2024
Sacubitril/Valsartan in Patients Hospitalized With Decompensated Heart Failure
Morrow D, Velazquez E, Desai A, DeVore A, Lepage S, Park J, Sharma K, Solomon S, Starling R, Ward J, Williamson K, Zieroth S, Hernandez A, Mentz R, Braunwald E. Sacubitril/Valsartan in Patients Hospitalized With Decompensated Heart Failure. Journal Of The American College Of Cardiology 2024, 83: 1123-1132. PMID: 38508844, DOI: 10.1016/j.jacc.2024.01.027.Peer-Reviewed Original ResearchConceptsWorsening heart failureHeart failureEjection fractionNT-proBNPSpectrum of EFPIONEER-HFSpectrum of left ventricular ejection fractionRandomized trialsTime-averaged proportional changeN-terminal pro-B-type natriuretic peptidePro-B-type natriuretic peptideLeft ventricular ejection fractionWorsening heart failure eventDecompensated heart failureVentricular ejection fractionPlasma NT-proBNPPIONEER-HF trialDouble-blindMedian ageMedian EFSNatriuretic peptideSymptomatic hypotensionBaseline characteristicsClinical outcomesPooled analysis
2023
Angiotensin-Neprilysin Inhibition in Patients With Mildly Reduced or Preserved Ejection Fraction and Worsening Heart Failure
Mentz R, Ward J, Hernandez A, Lepage S, Morrow D, Sarwat S, Sharma K, Starling R, Velazquez E, Williamson K, Desai A, Zieroth S, Solomon S, Braunwald E, Investigators P. Angiotensin-Neprilysin Inhibition in Patients With Mildly Reduced or Preserved Ejection Fraction and Worsening Heart Failure. Journal Of The American College Of Cardiology 2023, 82: 1-12. PMID: 37212758, DOI: 10.1016/j.jacc.2023.04.019.Peer-Reviewed Original ResearchConceptsSacubitril/valsartanEjection fractionWHF eventNT-proBNPSymptomatic hypotensionHeart failureAmino-terminal pro-B-type natriuretic peptideTerminal pro-B-type natriuretic peptidePro-B-type natriuretic peptidePlasma NT-proBNP levelsAngiotensin-Neprilysin InhibitionNT-proBNP changesNT-proBNP levelsUrgent HF visitsChronic heart failureHeart failure eventsLarge treatment effectsHF hospitalizationHF visitsCardiovascular deathPrimary endpointRenal functionClinical benefitNatriuretic peptideWeek 4Sacubitril/valsartan in heart failure with mildly reduced or preserved ejection fraction: a pre-specified participant-level pooled analysis of PARAGLIDE-HF and PARAGON-HF
Vaduganathan M, Mentz R, Claggett B, Miao Z, Kulac I, Ward J, Hernandez A, Morrow D, Starling R, Velazquez E, Williamson K, Desai A, Zieroth S, Lefkowitz M, McMurray J, Braunwald E, Solomon S. Sacubitril/valsartan in heart failure with mildly reduced or preserved ejection fraction: a pre-specified participant-level pooled analysis of PARAGLIDE-HF and PARAGON-HF. European Heart Journal 2023, 44: 2982-2993. PMID: 37210743, PMCID: PMC10424880, DOI: 10.1093/eurheartj/ehad344.Peer-Reviewed Original ResearchConceptsSacubitril/valsartanRenal composite endpointPARAGON-HFHeart failureEjection fractionPooled analysisHF eventsRenal eventsCardiovascular deathComposite endpointLeft ventricular ejection fractionVentricular ejection fractionActive-controlled trialParticipant-level dataPrimary endpointSecondary endpointsClinical outcomesNatriuretic peptideLike patientsTreatment benefitCare settingsPatientsPrimary analysisLVEFValsartanRationale, Design and Baseline Characteristics of the PARAGLIDE-HF Trial: Sacubitril/Valsartan vs Valsartan in HFmrEF and HFpEF With a Worsening Heart Failure Event
