Presentation on theme: "Detection and management of preclinical heart failure"— Presentation transcript:
1 Detection and management of preclinical heart failure Tom MarwickDirector, Menzies Research Institute Tasmania
2 EARLY HEART FAILURE Preclinical heart failure Overt heart failure(Stages C and D)Preclinical diseaseStage BRisk factors including social determinants and behaviour (Stage A)
3 EARLY HEART FAILURE HF stages Stage AAt high risk for HF without structural heart disease or symptomsStage BStructural heart disease but without signs or symptoms of HFStage CStructural heart disease with prior or current symptoms of HFStage DRefractory HF requiring specialized interventionPatient with:-Hypertension-Atherosclerosis-Diabetes-Metabolic syndrome-Cardiotoxins-With FHx CMPatient with:-Previous MI-LV remodeling including LVH and low EF-Asymptomatic valvular diseaseHunt SA, et al. J Am Coll Cardiol 2009;53:e1-e90
4 EARLY HEART FAILURE TCF funding – Rural HF project Why - The epidemiology of heart failureDetection - is HF screening an option?Right populationRight testRx strategyMeasuring outcomesQuantifying risk, FP and FN resultsProof of Principle – TasELF studyLessons about community-based RCTs
5 EARLY HEART FAILURE What is heart failure? Chronic heart failureAcute heart failure
6 EARLY HEART FAILURE Magnitude of the Problem Australia (National Heart Foundation of Australia-HF guideline)Prevalence: 10% (> 65 yrs); 50% (> 85 yrs )Annual Incident HF: 30,000Annual admissions: 100,000Annual cost of care: $411 million (0.4% )USA (Hunt SA ,2009)Prevalence: 5,800,000Incident rate: 500,000 /yearAnnual cost of care: 39 billion (1-2%)Worldwide (McMurray JJ 1998)Prevalence: 23,000,000Why is HF increasing?- Aging- Survival from heart attack- Risk factorsBPdiabetesobesity
7 EARLY HEART FAILURE The heart failure epidemic HF IS THE SINGLE MOST EXPENSIVE DIAGNOSIS IN HEALTH SYSTEMHospital admissions per 1,000 population per year for heart failure (Kannel WG. Br Heart J 1994)Chance of getting HF?- About 30%Why is HF increasing?- Aging- Survival from heart attack- Risk factorsBPdiabetesobesity
8 EARLY HEART FAILURE Metabolic drivers of the HF epidemic Wellcome Museum, London
9 EARLY HEART FAILURE HF – Survival rate at 5 years Five-year survival following a first admission to any Scottish hospital in 1991 for heart failure, myocardial infarction and the four most common of cancer specific to men and women.Stewart S, et al. More malignant than cancer? Five-year survival following a first admission for heart failure in Scotland. European Journal of Heart Failure 3 (2001)
10 Heart Failure - Quality of Life EARLY HEART FAILUREHeart Failure - Quality of LifePF: Physical functionRP: Role limitationBP: Body painGH: General health perceptionsVT: VitalitySF: Social functionRE: Emotional ProblemsMH: Mental HealthLynn J. JAMA 1997; 277:Juenger J et al. Health related quality of life in patients with congestive heart failure: comparison with other chronic disease and relation to functional variables.Heart 2001; 87: 235
11 EARLY HEART FAILURE HF is bad! What can we do about it? Focus on early disease to change trajectory
12 EARLY HEART FAILURE TCF funding – Rural HF project Why - The epidemiology of heart failureDetection - is HF screening an option?Right populationRight testRx strategyMeasuring outcomesQuantifying risk, FP and FN resultsProof of Principle – TasELF studyLessons about community-based RCTs
13 EARLY HEART FAILURE Screening for HF Prevalence: 10% (> 65 yrs)At June 2010, there were 79,100 people aged 65 years and over in Tasmania % of the populationCan we afford to screen ~80,000 people in order to find ~8,000 with HF?
