.05 for effect of phosphocreatine recovery time constant), controlling for age, gender, Tanner stage, body mass index Z-score, and height Z-score.We report a novel association between time to recovery of PCr concentration after submaximal exercise and faster annual linear growth in healthy children. Future studies are needed to determine the physiological mechanisms and clinical consequences of this observation.
- Published
- 2011
34. Determinants of Ventilatory Efficiency in Heart Failure
- Author
-
Marc J. Semigran, David M. Systrom, Paul P. Pappagianopolas, Ravi V. Shah, and Gregory D. Lewis
- Subjects
Male ,Pulmonary Circulation ,medicine.medical_specialty ,Sildenafil ,Hypertension, Pulmonary ,Vasodilator Agents ,Hemodynamics ,Radionuclide ventriculography ,Article ,Muscle, Smooth, Vascular ,Piperazines ,Sildenafil Citrate ,Cohort Studies ,chemistry.chemical_compound ,Double-Blind Method ,Ventriculography, First-Pass ,Internal medicine ,medicine ,Humans ,Sulfones ,Aged ,Heart Failure ,Ejection fraction ,business.industry ,Respiration ,Carbon Dioxide ,Middle Aged ,medicine.disease ,Pulmonary hypertension ,medicine.anatomical_structure ,chemistry ,Purines ,Muscle Tonus ,Heart failure ,Exercise Test ,Ventricular Function, Right ,Breathing ,Vascular resistance ,Cardiology ,Female ,Vascular Resistance ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background— Ventilatory efficiency, right ventricular (RV) function, and secondary pulmonary hypertension are each prognostic indicators in patients with heart failure due to left ventricular systolic dysfunction, but the relationships among these variables have not been comprehensively investigated. In this study, we hypothesized that inefficient ventilation during exercise, as defined by an abnormally steep relationship between ventilation and carbon dioxide output (V e /V co 2 slope), may be a marker of secondary pulmonary hypertension and RV dysfunction in heart failure. Methods and Results— A cohort of patients with systolic heart failure (mean�SD age, 58�13 years; left ventricular ejection fraction, 0.27�0.05; peak oxygen uptake, 11.2�3.2 mL kg −1 min −1 ) underwent incremental cardiopulmonary exercise testing with simultaneous hemodynamic monitoring and first-pass radionuclide ventriculography before and after 12 weeks of treatment with sildenafil, a selective pulmonary vasodilator, or placebo. V e /V co 2 slope was positively related to rest and exercise pulmonary vascular resistance ( R =0.39 and R =0.60, respectively) and rest pulmonary capillary wedge pressure ( R =0.49, P R =−0.29, P =0.03). Over the 12-week study period, V e /V co 2 slope fell 8�3% ( P =0.02) with sildenafil and was unchanged with placebo. Changes in V e /V co 2 slope correlated with changes in exercise pulmonary vascular resistance ( R =0.69, P R =−0.58 and −0.40, respectively, both P Conclusions— In patients with systolic heart failure and secondary pulmonary hypertension, ventilatory efficiency is closely related to RV function and pulmonary vascular tone during exercise.
- Published
- 2008
35. Impaired Systemic Oxygen Extraction at Maximum Exercise in Pulmonary Hypertension
- Author
-
Aaron B. Waxman, James J. Tolle, and David M. Systrom
- Subjects
Male ,Pulmonary Circulation ,medicine.medical_specialty ,Systole ,Hypertension, Pulmonary ,Vasodilator Agents ,Physical Therapy, Sports Therapy and Rehabilitation ,Physical exercise ,Vasodilation ,Fick principle ,Ventricular Dysfunction, Left ,Oxygen Consumption ,Internal medicine ,Humans ,Vasoconstrictor Agents ,Medicine ,Orthopedics and Sports Medicine ,Prospective Studies ,Muscle, Skeletal ,Exercise ,Exercise Tolerance ,Lung ,business.industry ,Respiratory disease ,Middle Aged ,medicine.disease ,Pulmonary hypertension ,Mitochondria ,Surgery ,Oxygen ,Perfusion ,Blood pressure ,medicine.anatomical_structure ,Exercise Test ,Cardiology ,Female ,business - Abstract
To determine the relative contributions of the Fick principle variables to impaired exercise tolerance in pulmonary arterial hypertension compared with pulmonary venous hypertension.One hundred forty-seven consecutive, complete, clinically indicated cardiopulmonary exercise tests done with radial and pulmonary arterial catheters and radionuclide ventriculographic scanning were screened for an exercise limit attributable to 1) pulmonary arterial hypertension (N = 34), 2) left ventricular systolic (N = 23), or 3) diastolic dysfunction (N = 36), defined by mean pulmonary artery pressure, pulmonary capillary wedge pressure, and left ventricular ejection fraction. Systolic and diastolic dysfunction are together referred to as pulmonary venous hypertension. Patients with other limits were excluded, including those with a pulmonary mechanical limit. For the resulting 93 exercise tests, the Fick principle variables' contributions to a depressed maximum oxygen consumption were compared by ANOVA and ANCOVA.Maximum oxygen consumption (54.5 +/- 15.5 vs 73.2 +/- 20.1 vs 66.0 +/- 15.7% predicted) and oxygen delivery (1457 +/- 456 vs 2161 +/- 824 vs 2007 +/- 665 mL x min(-1)) were reduced in systolic dysfunction versus both diastolic dysfunction and pulmonary arterial hypertension, respectively (P0.05 by ANOVA). Maximum systemic oxygen extraction ratio was highest in systolic dysfunction, intermediate in diastolic dysfunction, and lowest in pulmonary arterial hypertension (0.744 +/- 0.091 vs 0.680 +/- 0.091 vs 0.619 +/- 0.113, respectively, P0.05 among all groups). Systemic oxygen extraction at peak exercise was inversely related to maximum cardiac output in pulmonary arterial hypertension, but it was blunted versus systolic dysfunction throughout the range of peak cardiac outputs (P0.05 by ANCOVA).Maximum systemic oxygen extraction is impaired in pulmonary arterial versus pulmonary venous hypertension and contributes to the exercise limit.