Mentz R, Ward J, Hernandez A, Lepage S, Morrow D, Sarwat S, Sharma K, Solomon S, Starling R, Velazquez E, Williamson K, Zieroth S, Braunwald E. Rationale, Design and Baseline Characteristics of the PARAGLIDE-HF Trial: Sacubitril/Valsartan vs Valsartan in HFmrEF and HFpEF With a Worsening Heart Failure Event. Journal Of Cardiac Failure 2023, 29: 922-930. PMID: 36796671, DOI: 10.1016/j.cardfail.2023.02.001.Peer-Reviewed Original ResearchConceptsSac/ValSacubitril/valsartanHeart failure eventsPARAGON-HF trialWHF eventNT-proBNPEjection fractionHeart failureClinical outcomesAmino-terminal pro-B-type natriuretic peptide levelsTerminal pro-B-type natriuretic peptide levelsB-type natriuretic peptide levelsDe novo HFChronic heart failureNatriuretic peptide levelsPrimary efficacy endpointPg/mLEfficacy endpointSafety endpointSecondary endpointsSymptomatic hypotensionBaseline characteristicsRenal functionStable patientsBlack patients
2020
Initiation of Angiotensin-Neprilysin Inhibition After Acute Decompensated Heart Failure
DeVore AD, Braunwald E, Morrow DA, Duffy CI, Ambrosy AP, Chakraborty H, McCague K, Rocha R, Velazquez EJ. Initiation of Angiotensin-Neprilysin Inhibition After Acute Decompensated Heart Failure. JAMA Cardiology 2020, 5: 202-207. PMID: 31825471, PMCID: PMC6990764, DOI: 10.1001/jamacardio.2019.4665.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAgedAminobutyratesAngiotensin Receptor AntagonistsAngiotensin-Converting Enzyme InhibitorsBiphenyl CompoundsDrug CombinationsEnalaprilFemaleHeart FailureHospitalizationHumansMaleMiddle AgedNatriuretic Peptide, BrainNeprilysinPatient DischargePeptide FragmentsTetrazolesValsartanConceptsAcute decompensated heart failureSacubitril/valsartanNT-proBNP levelsDecompensated heart failureOpen-label studyReduced ejection fractionHospital initiationHeart failurePIONEER-HFEjection fractionWeek 8N-terminal pro-B-type natriuretic peptide levelsPro-B-type natriuretic peptide levelsOpen-label extension phaseAngiotensin-Neprilysin InhibitionHeart failure rehospitalizationPIONEER-HF trialWeek 8 visitNatriuretic peptide levelsActive-controlled trialCardiovascular deathComposite outcomeHemodynamic stabilityRecent hospitalizationClinical outcomes
2019
In‐hospital initiation of sacubitril/valsartan in acute decompensated heart failure: being in the right place at the right time
Ambrosy AP, DeVore AD, Velazquez EJ. In‐hospital initiation of sacubitril/valsartan in acute decompensated heart failure: being in the right place at the right time. European Journal Of Heart Failure 2019, 21: 1008-1011. PMID: 31218805, DOI: 10.1002/ejhf.1540.Peer-Reviewed Original ResearchCardiovascular biomarkers in patients with acute decompensated heart failure randomized to sacubitril-valsartan or enalapril in the PIONEER-HF trial
Morrow DA, Velazquez EJ, DeVore AD, Prescott MF, Duffy CI, Gurmu Y, McCague K, Rocha R, Braunwald E. Cardiovascular biomarkers in patients with acute decompensated heart failure randomized to sacubitril-valsartan or enalapril in the PIONEER-HF trial. European Heart Journal 2019, 40: 3345-3352. PMID: 31093657, PMCID: PMC6801941, DOI: 10.1093/eurheartj/ehz240.Peer-Reviewed Original ResearchConceptsSacubitril/valsartanAcute decompensated HFAcute decompensated heart failureSoluble ST2Decompensated heart failureHeart failureUrinary cGMPMyocardial stressHigh-sensitivity cardiac troponinCyclic guanosine 3'5PIONEER-HF trialDouble-blind trialReduced ejection fractionMultivariable-adjusted analysesGreater reductionNatriuretic peptide receptorPIONEER-HFCardiovascular deathCardiac afterloadHaemodynamic stabilizationEjection fractionHospitalized patientsMyocardial injuryCardiovascular biomarkersTreatment groupsClinical Outcomes in Patients With Acute Decompensated Heart Failure Randomly Assigned to Sacubitril/Valsartan or Enalapril in the PIONEER-HF Trial
