2024
The metabolic and physiologic impairments underlying long COVID associated exercise intolerance
Leitner B, Joseph P, Quast A, Ramirez M, Heerdt P, Villalobos J, Singh I. The metabolic and physiologic impairments underlying long COVID associated exercise intolerance. Pulmonary Circulation 2024, 14: e70009. PMID: 39544193, PMCID: PMC11560803, DOI: 10.1002/pul2.70009.Peer-Reviewed Original ResearchPeak VO<sub>2</sub>Long COVID patientsCOVID patientsReduced peak VOSeverity of SARS-CoV-2 infectionSystemic oxygen extractionSARS-CoV-2 infectionLong COVIDArterial blood samplesQuantitative metabolomicsPeak VOVenous lactateCardiac outputImpaired mitochondrial ATP productionMild infectionExercise capacityPatientsMitochondrial ATP productionExercise intoleranceArteriovenous gradientBlood samplesOxygen extractionDependent mannerMetabolomicsPhysiological impairmentRight Ventricular Pressure Waveform Analysis—Clinical Relevance and Future Directions
Heerdt P, Kheyfets V, Oakland H, Joseph P, Singh I. Right Ventricular Pressure Waveform Analysis—Clinical Relevance and Future Directions. Journal Of Cardiothoracic And Vascular Anesthesia 2024, 38: 2433-2445. PMID: 39025682, DOI: 10.1053/j.jvca.2024.06.022.Peer-Reviewed Original ResearchRight ventricular pressureRight ventricular functionVentricular pressureVentricular functionMeasuring right ventricular pressureMeasurements of right ventricular pressurePeak right ventricular pressurePulmonary artery pressureEvaluate cardiac functionPulmonary arteryStroke volume measurementsRight atriumCardiac functionDiastolic fillingSurgical patientsArterial pressureClinical valueDemonstrating utilityVolume measurementsMeasurements of pressurePressure waveformAccurate surrogateContinuous measurement of pressurePhysiological factorsEchocardiographyThree-dimensional (3D) Right Ventricular Surface Strain Computed From 3D Echocardiography Correlates With RVEF and Reveals Differences in Deformation Based on Severity of Pulmonary Arterial Hypertension Symptoms
Oakland H, Bellumkonda L, Sugeng L, Joseph P, Izzi D, Zalik F, McCabe S, Raza A, Amendola R, Heerdt P, Singh I, Hunter K. Three-dimensional (3D) Right Ventricular Surface Strain Computed From 3D Echocardiography Correlates With RVEF and Reveals Differences in Deformation Based on Severity of Pulmonary Arterial Hypertension Symptoms. 2024, a7381-a7381. DOI: 10.1164/ajrccm-conference.2024.209.1_meetingabstracts.a7381.Peer-Reviewed Original Research
2023
Differential cardiopulmonary haemodynamic phenotypes in PASC-related exercise intolerance
Kahn P, Joseph P, Heerdt P, Singh I. Differential cardiopulmonary haemodynamic phenotypes in PASC-related exercise intolerance. ERJ Open Research 2023, 10: 00714-2023. PMID: 38348243, PMCID: PMC10860209, DOI: 10.1183/23120541.00714-2023.Peer-Reviewed Original ResearchInvasive cardiopulmonary exercise testingRight heart catheterizationPASC patientsExertional intoleranceCardiac outputPulmonary artery wedge pressurePeak VO 2Supranormal cardiac outputPeak exercise capacityCardiopulmonary exercise testingMaximal voluntary ventilationPost-acute sequelaeBody mass indexSystemic oxygen extractionMild acute illnessSARS-CoV-2Exercise hemodynamicsHFpEF patientsHFpEF phenotypeHeart catheterizationWedge pressureAcute illnessExercise capacityExercise testingHemodynamic abnormalitiesPost-Acute Sequelae of SARS-CoV-2 More Than Deconditioning
Joseph P, Singh I. Post-Acute Sequelae of SARS-CoV-2 More Than Deconditioning. CHEST Journal 2023, 164: 583-584. PMID: 37689472, DOI: 10.1016/j.chest.2023.03.014.Peer-Reviewed Original ResearchIntegrating Right Ventricular Pressure Waveform Analysis With Two-Point Volume Measurement for Quantification of Systolic and Diastolic Function: Experimental Validation and Clinical Application