- Published
- 2008
36. Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochondrial function in muscle of healthy adults
- Author
-
Walter R. Frontera, Christian T. Farrar, David M. Systrom, Steven K. Grinspoon, Mirko I. Hrovat, Kathleen V. Fitch, Bijoy J. Thomas, Martin Torriani, Stine Johnsen, Hélène C. F. Côté, and Amy Fleischman
- Subjects
Adult ,Male ,medicine.medical_specialty ,Magnetic Resonance Spectroscopy ,Phosphocreatine ,Physiology ,Endocrinology, Diabetes and Metabolism ,Type 2 diabetes ,Biology ,DNA, Mitochondrial ,Article ,Nucleoside Reverse Transcriptase Inhibitor ,Insulin resistance ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Muscle, Skeletal ,Reverse-transcriptase inhibitor ,Stavudine ,Phosphorus ,Middle Aged ,Glucose clamp technique ,Nucleotidyltransferase ,medicine.disease ,Mitochondria, Muscle ,Glucose ,Endocrinology ,Body Composition ,Glucose Clamp Technique ,Reverse Transcriptase Inhibitors ,Female ,Insulin Resistance ,Protons ,Nucleoside ,medicine.drug - Abstract
Mitochondrial dysfunction may contribute to the development of insulin resistance and type 2 diabetes. Nucleoside reverse transcriptase inhibitors (NRTIs), specifically stavudine, are known to alter mitochondrial function in human immunodeficiency virus (HIV)-infected individuals, but the effects of stavudine on glucose disposal and mitochondrial function in muscle have not been prospectively evaluated. In this study, we investigated short-term stavudine administration among healthy control subjects to determine effects on insulin sensitivity. A secondary aim was to determine the effects of stavudine on mitochondrial DNA (mtDNA) and function. Sixteen participants without personal or family history of diabetes were enrolled. Subjects were randomized to receive stavudine, 30–40 mg, twice a day, or placebo for 1 mo. Insulin sensitivity determined by glucose infusion rate during the hyperinsulinemic euglycemic clamp was significantly reduced after 1-mo exposure in the stavudine-treated subjects compared with placebo (−0.8 ± 0.5 vs. +0.7 ± 0.3 mg·kg−1·min−1, P = 0.04, stavudine vs. placebo). In addition, muscle biopsy specimens in the stavudine-treated group showed significant reduction in mtDNA/nuclear DNA (−52%, P = 0.005), with no change in placebo-treated subjects (+8%, P = 0.9).31P magnetic resonance spectroscopy (MRS) studies of mitochondrial function correlated with insulin sensitivity measures ( r2= 0.5, P = 0.008). These findings demonstrate that stavudine administration has potent effects on insulin sensitivity among healthy subjects. Further studies are necessary to determine whether changes in mtDNA resulting from stavudine contribute to effects on insulin sensitivity.
- Published
- 2007
37. Age-related upper limits of normal for maximum upright exercise pulmonary haemodynamics
- Author
-
Aaron B. Waxman, Abbey L. Karin, Alexander R. Opotowsky, Julie A. Tracy, Manyoo Agarwal, David M. Systrom, and Rudolf K.F. Oliveira
- Subjects
Pulmonary and Respiratory Medicine ,Adult ,Male ,medicine.medical_specialty ,Cardiac output ,Supine position ,Hypertension, Pulmonary ,Rest ,Population ,030204 cardiovascular system & hematology ,Pulmonary Artery ,03 medical and health sciences ,0302 clinical medicine ,Oxygen Consumption ,Internal medicine ,medicine ,Humans ,Arterial Pressure ,Exercise physiology ,Cardiac Output ,education ,Exercise ,Aged ,education.field_of_study ,Exercise Tolerance ,business.industry ,Hemodynamics ,Stroke Volume ,Stroke volume ,Middle Aged ,medicine.disease ,Pulmonary hypertension ,Surgery ,Bicycling ,Blood pressure ,medicine.anatomical_structure ,030228 respiratory system ,Cardiology ,Vascular resistance ,Exercise Test ,Female ,Vascular Resistance ,business - Abstract
The exercise definition of pulmonary hypertension was eliminated from the pulmonary hypertension guidelines in part due to uncertainty of the upper limits of normal (ULNs) for exercise haemodynamics in subjects >50 years old.The present study, therefore, evaluated the pulmonary haemodynamic responses to maximum upright incremental cycling exercise in consecutive subjects who underwent an invasive cardiopulmonary exercise testing for unexplained exertional intolerance, deemed normal based on preserved exercise capacity and normal resting supine haemodynamics. Subjects aged >50 years old (n=41) were compared with subjects ≤50 years old (n=25). ULNs were calculated as mean+2sd.Peak exercise mean pulmonary arterial pressure was not different for subjects >50 and ≤50 years old (23±5versus22±4 mmHg, p=0.22), with ULN of 33 and 30 mmHg, respectively. Peak cardiac output was lower in older subjects (median (interquartile range): 12.1 (9.4–14.2)versus16.2 (13.8–19.2) L·min−1, psd: 1.20±0.45versus0.82±0.26 Wood units, pWe observed that subjects >50 and ≤50 years old have different pulmonary vascular responses to exercise. Older subjects have higher pulmonary vascular resistance at peak exercise, resulting in different exercise haemodynamics ULNs compared with the younger population.