Morrow DA, Velazquez EJ, DeVore AD, Desai AS, Duffy CI, Ambrosy AP, Gurmu Y, McCague K, Rocha R, Braunwald E. Clinical Outcomes in Patients With Acute Decompensated Heart Failure Randomly Assigned to Sacubitril/Valsartan or Enalapril in the PIONEER-HF Trial. Circulation 2019, 139: 2285-2288. PMID: 30955360, DOI: 10.1161/circulationaha.118.039331.Peer-Reviewed Original Research
2018
Angiotensin–Neprilysin Inhibition in Acute Decompensated Heart Failure
Velazquez EJ, Morrow DA, DeVore AD, Duffy CI, Ambrosy AP, McCague K, Rocha R, Braunwald E. Angiotensin–Neprilysin Inhibition in Acute Decompensated Heart Failure. New England Journal Of Medicine 2018, 380: 539-548. PMID: 30415601, DOI: 10.1056/nejmoa1812851.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAgedAminobutyratesAngiotensin Receptor AntagonistsAngiotensin-Converting Enzyme InhibitorsBiphenyl CompoundsCardiac Output, LowDose-Response Relationship, DrugDouble-Blind MethodDrug CombinationsEnalaprilFemaleHeart FailureHumansMaleMiddle AgedNatriuretic Peptide, BrainNeprilysinPeptide FragmentsStroke VolumeTetrazolesValsartanConceptsAcute decompensated heart failureDecompensated heart failureNT-proBNP concentrationsSacubitril-valsartan groupSacubitril-valsartan therapyReduced ejection fractionHeart failureSymptomatic hypotensionRenal functionEnalapril groupEjection fractionWeek 4N-terminal pro-B-type natriuretic peptide concentrationsAngiotensin-Neprilysin InhibitionKey safety outcomePrimary efficacy outcomeNatriuretic peptide concentrationsGreater reductionEnalapril therapyEfficacy outcomesHemodynamic stabilizationSafety outcomesBaseline valuesWeek 1PatientsAngiotensin receptor-neprilysin inhibitor therapy in heart failure: An end that justifies the means
Ambrosy AP, Velazquez EJ. Angiotensin receptor-neprilysin inhibitor therapy in heart failure: An end that justifies the means. American Heart Journal 2018, 199: 176-177. PMID: 29754658, DOI: 10.1016/j.ahj.2018.02.007.Peer-Reviewed Original ResearchRationale and design of the comParIson Of sacubitril/valsartaN versus Enalapril on Effect on nt-pRo-bnp in patients stabilized from an acute Heart Failure episode (PIONEER-HF) trial
Velazquez EJ, Morrow DA, DeVore AD, Ambrosy AP, Duffy CI, McCague K, Hernandez AF, Rocha RA, Braunwald E. Rationale and design of the comParIson Of sacubitril/valsartaN versus Enalapril on Effect on nt-pRo-bnp in patients stabilized from an acute Heart Failure episode (PIONEER-HF) trial. American Heart Journal 2018, 198: 145-151. PMID: 29653636, DOI: 10.1016/j.ahj.2018.01.004.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAgedAminobutyratesBiphenyl CompoundsCardiac Output, LowCause of DeathDose-Response Relationship, DrugDouble-Blind MethodDrug Administration ScheduleDrug CombinationsDrug Delivery SystemsEnalaprilFemaleHeart FailureHumansMaleMiddle AgedNatriuretic Peptide, BrainPatient SafetyPeptide FragmentsPrognosisProspective StudiesRisk AssessmentSeverity of Illness IndexSurvival RateTetrazolesTreatment OutcomeValsartanConceptsAcute decompensated heart failureSacubitril/valsartanB-type natriuretic peptideDecompensated heart failureAmino-terminal pro-B-type natriuretic peptideTerminal pro-B-type natriuretic peptideEjection fractionHeart failureHospital initiationNatriuretic peptideEnd pointClass angiotensin receptor neprilysin inhibitorAngiotensin receptor neprilysin inhibitorPg/Primary efficacy end pointAmbulatory HF patientsExploratory end pointsPIONEER-HF trialEfficacy end pointReduced ejection fractionSafety end pointOpen-label treatmentIncidence of angioedemaYears of agePIONEER-HF
2015
Angiotensin Receptor Neprilysin Inhibition in Heart Failure: Mechanistic Action and Clinical Impact
