2023
A Case of Fulminant Right Heart Failure Owing to Tumoral Pulmonary Hypertension
Wang K, Verma A, Fish K, Hu J, Miller P, Morrow J, Singh I, Young L. A Case of Fulminant Right Heart Failure Owing to Tumoral Pulmonary Hypertension. JACC Case Reports 2023, 10: 101715. PMID: 36974052, PMCID: PMC10039392, DOI: 10.1016/j.jaccas.2022.101715.Peer-Reviewed Case Reports and Technical Notes
2022
122-LB: Effect of Dapagliflozin on Mitochondrial Metabolism and Cardiac Function in the Failing Heart
GOEDEKE L, MA Y, ZHANG J, GUERRERA N, WU X, ZHANG D, KAHN M, ZHANG X, YOUNG L, SHULMAN G. 122-LB: Effect of Dapagliflozin on Mitochondrial Metabolism and Cardiac Function in the Failing Heart. Diabetes 2022, 71 DOI: 10.2337/db22-122-lb.Peer-Reviewed Original ResearchDAPA treatmentLV ejection fractionEjection fractionHeart failureMI ratsCardiac outputMyocardial infarctionCardiac functionLeft ventricularEffect of dapagliflozinMale Sprague-DawleyPlasma glucose concentrationMalonyl-CoA contentMitochondrial oxidationKetone availabilityΒOHB levelsVehicle treatmentPermanent ligationSGLT2 inhibitionSGLT2 inhibitorsCardioprotective effectsCoronary arteryAcetyl-CoA contentFailing HeartMitochondrial metabolismMuscle LIM Protein Force-Sensing Mediates Sarcomeric Biomechanical Signaling in Human Familial Hypertrophic Cardiomyopathy
Riaz M, Park J, Sewanan LR, Ren Y, Schwan J, Das SK, Pomianowski PT, Huang Y, Ellis MW, Luo J, Liu J, Song L, Chen IP, Qiu C, Yazawa M, Tellides G, Hwa J, Young LH, Yang L, Marboe CC, Jacoby DL, Campbell SG, Qyang Y. Muscle LIM Protein Force-Sensing Mediates Sarcomeric Biomechanical Signaling in Human Familial Hypertrophic Cardiomyopathy. Circulation 2022, 145: 1238-1253. PMID: 35384713, PMCID: PMC9109819, DOI: 10.1161/circulationaha.121.056265.Peer-Reviewed Original ResearchConceptsHypertrophic cardiomyopathySarcomeric mutationsFamilial hypertrophic cardiomyopathySudden cardiac deathCardiac myosin heavy chainMechanism-based treatmentsDevelopment of hypertrophyActivated T cellsCalcineurin-nuclear factorForce productionPhenotypic expressionPluripotent stem cell-derived cardiomyocytesStem cell-derived cardiomyocytesHeart failureCardiac deathVentricular hypertrophyCell-derived cardiomyocytesCardiac contractilityPharmacological interventionsT cellsCardiac diseaseCardiac hypertrophyPatient-specific induced pluripotent stem cellsPharmacological meansTwitch relaxationEfficacy of lower doses of pioglitazone after stroke or transient ischaemic attack in patients with insulin resistance
Spence JD, Viscoli C, Kernan WN, Young LH, Furie K, DeFronzo R, Abdul‐Ghani M, Dandona P, Inzucchi SE. Efficacy of lower doses of pioglitazone after stroke or transient ischaemic attack in patients with insulin resistance. Diabetes Obesity And Metabolism 2022, 24: 1150-1158. PMID: 35253334, DOI: 10.1111/dom.14687.Peer-Reviewed Original ResearchConceptsNew-onset diabetesAdjusted hazard ratioHazard ratioLow dosesAdverse effectsInsulin Resistance InterventionTransient ischemic attackSecondary prevention strategiesAnti-atherosclerotic propertiesInsulin-sensitizing drugsLess adverse effectsIschemic attackStudy drugHeart failureStroke trialsAdverse outcomesInsulin resistancePioglitazonePrevention strategiesHigh dosesResistance InterventionFull doseWeight gainDiabetesPatients
2021
323-OR: SGLT2 Inhibition Promotes Myocardial Ketone Utilization in the Normal and Failing Heart
GOEDEKE L, LEE J, MA Y, HU X, ZHANG J, DONG J, GALSGAARD K, GUERRERA N, HAEDERSDAL S, ZHANG X, PERRY R, CLINE G, YOUNG L, SHULMAN G. 323-OR: SGLT2 Inhibition Promotes Myocardial Ketone Utilization in the Normal and Failing Heart. Diabetes 2021, 70 DOI: 10.2337/db21-323-or.Peer-Reviewed Original ResearchPlasma glucose concentrationDAPA treatmentHeart failureAwake male Sprague-Dawley ratsMajor adverse cardiovascular eventsMale Sprague-Dawley ratsRecent clinical outcome studiesAdverse cardiovascular eventsHeart failure ratsType 2 diabetesClinical outcome studiesSprague-Dawley ratsGlucose concentrationΒOHB levelsCardiovascular eventsCardiovascular benefitsVehicle treatmentPermanent ligationSGLT2 inhibitorsCoronary arteryControl ratsKetone utilizationDawley ratsAcute effectsFailing Heart