- Published
- 2015
38. Diagnosis of pulmonary vascular limit to exercise by cardiopulmonary exercise testing
- Author
-
Deborah H. Markowitz and David M. Systrom
- Subjects
Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Anaerobic Threshold ,Hypertension, Pulmonary ,Physical exercise ,Internal medicine ,medicine ,Humans ,Aged ,Transplantation ,Lung ,Pulmonary Gas Exchange ,business.industry ,Lactate threshold ,Respiratory disease ,VO2 max ,Middle Aged ,medicine.disease ,Pulmonary hypertension ,Surgery ,medicine.anatomical_structure ,Exercise Test ,Cardiology ,Vascular resistance ,Female ,Pulmonary Ventilation ,Cardiology and Cardiovascular Medicine ,business ,Algorithms - Abstract
Given the recent development of newer and less-invasive treatments for pulmonary hypertension, and the long wait for lung transplantation, early and correct diagnosis of this condition is increasingly important. The purpose of this study was to determine and improve the accuracy of a non-invasive, cardiopulmonary exercise-testing algorithm for detecting a pulmonary vascular limit to exercise.We performed 130 consecutive, incremental cycling-exercise tests for exertional symptoms with pulmonary and radial artery catheters in place. Pulmonary vascular limit was defined as pulmonary vascular resistance at maximum exercise120 dynes. sec/cm(5) and a peak-exercise systemic oxygen delivery80% predicted, without a pulmonary mechanical limit or poor effort. We applied a previously reported non-invasive exercise-test-interpretation algorithm to each patient and sequentially manipulated branch point threshold values to maximize accuracy.The sensitivity of the original non-invasive algorithm for pulmonary vascular limit was 79%, specificity was 75%, and accuracy was 76%. Sensitivity did not change with systematic alteration of branch-point threshold values, but specificity and accuracy improved to 88% and 85%, respectively. Accuracy improved most by modifying the threshold values for percent predicted maximum oxygen uptake and carbon dioxide output ventilatory equivalents at lactate threshold.Non-invasive cardiopulmonary exercise testing is a useful tool for detecting and excluding a pulmonary vascular limit and for determining whether abnormal pulmonary hemodynamics limit aerobic capacity.
- Published
- 2004
39. An Elevated Breathing Reserve Index at the Lactate Threshold Is a Predictor of Mortality in Patients with Cystic Fibrosis Awaiting Lung Transplantation
- Author
-
David M. Systrom, Leo C. Ginns, and Kelan G. Tantisira
- Subjects
Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Time Factors ,Anaerobic Threshold ,Cystic Fibrosis ,Waiting Lists ,medicine.medical_treatment ,Critical Care and Intensive Care Medicine ,Incremental exercise ,Pulmonary function testing ,Oxygen Consumption ,Predictive Value of Tests ,Risk Factors ,Forced Expiratory Volume ,Internal medicine ,medicine ,Humans ,Lung transplantation ,Lactic Acid ,Proportional Hazards Models ,Lung ,business.industry ,Lactate threshold ,Survival Analysis ,Surgery ,Transplantation ,medicine.anatomical_structure ,Multivariate Analysis ,Breathing ,Cardiology ,Female ,business ,Respiratory minute volume ,Boston ,Follow-Up Studies ,Lung Transplantation - Abstract
The proportion of cystic fibrosis (CF) patients dying while on the lung transplant wait list remains high; identification of such patients remains difficult. The breathing reserve index (BRI = minute ventilation/maximal voluntary ventilation) at the lactate threshold (LT) is a predictor of a pulmonary mechanical limit to incremental exercise. We hypothesized that an elevated BRI at the LT in patients with CF awaiting lung transplantation would be a predictor of wait list mortality. Forty-five consecutive patients with CF completed cardiopulmonary exercise testing as part of their pretransplant assessment. We evaluated BRI at LT, baseline demographic characteristics, pulmonary function, and other exercise parameters via Cox proportional hazards modeling. Fifteen patients died while awaiting transplant. Twenty one were transplanted, and nine still awaited transplantation. Relative risks from the multivariate model included (95% confidence interval in parentheses) BRI at LT, 17.52 (2.45-123.97); resting Pa(CO(2)), 1.29 (1.10-1.49); resting Pa(O(2)), 0.97 (0.90-1.05); and forced expiratory volume at one second as a percent of predicted, 1.19 (1.05-1.34). BRI at LT not only provided the highest point estimate of risk for wait list mortality but also identified a physiologically significant threshold value (0.70 or more) for those at risk. This measurement may allow improved timing of listing for transplantation, including consideration for living donor transplantation.