Buggey J, Mentz RJ, DeVore AD, Velazquez EJ. Angiotensin Receptor Neprilysin Inhibition in Heart Failure: Mechanistic Action and Clinical Impact. Journal Of Cardiac Failure 2015, 21: 741-750. PMID: 26209000, DOI: 10.1016/j.cardfail.2015.07.008.Peer-Reviewed Original ResearchConceptsHeart failureNeprilysin inhibitionClinical dataClinical impactAngiotensin receptor-neprilysin inhibitionRate of angioedemaAngiotensin receptor blockersEnzyme inhibitor enalaprilMechanistic actionImproved safety profileSignificant reductionARNi LCZ696Aldosterone systemHF patientsHF severityReceptor blockersCardiorenal effectsNeprilysin inhibitorHF populationNatriuretic peptideSafety profileACE inhibitionSurrogate markerClinical trialsCommon syndromeSex differences in clinical characteristics and outcomes after myocardial infarction: insights from the Valsartan in Acute Myocardial Infarction Trial (VALIANT)
Lam CS, McEntegart M, Claggett B, Liu J, Skali H, Lewis E, Køber L, Rouleau J, Velazquez E, Califf R, McMurray JJ, Pfeffer M, Solomon S. Sex differences in clinical characteristics and outcomes after myocardial infarction: insights from the Valsartan in Acute Myocardial Infarction Trial (VALIANT). European Journal Of Heart Failure 2015, 17: 301-312. PMID: 25655011, DOI: 10.1002/ejhf.238.Peer-Reviewed Original ResearchConceptsAcute Myocardial Infarction trialMyocardial Infarction trialVentricular systolic dysfunctionHeart failureMyocardial infarctionSystolic dysfunctionClinical characteristicsVentricular volumeKillip class III/IVLeft ventricular systolic dysfunctionRisk of HFClass III/IVHigher long-term riskSmaller left ventricular volumesSimilar ejection fractionLong-term mortalityPost-infarction anginaRisk of hospitalizationSubset of patientsNon-fatal outcomesLong-term riskLeft ventricular volumeAssociation of sexMore comorbiditiesCardiovascular death
2014
Impact of Cardiovascular Events on Change in Quality of Life and Utilities in Patients After Myocardial Infarction A VALIANT Study (Valsartan In Acute Myocardial Infarction)
Lewis EF, Li Y, Pfeffer MA, Solomon SD, Weinfurt KP, Velazquez EJ, Califf RM, Rouleau JL, Kober L, White HD, Schulman KA, Reed SD. Impact of Cardiovascular Events on Change in Quality of Life and Utilities in Patients After Myocardial Infarction A VALIANT Study (Valsartan In Acute Myocardial Infarction). JACC Heart Failure 2014, 2: 159-165. PMID: 24720924, DOI: 10.1016/j.jchf.2013.12.003.Peer-Reviewed Original ResearchMeSH KeywordsAcute DiseaseAgedAngiotensin II Type 1 Receptor BlockersAngiotensin-Converting Enzyme InhibitorsBundle-Branch BlockCaptoprilDeath, Sudden, CardiacDrug Therapy, CombinationFemaleHealth StatusHeart FailureHospitalizationHumansMaleMyocardial InfarctionQuality of LifeRecurrenceStrokeSurvivorsTetrazolesTreatment OutcomeValineValsartanConceptsNonfatal CV eventsEQ-5D assessmentCV eventsVisual analog scaleEQ-5D scoresCardiovascular eventsMyocardial infarctionEQ-5DBaseline EQ-5D scoresKillip class IINonfatal cardiovascular eventsHealth-related qualityLinear mixed-effects regression modelsQuality of lifeMixed effects regression modelsVALIANT studyWorse HRQLVAS scoresEjection fractionNonfatal eventsMI survivorsAnalog scaleVALIANT trialGeneric instrumentsPatients
2012
Mechanisms and Predictors of Mitral Regurgitation after High-Risk Myocardial Infarction