Heerdt P, Martin-Flores M, Oakland H, Joseph P, Singh I. Integrating Right Ventricular Pressure Waveform Analysis With Two-Point Volume Measurement for Quantification of Systolic and Diastolic Function: Experimental Validation and Clinical Application. Journal Of Cardiothoracic And Vascular Anesthesia 2023, 37: 1929-1937. PMID: 37422337, PMCID: PMC10529383, DOI: 10.1053/j.jvca.2023.06.011.Peer-Reviewed Original ResearchConceptsRight heart catheterizationHeart catheterizationDiastolic functionRV volumesBeat measuresDiagnostic right heart catheterizationReference standardRight ventricular contractilityEnd-diastolic pressurePressure waveform analysisEnd-systolic elastancePotential clinical utilityClinical applicationRV volume measurementsVolume measurementsRV contractilityRV systolicVentricular contractilityRV pressureBland-Altman analysisClinical utilityAnesthetized swineNitric oxideExperimental modelContractilitySex Differences in Hemodynamic Response to Exercise in Patients With Myalgic Encephalomyelitis: Insights From Invasive Cardiopulmonary Exercise Testing
Wichmann Madsen K, Squires J, Stovall M, Al-Zayer S, Chang C, Xiao W, Pari R, Joseph P, Systrom D. Sex Differences in Hemodynamic Response to Exercise in Patients With Myalgic Encephalomyelitis: Insights From Invasive Cardiopulmonary Exercise Testing. 2023, a2995-a2995. DOI: 10.1164/ajrccm-conference.2023.207.1_meetingabstracts.a2995.Peer-Reviewed Original ResearchProteomic profiling demonstrates inflammatory and endotheliopathy signatures associated with impaired cardiopulmonary exercise hemodynamic profile in Post Acute Sequelae of SARS‐CoV‐2 infection (PASC) syndrome
Singh I, Leitner B, Wang Y, Zhang H, Joseph P, Lutchmansingh D, Gulati M, Possick J, Damsky W, Hwa J, Heerdt P, Chun H. Proteomic profiling demonstrates inflammatory and endotheliopathy signatures associated with impaired cardiopulmonary exercise hemodynamic profile in Post Acute Sequelae of SARS‐CoV‐2 infection (PASC) syndrome. Pulmonary Circulation 2023, 13: e12220. PMID: 37091121, PMCID: PMC10113513, DOI: 10.1002/pul2.12220.Peer-Reviewed Original ResearchInvasive cardiopulmonary exercise testPASC patientsPost-acute sequelaeAcute sequelaeInfection syndromeUnexplained exertional intoleranceCardiopulmonary exercise testSystemic oxygen deliveryPersistent inflammatory stateVenous blood plasmaExertional intolerancePeak exerciseEndothelial dysfunctionHemodynamic profileInflammatory stateExercise testFibrotic processPathophysiological hallmarkAberrant protein expressionExpression of proteinsOxygen deliveryOxygen extractionProteomic profilingPatientsPhysiologic responsesExercise Pathophysiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Postacute Sequelae of SARS-CoV-2 More in Common Than Not?
Joseph P, Singh I, Oliveira R, Capone C, Mullen M, Cook D, Stovall M, Squires J, Madsen K, Waxman A, Systrom D. Exercise Pathophysiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Postacute Sequelae of SARS-CoV-2 More in Common Than Not? CHEST Journal 2023, 164: 717-726. PMID: 37054777, PMCID: PMC10088277, DOI: 10.1016/j.chest.2023.03.049.Peer-Reviewed Original ResearchConceptsMyalgic encephalomyelitis/chronic fatigue syndromeME/CFSChronic fatigue syndromeSARS-CoV-2Fatigue syndromePostacute sequelaeCardiopulmonary exercise testingSystemic blood flowExercise pathophysiologyExertional intoleranceIntractable fatigueExercise testingAcute infectionPostexertional malaiseExercise intoleranceOrthostatic intoleranceVentilatory controlLong-term consequencesBlood flowClinical overlapSuch symptomsIntoleranceSequelaeCOVID-19SyndromeResponse to letter to the editor “noninvasive determinants of pulmonary hypertension in interstitial lung disease”
Joseph P, Savarimuthu S, Oakland H, Cullinan M, Heerdt P, Singh I. Response to letter to the editor “noninvasive determinants of pulmonary hypertension in interstitial lung disease”. Pulmonary Circulation 2023, 13: e12238. PMID: 37180828, PMCID: PMC10166920, DOI: 10.1002/pul2.12238.Peer-Reviewed Original ResearchNoninvasive determinants of pulmonary hypertension in interstitial lung disease