- Published
- 2002
40. Inadequate venous return as a primary cause for Fontan circulatory limitation
- Author
-
Dan G. Halpern, Alexander R. Opotowsky, David M. Systrom, Thomas J. Kulik, and Fred M. Wu
- Subjects
Pulmonary and Respiratory Medicine ,Adult ,Heart Defects, Congenital ,medicine.medical_specialty ,Fontan Procedure ,law.invention ,Veins ,law ,Internal medicine ,Vasoplegia ,medicine ,Cardiopulmonary bypass ,Humans ,Treatment Failure ,Thrombus ,Transplantation ,business.industry ,medicine.disease ,Thrombosis ,Dissection ,Circulatory system ,Cardiology ,Surgery ,Female ,Cardiology and Cardiovascular Medicine ,business ,Venous return curve - Abstract
graft would have allowed a more limited surgical sub-costal approach for LVAD pump exchange. This may have avoided the extensive dissection, prolonged cardiopulmonary bypass (CBP) duration and vasoplegia, which ultimately resulted in the patient’s death. The diagnosis of LVAD thrombosis is complex and should be based on an algorithm that includes clinical symptoms, along with serologic and imaging studies. CTA is considered a non-invasive imaging modality and may be a reliable diagnostic tool for thrombus detection in the graft; however, clinicians should be aware of the potential misinterpretation of findings in VAD patients.
- Published
- 2014
41. Respiratory sensations during heavy exercise in subjects without respiratory chemosensitivity
- Author
-
David M. Systrom, Steven Shea, Daniel C. Shannon, Robert B. Banzett, and Christina M. Spengler
- Subjects
Adult ,Male ,Pulmonary and Respiratory Medicine ,Adolescent ,Physiology ,Physical exercise ,Hyperpnea ,Congenital central hypoventilation syndrome ,Sleep Apnea Syndromes ,medicine ,Humans ,Lactic Acid ,Respiratory system ,Exercise ,business.industry ,Respiration ,Respiratory disease ,Respiratory center ,Carbon Dioxide ,respiratory system ,medicine.disease ,Chemoreceptor Cells ,Anesthesia ,Muscle Fatigue ,Breathing ,Female ,medicine.symptom ,Pulmonary Ventilation ,business ,Hypercapnia - Abstract
Breathlessness arises from increased medullary respiratory center activity projecting to the forebrain (respiratory corollary discharge hypothesis). Subjects with congenital central hypoventilation syndrome (CCHS) lack the normal hyperpnea and breathlessness during hypercapnia. The corollary discharge hypothesis predicts that if CCHS subjects have normal hyperpnea during exercise, they will experience normal breathlessness during exercise. To test this, we studied four CCHS subjects and six matched controls during an exhausting constant-load cycling test requiring substantial anaerobiosis. CCHS subjects rated significantly less breathlessness at the end of the test than controls, but ventilation (index of respiratory corollary discharge) was also somewhat lower in CCHS (not significant). In both groups, breathlessness increased disproportionately more than ventilation towards the end of exercise. These data failed to disprove the corollary discharge hypothesis of breathlessness, but do suggest that the relationship between ventilation and breathlessness is non-linear and/or that projections of chemoreceptor afferents to the forebrain (presumed lacking in CCHS) is one source of breathlessness in normals.
- Published
- 1998
42. Maximum Cardiac Output During Incremental Exercise by First-pass Radionuclide Ventriculography
- Author
-
Paul P. Pappagianopoulos, David A. Oelberg, Charles A. Boucher, David M. Systrom, and Jaman Maroni
- Subjects
Lung Diseases ,Pulmonary and Respiratory Medicine ,Cardiac Catheterization ,Cardiac output ,Heart Diseases ,Heart Ventricles ,medicine.medical_treatment ,Radionuclide ventriculography ,Critical Care and Intensive Care Medicine ,Fick principle ,Incremental exercise ,Ventriculography, First-Pass ,Humans ,Ventricular Function ,Medicine ,Cardiac Output ,Exercise ,Cardiac catheterization ,business.industry ,Pulmonary artery catheter ,Blood flow ,Middle Aged ,Respiratory Function Tests ,Ventricular Function, Right ,Breathing ,Cardiology and Cardiovascular Medicine ,business ,Nuclear medicine - Abstract
Study objective To validate a noninvasive first-pass radionuclide ventriculographic (FPRV) measurement of maximum cardiac output (Qv) during exercise. Design Comparison of Qv to that measured by the Fick principle (Qf) at peak exercise. Setting Academic cardiopulmonary exercise laboratory. Patients Seventy-eight consecutive patients without a history of septal defect undergoing clinically indicated maximum incremental cardiopulmonary exercise testing with pulmonary arterial catheterization and FPRV. Measurements and results Ventilation and gas exchange were measured breath-by-breath or by a mixing chamber/mass spectrometer system. Arterial and mixed venous O 2 content were measured each minute during exercise. When patients without left-to-right ventricular stroke count ratio evidence for left-sided regurgitation were isolated, peak Qv was linearly related to Qf (r=0.75, p=0.0001). To account for a small systematic overestimation (bias) of Qf by Qv, the linear equation for the Qv/Qf relation was derived for patients studied between 1990 and 1993 and applied to those studied subsequently. The resulting corrected peak Qv was tightly related to peak Qf (r=0.90, p Conclusion FPRV can reasonably estimate maximum cardiac output during incremental exercise in patients for whom the technique has ruled out left-sided cardiac regurgitant lesions.