2019
Cardiomyocyte d-dopachrome tautomerase protects against heart failure
Ma Y, Su KN, Pfau D, Rao VS, Wu X, Hu X, Leng L, Du X, Piecychna M, Bedi K, Campbell SG, Eichmann A, Testani JM, Margulies KB, Bucala R, Young LH. Cardiomyocyte d-dopachrome tautomerase protects against heart failure. JCI Insight 2019, 4: e128900. PMID: 31484822, PMCID: PMC6777911, DOI: 10.1172/jci.insight.128900.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalciumCardiomegalyCytokinesDisease Models, AnimalEchocardiographyGene DeletionGene ExpressionGenetic Predisposition to DiseaseHeart FailureHumansIntramolecular OxidoreductasesMaleMAP Kinase Kinase KinasesMiceMice, Inbred C57BLMice, KnockoutMyocytes, CardiacRecombinant ProteinsSignal TransductionTranscriptomeVascular Endothelial Growth Factor AConceptsTransverse aortic constrictionHeart failureRecombinant DDTConnective tissue growth factor expressionTissue growth factor expressionMore interstitial fibrosisAdvanced heart failureCardiac pressure overloadExperimental heart failureCardiac contractile dysfunctionLittermate control miceSmad-2 activationGrowth factor expressionSarcoplasmic reticulum calcium ATPaseMacrophage migration inhibitory factor (MIF) familyReticulum calcium ATPasePulmonary edemaCardiac dilatationContractile dysfunctionControl miceInterstitial fibrosisPressure overloadAntifibrotic actionAortic constrictionLow VEGFPioglitazone Therapy in Patients With Stroke and Prediabetes
Spence JD, Viscoli CM, Inzucchi SE, Dearborn-Tomazos J, Ford GA, Gorman M, Furie KL, Lovejoy AM, Young LH, Kernan WN. Pioglitazone Therapy in Patients With Stroke and Prediabetes. JAMA Neurology 2019, 76: 526-535. PMID: 30734043, PMCID: PMC6515584, DOI: 10.1001/jamaneurol.2019.0079.Peer-Reviewed Original ResearchMeSH KeywordsAcute Coronary SyndromeAgedDiabetes Mellitus, Type 2Disease ProgressionFemaleGlycated HemoglobinHeart FailureHospitalizationHumansHypoglycemic AgentsInsulin ResistanceMaleMedication AdherenceMiddle AgedMyocardial InfarctionPioglitazonePrediabetic StateProportional Hazards ModelsRecurrenceSecondary PreventionStrokeConceptsAcute coronary syndromeStroke/myocardial infarctionTransient ischemic attackMyocardial infarctionCoronary syndromeHeart failureIRIS trialInsulin resistanceGood adherenceIschemic attackRecurrent strokeHazard ratioClinical trialsStroke/transient ischemic attackRandomized multicenter clinical trialAmerican Diabetes Association criteriaInsulin Resistance InterventionHemoglobin A1c levelsEffect of pioglitazoneInsulin-sensitizing agentsMulticenter clinical trialPlasma glucose levelsSerious bone fracturesPlacebo cohortPrior strokeAngiotensin Receptor Neprilysin Inhibitor Attenuates Myocardial Remodeling and Improves Infarct Perfusion in Experimental Heart Failure
Pfau D, Thorn SL, Zhang J, Mikush N, Renaud JM, Klein R, deKemp RA, Wu X, Hu X, Sinusas AJ, Young LH, Tirziu D. Angiotensin Receptor Neprilysin Inhibitor Attenuates Myocardial Remodeling and Improves Infarct Perfusion in Experimental Heart Failure. Scientific Reports 2019, 9: 5791. PMID: 30962467, PMCID: PMC6453892, DOI: 10.1038/s41598-019-42113-0.Peer-Reviewed Original ResearchMeSH KeywordsAminobutyratesAngiotensin Receptor AntagonistsAnimalsBiphenyl CompoundsDrug CombinationsHeartHeart FailureMaleMyocardial Reperfusion InjuryMyocardiumNeovascularization, PhysiologicNeprilysinOrganotechnetium CompoundsPeptides, CyclicRatsRats, Inbred