Meris A, Amigoni M, Verma A, Thune JJ, Køber L, Velazquez E, McMurray JJ, Pfeffer MA, Califf R, Levine RA, Solomon SD, Investigators V. Mechanisms and Predictors of Mitral Regurgitation after High-Risk Myocardial Infarction. Journal Of The American Society Of Echocardiography 2012, 25: 535-542. PMID: 22305962, PMCID: PMC3501447, DOI: 10.1016/j.echo.2012.01.006.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAngiotensin-Converting Enzyme InhibitorsCaptoprilDisease ProgressionEchocardiography, Doppler, ColorElectrocardiographyFemaleFollow-Up StudiesHumansMaleMiddle AgedMitral Valve InsufficiencyMonitoring, PhysiologicMultivariate AnalysisMyocardial InfarctionPredictive Value of TestsProspective StudiesReference ValuesReproducibility of ResultsRisk AssessmentROC CurveSeverity of Illness IndexSex FactorsStatistics, NonparametricStroke VolumeTetrazolesTime FactorsValineValsartanVentricular Dysfunction, LeftVentricular RemodelingConceptsHigh-risk myocardial infarctionBaseline mitral regurgitationMitral regurgitationMyocardial infarctionAtrial sizeIndependent predictorsCoaptation depthProgression of MRMitral valve deformationStructural valve diseaseSevere mitral regurgitationFunctional mitral regurgitationIschemic mitral regurgitationGood-quality echocardiogramsMitral annular areaMitral tentingMR degreeLV dysfunctionTenting areaBaseline characteristicsDiastolic functionHeart failureValve diseaseLV remodelingVentricular remodeling
2011
Predictors and prognostic impact of recurrent myocardial infarction in patients with left ventricular dysfunction, heart failure, or both following a first myocardial infarction
Thune JJ, Signorovitch JE, Kober L, McMurray JJ, Swedberg K, Rouleau J, Maggioni A, Velazquez E, Califf R, Pfeffer MA, Solomon SD. Predictors and prognostic impact of recurrent myocardial infarction in patients with left ventricular dysfunction, heart failure, or both following a first myocardial infarction. European Journal Of Heart Failure 2011, 13: 148-153. PMID: 21037250, DOI: 10.1093/eurjhf/hfq194.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAgedCaptoprilCause of DeathConfidence IntervalsDrug Therapy, CombinationFemaleFollow-Up StudiesHeart FailureHumansMaleMiddle AgedMultivariate AnalysisMyocardial InfarctionPredictive Value of TestsPrognosisProportional Hazards ModelsRecurrenceRisk AssessmentSeverity of Illness IndexSex FactorsSurvival AnalysisTetrazolesTime FactorsValineValsartanVentricular Dysfunction, LeftConceptsRecurrent myocardial infarctionFirst myocardial infarctionRisk of deathLeft ventricular dysfunctionMyocardial infarctionVentricular dysfunctionHeart failurePrognostic impactOne-year mortalityGlomerular filtration rateEarly reinfarctionLate reinfarctionTrial cohortUnstable anginaProlong survivalMedian timeMI survivorsFiltration ratePatientsContemporary managementContemporary treatmentInfarctionMortalityReinfarctionDeath
2010
Fatal myocardial rupture after acute myocardial infarction complicated by heart failure, left ventricular dysfunction, or both: The VALsartan In Acute myocardial iNfarcTion Trial (VALIANT)
Shamshad F, Kenchaiah S, Finn PV, Soler-Soler J, McMurray JJ, Velazquez EJ, Maggioni AP, Califf RM, Swedberg K, Kober L, Belenkov Y, Varshavsky S, Pfeffer MA, Solomon SD, Investigators F. Fatal myocardial rupture after acute myocardial infarction complicated by heart failure, left ventricular dysfunction, or both: The VALsartan In Acute myocardial iNfarcTion Trial (VALIANT). American Heart Journal 2010, 160: 145-151. PMID: 20598985, DOI: 10.1016/j.ahj.2010.02.037.Peer-Reviewed Original ResearchConceptsQ-wave myocardial infarctionMyocardial infarctionMyocardial ruptureClinical end-point committeeHigh-risk myocardial infarctionAcute Myocardial Infarction trialEnd-point committeeNonfatal cardiovascular eventsPresence of hemopericardiumQualifying MIMyocardial Infarction trialHigh-risk patientsGlomerular filtration ratePost-MI patientsAcute myocardial infarctionInferior myocardial infarctionDirect surgical visualizationKillip classCardiovascular eventsDiuretic useOral anticoagulantsVentricular dysfunctionClinical characteristicsFatal complicationHeart failureMechanical Dyssynchrony After Myocardial Infarction in Patients With Left Ventricular Dysfunction, Heart Failure, or Both