- Published
- 1998
43. Systemic oxygen extraction during incremental exercise in patients with severe chronic obstructive pulmonary disease
- Author
-
Deborah H. Markowitz, Leo C. Ginns, David M. Systrom, Benjamin D. Medoff, Paul P. Pappagianopoulos, and David A. Oelberg
- Subjects
Male ,medicine.medical_specialty ,Physiology ,Radionuclide ventriculography ,Physical exercise ,Incremental exercise ,Oxygen Consumption ,Physiology (medical) ,Internal medicine ,Humans ,Medicine ,Orthopedics and Sports Medicine ,Lung Diseases, Obstructive ,Exercise physiology ,Exercise ,Aged ,COPD ,business.industry ,Lactate threshold ,Hemodynamics ,Public Health, Environmental and Occupational Health ,General Medicine ,Middle Aged ,medicine.disease ,Respiratory Function Tests ,Surgery ,Exercise Test ,Cardiology ,Arterial blood ,Acidosis, Lactic ,Female ,Blood Gas Analysis ,business ,Respiratory minute volume - Abstract
To determine if decreased systemic oxygen (O2) extraction contributes to the exercise limit in severe chronic obstructive pulmonary disease (COPD), 40 consecutive incremental cycle ergometer exercise tests performed by such patients, from which a "log-log" lactate threshold (LT) was identified, were compared to those of 8 patients with left ventricular failure (LVF) and 10 normal controls. Pulmonary gas exchange and minute ventilation were measured continuously and arterial blood gas tensions, pH, and lactate concentrations were sampled each minute. Cardiac output (Qc) was measured by first-pass radionuclide ventriculography. The systemic O2 extraction ratio (O2ER) was calculated as arterial - mixed venous O2 content difference (CaO2 - CvO2)/CaO2. Peak exercise O2 uptake (VO2peak) was markedly reduced in both COPD and LVF [41 (3) and 42 (3)% predicted, respectively], compared to controls [89 (2)% predicted, P0.0001 for each]. Similarly, the LT occurred at a low percentage of predicted maximal oxygen consumption in both COPD and LVF [25 (2) and 27 (3)%] compared to normals [46 (3)%, P0.0001 for each]. The systemic O2ER at peak exercise was severely reduced in COPD [0.36 (0.02)] compared to the other groups [P0.0001 for each], for whom it was nearly identical [0.58 (0.03) vs 0.63 (0.04), LVF vs control, P0.05]. In the COPD group, an early LT correlated with reduced systemic O2ER at peak exercise (r = 0.64, P0.0001), but not with any index of systemic O2 delivery. These data suggest that lactic acidemia during exercise in patients with severe COPD is better related to abnormal systemic O2 extraction than to its delivery and contributes to the exercise limit.
- Published
- 1998
44. A cardiopulmonary study of lisdexamfetamine in adults with attention-deficit/hyperactivity disorder
- Author
-
Rachel Shelley-Abrahamson, Aaron L. Baggish, Paul Hammerness, Mary Schillinger, Randall M. Zusman, Craig B. H. Surman, Timothy E. Wilens, and David M. Systrom
- Subjects
Adult ,Male ,Dextroamphetamine ,medicine.medical_treatment ,Diastole ,Heart Rate ,Statistical significance ,Heart rate ,medicine ,Attention deficit hyperactivity disorder ,Humans ,Exertion ,Prospective Studies ,Lisdexamfetamine Dimesylate ,Prospective cohort study ,Biological Psychiatry ,Heart ,Middle Aged ,medicine.disease ,Stimulant ,Psychiatry and Mental health ,Lisdexamfetamine ,Attention Deficit Disorder with Hyperactivity ,Echocardiography ,Anesthesia ,Case-Control Studies ,Hypertension ,Exercise Test ,Central Nervous System Stimulants ,Female ,Psychology ,medicine.drug - Abstract
Due to concerns about the safety of stimulants for ADHD, novel assessments of the cardiopulmonary impact of these agents are needed.An open design of lisdexamfetamine (LDX) in 15 adults with DSM-IV ADHD. Following a psychiatric evaluation and medical history, subjects underwent echocardiography (TTE) and cardiopulmonary exercise testing (CPET). LDX was titrated to 70 mg daily over 6 weeks, followed by monthly visits to 6 months. Change in TTE and CPET measures were examined following up to 6 months of LDX.At endpoint, there were no significant alterations in indices of cardiac systolic performance, or in metabolic and ventilatory variables at maximum exertion (P values0.05). We found significant mean changes in resting LV systolic dimension and Doppler diastolic indices. Change in heart rate recovery at 1 min met statistical significance (P = 0.05).We did not detect clinically meaningful changes in cardiac structure and function or in metabolic and ventilatory variables at maximum exertion in ADHD adults receiving open LDX. The clinical significance of changes in resting LV dimension and indices of diastolic function are not in the direction of cardiomyopathy. Future large sample controlled study can examine these findings, as well as stimulants' impact on heart rate recovery.