Joseph P, Savarimuthu S, Zhao J, Yan X, Oakland H, Cullinan M, Heerdt P, Singh I. Noninvasive determinants of pulmonary hypertension in interstitial lung disease. Pulmonary Circulation 2023, 13: e12197. PMID: 36814586, PMCID: PMC9939578, DOI: 10.1002/pul2.12197.Peer-Reviewed Original ResearchInterstitial lung diseaseFVC/DLCO ratioPH-ILDRight heart catheterizationPulmonary hypertensionHeart catheterizationILD patientsLung diseaseDiagnostic right heart catheterizationRight ventricular systolic pressurePulmonary vascular capacitanceVentricular systolic pressureCharacteristic curve analysisMaximum oxygen uptakeExertional capacityNoninvasive determinantsSystolic pressureVascular capacitancePhysiologic evaluationPatientsNoninvasive variablesMultivariate analysisMmHgDiagnostic standardPotential initiation
2022
Short- and long-term noninvasive cardiopulmonary exercise assessment in previously hospitalised COVID-19 patients
Singh I, Joseph P. Short- and long-term noninvasive cardiopulmonary exercise assessment in previously hospitalised COVID-19 patients. European Respiratory Journal 2022, 61: 2201739. PMID: 36137592, PMCID: PMC9515479, DOI: 10.1183/13993003.01739-2022.Peer-Reviewed Original ResearchConceptsCOVID-19 patientsAcute respiratory syndrome coronavirus 2 infectionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectionNoninvasive cardiopulmonary exercise testingSyndrome coronavirus 2 infectionCoronavirus 2 infectionCardiopulmonary exercise testingCoronavirus disease 2019 (COVID-19) pandemicSARS-CoV-2Disease 2019 pandemicExercise testingGlobal healthcare systemsInterval improvementExercise assessmentAerobic capacityHealthcare systemPatientsHospitalisationWorld populationPopulationInfectionMonthsNeurovascular Dysregulation and Acute Exercise Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome A Randomized, Placebo-Controlled Trial of Pyridostigmine
Joseph P, Pari R, Miller S, Warren A, Stovall MC, Squires J, Chang CJ, Xiao W, Waxman AB, Systrom DM. Neurovascular Dysregulation and Acute Exercise Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome A Randomized, Placebo-Controlled Trial of Pyridostigmine. CHEST Journal 2022, 162: 1116-1126. PMID: 35526605, DOI: 10.1016/j.chest.2022.04.146.Peer-Reviewed Original ResearchConceptsME/CFSInvasive cardiopulmonary exercise testRight atrial pressureCardiac outputNeurovascular dysregulationAtrial pressurePostexertional malaiseExercise intoleranceMyalgic encephalomyelitis/chronic fatigue syndromePeak exercise oxygen uptakeRight ventricular filling pressuresEnd pointPlacebo-controlled trialPrimary end pointSecondary end pointsVentricular filling pressureCardiopulmonary exercise testChronic fatigue syndromeExercise oxygen uptakeA RandomizedIntractable fatigueOral pyridostigminePyridostigmine groupExercise capacitySystemic hemodynamicsAcute Effect of Pyridostigmine in Exertional Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Randomized Placebo-Controlled Clinical Trial
Stovall M, Joseph P, Pari R, Warren A, Miller S, Squires J, Xiao W, Waxman A, Systrom D. Acute Effect of Pyridostigmine in Exertional Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Randomized Placebo-Controlled Clinical Trial. 2022, a2063-a2063. DOI: 10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a2063.Peer-Reviewed Original ResearchReply to Grignola and Trujillo
Oakland HT, Joseph P, Naeije R, Elassal A, Cullinan M, Heerdt PM, Singh I. Reply to Grignola and Trujillo. Journal Of Applied Physiology 2022, 132: 219-219. PMID: 35030044, PMCID: PMC8759952, DOI: 10.1152/japplphysiol.00810.2021.Commentaries, Editorials and LettersCardiopulmonary Exercise Testing in Pulmonary Vascular Disease