LewSingle Photon Emission Computed Tomography Computed TomographyTetrazolesValsartanVascular Endothelial Growth Factor AVentricular RemodelingConceptsSacubitril/valsartanExperimental heart failureHeart failureMyocardial infarctionMyocardial remodelingAngiotensin receptor neprilysin inhibitorAngiotensin receptor blocker valsartanMicroSPECT/CT imagingReceptor blocker valsartanHeart failure patientsProgressive LV dilationGlobal LV functionLV contractile dysfunctionNeprilysin inhibitor sacubitrilBorder zoneLimited remodelingFailure patientsInhibitor therapyMale LewisWeeks treatmentLV dilationLV functionNeprilysin inhibitorContractile dysfunctionInterstitial fibrosis
2018
Heart Failure After Ischemic Stroke or Transient Ischemic Attack in Insulin-Resistant Patients Without Diabetes Mellitus Treated With Pioglitazone
Young LH, Viscoli CM, Schwartz GG, Inzucchi SE, Curtis JP, Gorman MJ, Furie KL, Conwit R, Spatz E, Lovejoy A, Abbott JD, Jacoby DL, Kolansky DM, Ling FS, Pfau SE, Kernan WN. Heart Failure After Ischemic Stroke or Transient Ischemic Attack in Insulin-Resistant Patients Without Diabetes Mellitus Treated With Pioglitazone. Circulation 2018, 138: 1210-1220. PMID: 29934374, PMCID: PMC6202153, DOI: 10.1161/circulationaha.118.034763.Peer-Reviewed Original ResearchConceptsRisk of HFTransient ischemic attackEffect of pioglitazoneHF riskHeart failureInsulin-resistant patientsMyocardial infarctionIschemic attackCardiovascular benefitsIschemic strokeDiabetes mellitusInsulin resistanceHigher C-reactive proteinComposite of strokeHF risk scoreHigher HF riskDrug dose reductionHospitalized heart failureIncident myocardial infarctionLower mean doseC-reactive proteinBaseline patient featuresHF hospitalizationCardiovascular eventsPlacebo group
2013
Bevacizumab: Finding its niche in the treatment of heart failure secondary to liver vascular malformations in hereditary hemorrhagic telangiectasia
Young LH, Henderson KJ, White RI, Garcia‐Tsao G. Bevacizumab: Finding its niche in the treatment of heart failure secondary to liver vascular malformations in hereditary hemorrhagic telangiectasia. Hepatology 2013, 58: 442-445. PMID: 23686865, DOI: 10.1002/hep.26472.Commentaries, Editorials and Letters
2006
Diabetes Mellitus and Cardiovascular Disease
Chyun DA, Young LH. Diabetes Mellitus and Cardiovascular Disease. Nursing Clinics Of North America 2006, 41: 681-695. PMID: 17059982, DOI: 10.1016/j.cnur.2006.07.007.BooksConceptsCoronary heart diseaseCardiovascular diseaseHeart diseasePeripheral vascular diseaseAcute myocardial infarctionMultiple risk factorsComplex pathophysiologic processHeart failureChronic manifestationsMyocardial infarctionVascular diseaseRisk factorsPathophysiologic processesSudden deathHigh riskType 1DiseaseEarly detectionDiabetesHypertensionMellitusInfarctionStrokeIndividualsPrevention
2005
AMP-Activated Protein Kinase: A Key Stress Signaling Pathway in the Heart
Young LH, Li J, Baron SJ, Russell RR. AMP-Activated Protein Kinase: A Key Stress Signaling Pathway in the Heart. Trends In Cardiovascular Medicine 2005, 15: 110-118. PMID: 16039971, DOI: 10.1016/j.tcm.2005.04.005.BooksConceptsLeft ventricular contractile dysfunctionVentricular contractile dysfunctionFatty acid oxidationProtein kinaseCardiovascular actionsHeart failureContractile dysfunctionWolff-ParkinsonWhite syndromeTransgenic miceGlycogen overloadStress Signaling PathwaysImportant regulatory mechanismSignaling pathwaysHeartAcid oxidationGlucose transportMolecular mechanismsAnabolic pathwaysRegulatory mechanismsAMPHeart Failure and Cardiac Dysfunction in Diabetes