- Published
- 2012
45. Expiratory flow pattern following single-lung transplantation in emphysema
- Author
-
Reginald Greene, John C. Wain, Leo C. Ginns, Jose G. Venegas, James P. Herlihy, Kenneth A. McKUSICK, and David M. Systrom
- Subjects
Male ,Pulmonary and Respiratory Medicine ,Spirometry ,medicine.medical_specialty ,medicine.medical_treatment ,Anastomosis ,Critical Care and Intensive Care Medicine ,Internal medicine ,Bronchoscopy ,medicine ,Humans ,Lung transplantation ,Lung volumes ,Postoperative Period ,Maximal Expiratory Flow-Volume Curves ,Lung ,medicine.diagnostic_test ,business.industry ,Respiratory disease ,Middle Aged ,respiratory system ,medicine.disease ,MEFV ,respiratory tract diseases ,Surgery ,Transplantation ,medicine.anatomical_structure ,Pulmonary Emphysema ,Linear Models ,Respiratory Mechanics ,Cardiology ,Female ,Tomography, X-Ray Computed ,business ,Follow-Up Studies ,Lung Transplantation - Abstract
In single lung transplantation (SLT) recipients, a "plateau" of the maximal expiratory flow volume curve (MEFV) and a "biphasic" MEFV have been reported to reflect anastomosis pathology. A plateau is defined as constant airflow over a large expired volume early in the MEFV. A biphasic MEFV has an initial period of high flow followed by a terminal low flow phase. Models of expiratory flow limitation by wave speed, however, predict that the MEFV of SLT recipients with emphysema should both be biphasic and demonstrate a plateau even without anastomosis pathology. Review of the spirometries and clinical courses of our first ten patients receiving SLT for emphysema demonstrated a biphasic MEFV, and a plateau of the MEFV in all patients. No patient showed evidence of anastomosis pathology. Independent lung spirometries, generated by a novel technique, revealed that the initial high flow phase of the MEFV came from the transplanted lung and the terminal low flow from the native emphysematous lung. The location of the flow limitation was demonstrated to be immediately downstream from the anastomosis. Therefore, the MEFV of SLT recipients with emphysema routinely demonstrates both a biphasic pattern and a plateau, neither of which necessarily reflect anastomosis pathology.
- Published
- 1994
46. Dietary effects on exercising muscle metabolism and performance by 31P-MRS
- Author
-
R. S. Fishman, R. L. Hesslink, D. E. Larson, M. I. Hrovat, and David M. Systrom
- Subjects
Adult ,Male ,medicine.medical_specialty ,Magnetic Resonance Spectroscopy ,Physiology ,Respiratory physiology ,Phosphates ,Phosphocreatine ,chemistry.chemical_compound ,Oxygen Consumption ,Physiology (medical) ,Internal medicine ,Dietary Carbohydrates ,medicine ,Humans ,Respiratory system ,Exercise physiology ,Muscle, Skeletal ,Exercise ,Respiratory exchange ratio ,Chemistry ,Skeletal muscle ,Dietary Fats ,Diet ,Endocrinology ,medicine.anatomical_structure ,Biochemistry ,Respiratory Mechanics ,Breathing ,Female ,Energy Metabolism ,Respiratory minute volume - Abstract
To determine how diet modulates short-term exercise capacity, skeletal muscle pH and bioenergetic state were examined by 31P-magnetic resonance spectroscopy in nine healthy volunteers. Subjects performed incremental quadriceps exercise to exhaustion after 5 days of high-carbohydrate (HCHO) or high-fat (HFAT) diet randomly assigned in crossover fashion and separated by a 2.5-day period of ad libitum mixed diet. Simultaneous measurements were made of pulmonary gas exchange, minute ventilation, and quadriceps muscle pH and phosphorylation potential. At rest and peak exercise, respiratory exchange ratio and minute ventilation were higher after HCHO than after HFAT (P < 0.05), reflecting greater CHO utilization. Peak O2 consumption (VO2) was not increased after HCHO (P > 0.05), but exercise duration was (339 +/- 34 s for HCHO vs. 308 +/- 25 s for HFAT; P < 0.05). HCHO was associated with a blunted early fall of phosphocreatine (PCr)/Pi vs. VO2 (-4.1 +/- 0.7 x 10(-2) min/ml for HCHO vs. -5.6 +/- 1.2 x 10(-2) min/ml for HFAT; P < 0.05). On both study days, the slope of PCr/Pi vs. VO2, before and after the PCr threshold, was correlated with exercise time. The results suggest that a diet rich in CHO improves exercise efficiency through beneficial effects on intracellular phosphorylation potential.