Shin SH, Hung CL, Uno H, Hassanein AH, Verma A, Bourgoun M, Køber L, Ghali JK, Velazquez EJ, Califf RM, Pfeffer MA, Solomon SD. Mechanical Dyssynchrony After Myocardial Infarction in Patients With Left Ventricular Dysfunction, Heart Failure, or Both. Circulation 2010, 121: 1096-1103. PMID: 20176989, DOI: 10.1161/circulationaha.109.863795.Peer-Reviewed Original ResearchMeSH KeywordsAgedAnalog-Digital ConversionAngiotensin II Type 1 Receptor BlockersDeathDisease ProgressionFemaleFollow-Up StudiesHeart FailureHumansMaleMiddle AgedMotionMyocardial ContractionMyocardial InfarctionPrognosisProportional Hazards ModelsStress, MechanicalTetrazolesUltrasonographyValineValsartanVentricular Dysfunction, LeftVideo RecordingConceptsSD of timeLeft ventricular dysfunctionHeart failureMyocardial infarctionMechanical dyssynchronyVentricular dysfunctionIndependent predictorsPost-myocardial infarction prognosisPeak velocityAdverse cardiovascular outcomesMultivariate Cox modelRisk of deathLeft ventricular segmentsMeasures of dyssynchronyVelocity vector imagingCardiovascular outcomesEchocardiographic variablesVentricular synchronyVentricular dyssynchronyClinical outcomesEchocardiography studyRisk factorsContractile patternsVentricular segmentsCox model
2009
Predictors of sudden cardiac death change with time after myocardial infarction: results from the VALIANT trial
Piccini JP, Zhang M, Pieper K, Solomon SD, Al-Khatib SM, Van de Werf F, Pfeffer MA, McMurray JJ, Califf RM, Velazquez EJ. Predictors of sudden cardiac death change with time after myocardial infarction: results from the VALIANT trial. European Heart Journal 2009, 31: 211-221. PMID: 19854729, DOI: 10.1093/eurheartj/ehp425.Peer-Reviewed Original ResearchConceptsSudden cardiac deathMyocardial infarctionInitial left ventricular ejection fractionRisk of SCDLeft ventricular ejection fractionHigher baseline heart rateBaseline creatinine clearanceBaseline clinical characteristicsRecurrent cardiovascular eventsPrior myocardial infarctionVentricular ejection fractionBaseline heart rateCox proportional hazardsCardiovascular eventsClinical characteristicsCreatinine clearanceCumulative incidenceCardiac deathEjection fractionEntire followRisk stratificationVALIANT trialPost-MIRisk stratifierLandmark analysisGastrointestinal bleeding in high risk survivors of myocardial infarction: the VALIANT Trial
Moukarbel GV, Signorovitch JE, Pfeffer MA, McMurray JJ, White HD, Maggioni AP, Velazquez EJ, Califf RM, Scheiman JM, Solomon SD. Gastrointestinal bleeding in high risk survivors of myocardial infarction: the VALIANT Trial. European Heart Journal 2009, 30: 2226-2232. PMID: 19556260, DOI: 10.1093/eurheartj/ehp256.Peer-Reviewed Original ResearchConceptsRisk factorsGastrointestinal bleedingGI bleedingWorse New York Heart Association classNew York Heart Association classAcute Myocardial Infarction trialPost-myocardial infarction patientsAdditional antiplatelet drugsProfound risk factorRate of GIAdjusted hazard ratioDual antiplatelet therapyMultivariable Cox modelMyocardial Infarction trialDual antiplatelet agentsLeft ventricular dysfunctionGlomerular filtration rateHigh-risk survivorsUse of antiplateletPost-MI patientsRisk of deathPotential risk factorsNon-white racePresent secondary analysisOccurrence of GI