Young L, Russell R, Chyun D. Heart Failure and Cardiac Dysfunction in Diabetes. Contemporary Cardiology 2005, 555-578. DOI: 10.1385/1-59259-908-7:555.Peer-Reviewed Original ResearchType 2 diabetesHeart failureHigh cardiovascular morbidityPresence of diabetesOral hypoglycemic agentsAge-adjusted riskImpact of diabetesFramingham Heart StudyNondiabetic patientsCardiovascular morbidityNondiabetic menPatient yearsOlder patientsSuch patientsCardiac dysfunctionHypoglycemic agentsHeart StudyClinical problemPatientsDiabetesType 1IncidenceRiskFailureMorbidity
2004
AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury
Russell RR, Li J, Coven DL, Pypaert M, Zechner C, Palmeri M, Giordano FJ, Mu J, Birnbaum MJ, Young LH. AMP-activated protein kinase mediates ischemic glucose uptake and prevents postischemic cardiac dysfunction, apoptosis, and injury. Journal Of Clinical Investigation 2004, 114: 495-503. PMID: 15314686, PMCID: PMC503766, DOI: 10.1172/jci19297.Peer-Reviewed Original ResearchConceptsLow-flow ischemiaGlucose uptakePostischemic reperfusionWT heartsLeft ventricular dPNormal fractional shorteningLV contractile functionPostischemic cardiac dysfunctionInsulin-stimulated glucose uptakeImportant protective roleLong-term inhibitionFatty acid oxidationFractional shorteningHeart failureVentricular dPCardiac consequencesCardiac dysfunctionCaspase-3 activityMyocardial ischemiaContractile functionReperfusionCardiac hypertrophyIschemiaTransgenic miceProtective role
2002
Cardiac outcomes after myocardial infarction in elderly patients with diabetes mellitus.
Chyun D, Vaccarino V, Murillo J, Young LH, Krumholz HM. Cardiac outcomes after myocardial infarction in elderly patients with diabetes mellitus. American Journal Of Critical Care 2002, 11: 504-19. PMID: 12425401, DOI: 10.4037/ajcc2002.11.6.504.Peer-Reviewed Original ResearchConceptsRecurrent myocardial infarctionInsulin-treated diabetes mellitusDiabetes mellitusMyocardial infarctionElderly patientsHeart failureVentricular functionComorbid conditionsClinical findingsIndex myocardial infarctionPoor ventricular functionInsulin-treated diabetesAcute myocardial infarctionCardiac outcomesPoor outcomeMedical recordsMellitusInfarctionMedicare beneficiariesPatientsGreater riskInsulinMortalityRiskOutcomesAcute myocardial infarction in the elderly with diabetes
Chyun D, Vaccarino V, Murillo J, Young LH, Krumholz HM. Acute myocardial infarction in the elderly with diabetes. Heart & Lung 2002, 31: 327-339. PMID: 12487011, DOI: 10.1067/mhl.2002.126049.Peer-Reviewed Original ResearchConceptsAcute myocardial infarctionDiabetes mellitusMyocardial infarctionHeart failureComorbid conditionsMortality rateNon-Q-wave myocardial infarctionHistory of DMInsulin-treated diabetes mellitusRetrospective medical record reviewHigher body mass indexAcute MI settingPoor functional statusBlood pressure managementMedical record reviewSpecific comorbid conditionsSecondary preventive interventionsBody mass indexShort-term mortalityCooperative Cardiovascular ProjectEntire Medicare populationShort-term riskAggressive lipidDM statusChest pain
2000
Liver Disease in Patients with Hereditary Hemorrhagic Telangiectasia
Garcia-Tsao G, Korzenik J, Young L, Henderson K, Jain D, Byrd B, Pollak J, White R. Liver Disease in Patients with Hereditary Hemorrhagic Telangiectasia. New England Journal Of Medicine 2000, 343: 931-936. PMID: 11006369, DOI: 10.1056/nejm200009283431305.Peer-Reviewed Original ResearchConceptsHereditary hemorrhagic telangiectasiaHigh-output heart failureHemorrhagic telangiectasiaHeart failureMedian periodPortal hypertensionLiver involvementClinical findingsBiliary diseasePulmonary capillary wedge pressureElevated alkaline phosphatase levelsHepatic sinusoidal pressureSymptomatic liver involvementTypical clinical presentationAlkaline phosphatase levelsAutosomal dominant disorderHyperdynamic circulationAngiodysplastic lesionsCardiac indexLiver transplantationVariceal bleedingWedge pressureMedical therapyRendu-OslerClinical presentation