- Published
- 1994
47. Exercise Oscillatory Ventilation in Systolic Heart Failure: An Indicator of Impaired Hemodynamic Response to Exercise
- Author
-
Paul P. Pappagianopoulos, Marc J. Semigran, Stacyann S. Hough, Ravi V. Shah, Ryan M. Murphy, Gregory D. Lewis, Rajeev Malhotra, and David M. Systrom
- Subjects
Male ,Cardiac output ,Rest ,Physical Exertion ,Article ,Piperazines ,Sildenafil Citrate ,Predictive Value of Tests ,Physiology (medical) ,medicine ,Ventricular Pressure ,Humans ,Pulmonary Wedge Pressure ,Sulfones ,Cardiac Output ,Pulmonary wedge pressure ,Ejection fraction ,business.industry ,Pulmonary Gas Exchange ,Stroke Volume ,Stroke volume ,Carbon Dioxide ,Middle Aged ,Phosphodiesterase 5 Inhibitors ,medicine.disease ,Oxygen ,Purines ,Heart failure ,Anesthesia ,Breathing ,Ventricular pressure ,Exercise Test ,Respiratory Mechanics ,Arterial blood ,Female ,Blood Gas Analysis ,Cardiology and Cardiovascular Medicine ,business ,Heart Failure, Systolic - Abstract
Background— Exercise oscillatory ventilation (EOV) is a noninvasive parameter that potently predicts outcomes in systolic heart failure (HF). However, mechanistic insights into EOV have been limited by the absence of studies relating EOV to invasive hemodynamic measurements and blood gases performed during exercise. Methods and Results— Fifty-six patients with systolic HF (mean±SEM age, 59±2 years; left ventricular ejection fraction, 30±1%) and 19 age-matched control subjects were studied with incremental cardiopulmonary exercise testing. Fick cardiac outputs, filling pressures, and arterial blood gases were measured at 1-minute intervals during exercise. We detected EOV in 45% of HF (HF+EOV) patients and in none of the control subjects. The HF+EOV group did not differ from the HF patients without EOV (HF−EOV) in age, sex, body mass index, left ventricular ejection fraction, or origin of HF. Univariate predictors of the presence of EOV in HF, among measurements performed during exercise, included higher right atrial pressure and pulmonary capillary wedge pressure and lower cardiac index (CI) but not Pa co 2 or Pa o 2 . Multivariate logistic regression identified that low exercise CI is the strongest predictor of EOV (odds ratio, 1.39 for each 1.0-L · min −1 · m −2 decrement in CI; 95% confidence interval, 1.14–1.70; P =0.001). Among HF patients with EOV, exercise CI was inversely related to EOV cycle length ( R =−0.71) and amplitude ( R =−0.60; both P Conclusion— Exercise oscillatory ventilation is closely related to reduced CI and elevated filling pressures during exercise and may be an important surrogate for exercise-induced hemodynamic impairment in HF patients. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00309790.
- Published
- 2011
48. Pulmonary vascular response patterns during exercise in left ventricular systolic dysfunction predict exercise capacity and outcomes
- Author
-
Rajeev Malhotra, Ravi V. Shah, Ryan M. Murphy, Marc J. Semigran, David M. Systrom, Gregory D. Lewis, Kenneth D. Bloch, and Paul P. Pappagianopoulos
- Subjects
Male ,medicine.medical_specialty ,Poor prognosis ,Pulmonary Circulation ,Systole ,Hemodynamics ,Pulmonary Artery ,Article ,Ventricular Dysfunction, Left ,Internal medicine ,medicine.artery ,Medicine ,Humans ,Aged ,Ejection fraction ,Exercise Tolerance ,business.industry ,Exercise capacity ,Middle Aged ,medicine.disease ,Prognosis ,Pulmonary hypertension ,Surgery ,Pulmonary Veins ,Heart failure ,Pulmonary artery ,Cardiology ,Exercise Test ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background— Elevated resting pulmonary arterial pressure (PAP) in patients with left ventricular systolic dysfunction (LVSD) purports a poor prognosis. However, PAP response patterns to exercise in LVSD and their relationship to functional capacity and outcomes have not been characterized. Methods and Results— Sixty consecutive patients with LVSD (age 60±12 years, left ventricular ejection fraction 0.31±0.07, mean±SD) and 19 controls underwent maximum incremental cardiopulmonary exercise testing with simultaneous hemodynamic monitoring. During low-level exercise (30 W), LVSD subjects, compared with controls, had greater augmentation in mean PAPs (15±1 versus 5±1 mm Hg), transpulmonary gradients (5±1 versus 1±1 mm Hg), and effective pulmonary artery elastance (0.05±0.02 versus −0.03±0.01 mm Hg/mL, P P o 2 (10.6±2.6 versus 13.1±4.0 mL · kg −1 · min −1 , P =0.005), lower right ventricular stroke work index augmentation with exercise (5.7±3.8 versus 9.7±5.0 g/m 2 , P =0.002), and increased mortality (hazard ratio 8.1, 95% CI 2.7 to 23.8, P Conclusions— A steep increment in PAP during exercise and failure to augment PAP throughout exercise are associated with decreased exercise capacity and survival in patients with LVSD, and may therefore represent therapeutic targets. Clinical Trial Information— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00309790.