14 EARLY HEART FAILURE What’s wrong with screening? The risk of false positive resultsLead to further unnecessary diagnostic testing, over-treatment, some can be invasiveCause psychological distress and anxiety in asymptomatic peopleNeed of evidence that screening and detection changes management outcomesScreening for Heart Failure has not been recommended by the US Preventive Services Task Force
15 EARLY HEART FAILURE Essentials of screening Thomas Bayes,Choosing the right populationHaving the right testAbsolute vs relative riskDefining the phenotypeHaving a treatment strategyKnowing how to manage false positive and false negative tests
16 EARLY HEART FAILURE Rural HF project Why - The epidemiology of heart failureDetection - is HF screening an option?Right populationRight testRx strategyMeasuring outcomesQuantifying risk, FP and FN resultsProof of Principle – TasELF study
21 EARLY HEART FAILURE PRISMA- A Meta Analysis Total articles identified(n=2947)Articles reviewed by title or abstract(n=1974)Articles included for meta-analysis(n=23)Articles included in systematic review(n=29)18 additional articles from bibliographies included. Articles for full text review(n=111)Articles eligible for review(n=94)Excluded duplicates(n=973)Excluded by title or abstract(n=1880)Excluded articles not reporting characteristics of inclusion criteria(n=83)Excluded articles reporting risk inconsistent with inclusion criteria(n=6)Inclusion:Study in unselected population, communityReporting risk effect size in RR/OR/HROutcome: incident heart failure
22 EARLY HEART FAILURE Studies included AuthorStudy (Trial)Total(n)F-U(year)HF1Ho;Kannel ;Ho et alFramingham study (Framingham and Offspring)9450406522ButlerKalogeroulHealth ABC study (Health Aging and Body Composite Study)29346.52583HeNHANES (National Health Nutrition Examination Survey136431913824ErikssonMen born in 1913 (Sweden)973173115AgarwalARIC (The Atherosclerosis Risk in Communities)1355515.514876GoyalOne Million Person-Year35994740017DunlayPopulation based CC-Mayo19249628BahramiMESA (Multi-Ethnic Study of Atherosclerosis)6814799Gottdiener; MujibCardio Vascular Health56251259710Chen YTEPESE (Established Population for Epidemiologic Studies of the Elderly program)174917311WilhelmsenMPPS (Sweden)749527937Bibbins-DCARDIA (Coronary Artery Risk Development in Young Adults)51152013IngelssonULSAM23212925914Wang JKuopio (Finland)103220.730315AronowMt Sinai29023.5879416Smith JGMDCS (Sweden)5187112KenchaiahPhysician’s heart (US)2109421110918BrouwersPREVEND (Netherlands) 859212 374
25 EARLY HEART FAILURE Inclusion/ Exclusion > 65 yearsDiabetesHigh blood pressure /on treatmentOverweightFamily history of heart failurePast history of chemotherapyPast history of heart diseaseInclusion< 65 years> Moderate valve diseaseHistory of heart failureAlready on BB and ACEiContraindications to BB or ACEiOncologic life expectancy <12 monthInability to acquire adequate imagesExclusion
26 EARLY HEART FAILURE Rural HF project Why - The epidemiology of heart failureDetection - is HF screening an option?Right populationRight testRx strategyMeasuring outcomesQuantifying risk, FP and FN resultsProof of Principle – TasELF studyLessons about community-based RCTs
27 BNP release from Cardiac Myocytes EARLY HEART FAILUREBNP release from Cardiac MyocytespreproBNP (134 aa)myocyteproBNP (108 aa)signal peptide (26 aa)secretionNT-proBNP (1-76)BNP (77-108)
28 EARLY HEART FAILURE BNP to ER presentation with dyspnea N=139 N=14 N=97Maisel A. J Am Coll Cardiol 2001