Joseph P, Systrom D. Cardiopulmonary Exercise Testing in Pulmonary Vascular Disease. 2022, 582-596. DOI: 10.1016/b978-0-12-801238-3.11478-3.ChaptersInvasive cardiopulmonary exercise testingCardiopulmonary exercise testingPulmonary vascular diseaseArtery catheterExercise testingCardiac outputPulmonary circulationVascular diseaseNoninvasive cardiopulmonary exercise testingNormal diagnostic workupPulmonary parenchymal diseaseRight heart catheterizationPulmonary arterial hypertensionPulmonary artery catheterArterial blood gasesRadial artery catheterModern medical therapyUseful screening testFick cardiac outputMeasurements of rightArterial hypertensionHeart catheterizationPulmonary hypertensionVenous hypertensionExercise impairment
2021
Sex Differences and the Role of Sex Hormones in Pulmonary Hypertension
Oakland HT, Joseph P. Sex Differences and the Role of Sex Hormones in Pulmonary Hypertension. Clinics In Chest Medicine 2021, 42: 457-465. PMID: 34353451, DOI: 10.1016/j.ccm.2021.04.006.ChaptersConceptsPulmonary hypertensionProgressive pulmonary vascular remodelingRight heart failurePulmonary arterial hypertensionPulmonary vascular remodelingSex differencesArterial hypertensionHeart failureFemale sexSex hormonesVascular remodelingHypertensionFuture treatmentBeneficial effectsEventual developmentMultiple mechanismsVasoconstrictionEarlier descriptionsInflammationPathophysiologyEstrogenPrevalenceDiseaseHormonePersistent Exertional Intolerance After COVID-19 Insights From Invasive Cardiopulmonary Exercise Testing
Singh I, Joseph P, Heerdt PM, Cullinan M, Lutchmansingh DD, Gulati M, Possick JD, Systrom DM, Waxman AB. Persistent Exertional Intolerance After COVID-19 Insights From Invasive Cardiopulmonary Exercise Testing. CHEST Journal 2021, 161: 54-63. PMID: 34389297, PMCID: PMC8354807, DOI: 10.1016/j.chest.2021.08.010.Peer-Reviewed Original ResearchConceptsInvasive cardiopulmonary exercise testingCardiopulmonary exercise testingCardiopulmonary diseaseExercise testingControl participantsPeak VOExertional limitationCOVID-19Greater ventilatory inefficiencyPeak cardiac indexSex-matched control participantsCohort of patientsSystemic oxygen extractionDead space ventilationOnly mild symptomsExertional intoleranceCardiac indexPulmonary hemodynamicsAcute infectionVentilatory inefficiencyExercise intolerancePathophysiologic mechanismsMild symptomsHyperventilatory responseOxygen extractionArterial load and right ventricular-vascular coupling in pulmonary hypertension
Oakland H, Joseph P, Naeije R, Elassal A, Cullinan M, Heerdt PM, Singh I. Arterial load and right ventricular-vascular coupling in pulmonary hypertension. Journal Of Applied Physiology 2021, 131: 424-433. PMID: 34043473, PMCID: PMC8325619, DOI: 10.1152/japplphysiol.00204.2021.Peer-Reviewed Original ResearchConceptsPulmonary artery hypertensionRV-PA uncouplingPulmonary vascular resistancePressure waveform analysisRight ventriclePulmonary vascular impedancePulmonary hypertensionVascular impedanceRight heart catheterization dataRight ventricular-vascular couplingRV-pulmonary arterial couplingCpc-PH groupEjection fraction patientsHeart catheterization dataRV pressure curveRV-PA couplingLeft heart diseaseVentricular-vascular couplingSex-matched controlsAfterload parametersCpc-PHIpc-PHPH-HFpEFRV afterloadArtery hypertensionInsights From Invasive Cardiopulmonary Exercise Testing of Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Joseph P, Arevalo C, Oliveira RKF, Faria-Urbina M, Felsenstein D, Oaklander AL, Systrom DM. Insights From Invasive Cardiopulmonary Exercise Testing of Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. CHEST Journal 2021, 160: 642-651. PMID: 33577778, PMCID: PMC8727854, DOI: 10.1016/j.chest.2021.01.082.Peer-Reviewed Original ResearchConceptsSmall fiber neuropathyRight atrial pressurePostural orthostatic tachycardiaMyalgic encephalomyelitis/chronic fatigue syndromeCardiopulmonary exercise testingChronic fatigue syndromeExertional intoleranceExercise testingFatigue syndromeControl subjectsOxygen extractionInvasive cardiopulmonary exercise testingLow right atrial pressureME/CFS criteriaHigh pulmonary blood flowME/CFS patientsPeripheral oxygen extractionSmall fiber pathologyPulmonary blood flowSystemic oxygen extractionCardiac returnIntrinsic heartNeurovascular dysregulationRight shuntingCFS patients