- Published
- 2011
49. Increased skeletal muscle phosphocreatine recovery after sub-maximal exercise is associated with increased carotid intima-media thickness
- Author
-
Mirko I. Hrovat, Hideo Makimura, Takara L. Stanley, Jean M. Connelly, Steven K. Grinspoon, Linda C. Hemphill, Noelle Sun, and David M. Systrom
- Subjects
Tunica media ,Adult ,Carotid Artery Diseases ,Male ,medicine.medical_specialty ,Phosphocreatine ,Physical exercise ,Article ,chemistry.chemical_compound ,Internal medicine ,medicine ,Humans ,cardiovascular diseases ,Muscle, Skeletal ,business.industry ,Skeletal muscle ,Anatomy ,Middle Aged ,Tunica intima ,Lipids ,Mitochondria, Muscle ,medicine.anatomical_structure ,Carotid Arteries ,Intima-media thickness ,chemistry ,Cardiovascular Diseases ,Circulatory system ,Cardiology ,Exercise Test ,Female ,Cardiology and Cardiovascular Medicine ,business ,Tunica Intima ,Tunica Media ,Artery - Abstract
The association between skeletal muscle mitochondrial function and CVD risk in healthy subjects is unknown.Forty subjects were evaluated for CVD risk with lipid profile, oral glucose tolerance test and measurement of carotid intima-media thickness (cIMT). Skeletal muscle mitochondrial function was determined by phosphocreatine recovery after sub-maximal exercise with (31)Phosphorous-MRS and represented as τPCr.τPCr was positively associated with age (r=+0.41; P=0.009) and cIMT (r=+0.50; P=0.001) on univariate analyses. In multivariate regression analysis controlling for age, the association between τPCr and cIMT remained significant (β=0.003; P=0.03). This association remained significant after controlling for traditional risk factors for CVD including age, gender, tobacco use, BMI, blood pressure, cholesterol and fasting glucose in a combined model (β=0.003; P=0.04; R(2)=0.53; P=0.008 for overall model).These data suggest a novel association between skeletal muscle τPCr and increased cIMT, independent of age or traditional CVD risk factors.
- Published
- 2010
50. The impact of moderate-altitude staging on pulmonary arterial hemodynamics after ascent to high altitude
- Author
-
Michael H. Picard, Beth A. Beidleman, Peter J. Fagenholz, Malissa J. Wood, Aaron L. Baggish, David M. Systrom, Allen Cymerman, Stephen R. Muza, Charles S. Fulco, Arthur E. Weyman, Paul B. Rock, Kibar Yared, and N. Stuart Harris
- Subjects
Adult ,Male ,medicine.medical_specialty ,Physiology ,Moderate altitude ,Pulmonary arterial pressure ,Altitude Sickness ,Pulmonary Artery ,Young Adult ,Altitude ,Oxygen Consumption ,Reference Values ,Internal medicine ,medicine ,Humans ,Sea level ,Arterial hemodynamics ,business.industry ,Pulmonary Gas Exchange ,Public Health, Environmental and Occupational Health ,Hemodynamics ,General Medicine ,Effects of high altitude on humans ,medicine.disease ,Environment, Controlled ,Pulmonary hypertension ,Adaptation, Physiological ,Nontherapeutic Human Experimentation ,Surgery ,Mountaineering ,Pulmonary Alveoli ,Hypobaric chamber ,Cardiology ,business - Abstract
Staged ascent (SA), temporary residence at moderate altitude en route to high altitude, reduces the incidence and severity of noncardiopulmonary altitude illness such as acute mountain sickness. To date, the impact of SA on pulmonary arterial pressure (PAP) is unknown. We tested the hypothesis that SA would attenuate the PAP increase that occurs during rapid, direct ascent (DA). Transthoracic echocardiography was used to estimate mean PAP in 10 healthy males at sea level (SL, P(B) approximately 760 torr), after DA to simulated high altitude (hypobaric chamber, P(B) approximately 460 torr), and at 2 times points (90 min and 4 days) during exposure to terrestrial high altitude (P(B) approximately 460 torr) after SA (7 days, moderate altitude, P(B) approximately 548 torr). Alveolar oxygen pressure (Pao(2)) and arterial oxygenation saturation (Sao(2)) were measured at each time point. Compared to mean PAP at SL (mean +/- SD, 14 +/- 3 mmHg), mean PAP increased after DA to 37 +/- 8 mmHg (Delta = 24 +/- 10 mmHg, p0.001) and was negatively correlated with both Pao(2) (r(2) = 0.57, p = 0.011) and Sao(2) (r(2) = 0.64, p = 0.005). In comparison, estimated mean PAP after SA increased to only 25 +/- 4 mmHg (Delta = 11 +/- 6 mmHg, p0.001), remained unchanged after 4 days of high altitude residence (24 +/- 5 mmHg, p = not significant, or NS), and did not correlate with either parameter of oxygenation. SA significantly attenuated the PAP increase associated with continuous direct ascent to high altitude and appeared to uncouple PAP from both alveolar hypoxia and arterial hypoxemia.
- Published
- 2010
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