29 Preclinical disease and BNP EARLY HEART FAILUREPreclinical disease and BNPn=101 apparently normal diabetic subjects (asymptomatic, normal EF)BNP in LVH pts was higher than those without LVHBut only 4 had elevated BNP (using age and gender-specific normal ranges) - only 1 had low velocity/strainBNP is not a good marker of subclinical disease (no substitute for the echo lab!)Fang ZY. Am Heart J 2005p<0.05NT-proBNP (pg/ml)Taylor A. Am Heart J 2006
30 EARLY HEART FAILURE Echo is essential in HF diagnosis My field of research is understanding the genes contributing to disease in particular famililial cancersSiemensSC2000Philipsie33GEVivid e9
31 EARLY HEART FAILURE Progressive miniaturization
32 EARLY HEART FAILURE Early HF – Standard tests normal LA volume32ml/m2
34 EARLY HEART FAILURE Strain and sick heart muscle
35 EARLY HEART FAILURE Other diagnostic markers? Central Blood PressureECG6 Minute-walk Test (6MW)Assessment of Activity and quality of lifeMinnesota MLHFQ scoreCharlson comorbidity indexDuke Activity Status Index (DASI)EQ5DSOF frailty score
36 EARLY HEART FAILURE Rural HF project Why - The epidemiology of heart failureDetection - is HF screening an option?Right populationRight testRx strategyMeasuring outcomesQuantifying risk, FP and FN resultsProof of Principle – TasELF study
37 Stage B Heart failure cardio-protective Treatment (SOLVD trial) SOLVD – Prevention TrialStudy of Left Ventricular DysfunctionThere was no difference between the carvedilol and placebo groups in the primary endpoint of all-cause mortality or hospital admission for cardiovascular problems (HR = .92 ; CI = ).percentage of event, defined as death or hospitalization for congestive Heart Failure, occurring in the placebo and Enalapril (ACEi) Groups
38 Cardio-protective Treatment of Stage B Heart failure (SAVE trial) SAVE Trial - CaptoprilStudy of Survival and Ventricular Enlargement TrialThere was no difference between the carvedilol and placebo groups in the primary endpoint of all-cause mortality or hospital admission for cardiovascular problems (HR = .92 ; CI = ).
39 EARLY HEART FAILURE Rural HF project Why - The epidemiology of heart failureDetection - is HF screening an option?Right populationRight testRx strategyMeasuring outcomesQuantifying risk, FP and FN resultsProof of Principle – TasELF study
40 EARLY HEART FAILURE Stage B HF - Progression to overt HF Aaron M. From et al. The development of Heart Failure in Patients with Diabetes Mellitus and Preclinical Diastolic Dysfunction: A Population Based Study. JACC ; 55(4)Natural history of SBHFOlmsted County study (n=1760)LV dysfunction in T2DM25% HF in 2 years, 36.9% in 5 years, twice the rate of HF in patients without LV dysfunction
41 TASELF Process Measures EARLY HEART FAILURETASELF Process Measures(n)
42 EARLY HEART FAILURE Rural HF project Why - The epidemiology of heart failureDetection - is HF screening an option?Right populationRight testRx strategyMeasuring outcomesQuantifying risk, FP and FN resultsProof of Principle – TasELF study
43 EARLY HEART FAILURE Changes needed MedicareTasmania Medicare LocalDHHSTHOs“55113 – Cardiac M-mode and 2 dimensional real time echocardiographic examination of the heart … for the investigation of symptoms or signs of cardiac failure, orsuspected or known ventricular hypertrophy or dysfunction, or chest pain”
44 EARLY HEART FAILUREResearch Questions1. What is the prevalence of Stage B Heart Failure (LVSD & LVDD) in at risk population in Tasmanian community2. How does functional capacity (6MW test) correlates with echo systolic and diastolic parameters3. How does central blood pressure associate with diastolic dysfunction and LV mass4. What is a better echo marker LVEF, GLS and diastology in stage B heart failure.5. How does screening and early treatment affect quality of life?6. Is community screening cost effective?7. What are the main constrains of a community screening model? Main constrains of treatment delivery.
45 TASELF - Study designTitleTasmanian Study of Echocardiographic detection of Left ventricular dysfunctionTrial acronymTAS-ELF (H )Trial IDACTRNStudy TypeInterventional (Prospective Randomized Open Blinded Endpoint-Probe)AllocationRandomized Controlled (Adaptive)Sample size400 x 400 (=0.044, β=0.8; 7.8% annual loss); 25% versus 12.5% in 2 yrsRandom seq. Masking/blindEnrollment followed by randomization (central web-based program).Masked: those involved in recruiting, randomization, analyzing data.ParticipantsEligibility: (>65 year, Stage A[ACC/AHA guideline]); Exclusion: BB + ACEiRecruitment18 months. Self-referred (by advertising and recommendation by GP)Follow UpPhone tracking on 1st, 6th,12th,18th,24th month. Repeat assessment: 24th month.PrimarySecondaryNew onset of heart failure;6 minutes walk test distance
48 EARLY HEART FAILURE Planned protocol Apparently healthy subject with HF riskExclusion of known HF, co-morbidities, CADSubclinical LVD – start ACEi and BB(n=120)Normal LV2 year follow-up for HF and functional capacityClinically suitable for randomizationClinical questionnairesUsual careExclusion of reduced EF (<40%), valve disease, CADBNP in borderlineBaseline echoRandomize1:1 (n=800)Echo strain, diastologyHF 25%HF 10%HF 5%Aim to study 800 subjects in the 1st year (400 subjects with HF screening and therapy vs 400 controls)~16 studies per week (ie 2 trips/week)
50 TASELF Registry – updated May 2014 Assessed for eligibility(n=511)Randomized(n=220)AllocationAllocated to intervention (=104)- Treatment (n=76)- Observation (Normal echo) (n=28)Allocated to observation (n=116)- Treatment (n=2)- Observation (n=114)Excluded (n=178)Not meeting inclusionParticipant registered (n=828)
51 EARLY HEART FAILURE The Big Picture At June 2010, there were 79,100 people aged 65 years and over in Tasmania % of the populationThe prevalence of people in this age group with diabetes (T2DM), obesity, high blood pressure, past cancer therapy or known cardiac disease is about 50% - roughly 40,000 people (100 times the number in the study)An effective program on a state-wide basis would avoid/delay heart failure in 2,400 people.
52 EARLY HEART FAILURE Stakeholders Impact of project on stakeholdersProf Marwick and Ms YangSupport of their research activitiesMenzies Research Institute TasmaniaLeadership of a community-based initiative that aligns with the mission of the InstituteRural GPsAccess to diagnostic testing that may help identify and avoid patients developing a potential problem with heart failureRural communitiesAccess to a service that will reduce the risk of serious illness and hospital admission far away from their family/social supportConsultants/hospitalsReduction of urgent heart failure admissionsWider communityIf successful, the proposed strategy will be of value in all practices and not restricted to the rural community
53 EARLY HEART FAILURE Support ItemAmountSourceContribution to Echo equipment$150,000Tas Community Fund$105,000SiemensSonographer PhD scholarship$75,000National Heart FoundationSupervision – Principal investigator, cardiologists, GPs$50,000+Menzies, THO-S, practicesSupport of travel, research assistants$50,000$40,000Diabetes AustraliavTAHSPTotal~$500k
55 EARLY HEART FAILURE Rural HF project Why - The epidemiology of heart failureDetection - is HF screening an option?Right populationRight testRx strategyMeasuring outcomesQuantifying risk, FP and FN resultsProof of Principle – TasELF studyLessons about community-based RCTs
56 EARLY HEART FAILURE Time frame TasksResponsible personStart dateDue dateMilestonesCommunication with GPs, advertising to communitiesProf Tom Marwick, Dr Michael Lees1st July 201330th June 2014Recruitment of ~10 communitiesEthics applicationProf Tom Marwick17th July 2014ApprovalScreening and imaging in communitiesMs Hilda Yang, other members of Prof Tom Marwick’s teamScreening of subjects in 12 monthsTreatment of patients with undiagnosed diseaseDr Michael Lees, GPs in other communities, supported by Dr Jeff Evans, Prof Marwick, RHH and LGH cardiologists30th July 2016Appropriate management of identified patientsFollow-up at 12, 24, 36 months1st July 201430th June 2016Follow-up of screened subjectsData analysisProf Tom Marwick, Hilda Yang1st July 2016Complete analysisDissemination of resultsDecember 2016Submission to Australian and international symposia and publicationTranslation of science to practiceImplementation of screening programme Statewide
57 HEART FAILURE IN RURAL COMMUNITIES Risk evaluation LikelihoodSeriousnessMitigation planFailure to recruit practices in other townsLowSeriousContacts already being madeFailure to recruit appropriate patientsDirect approaches to communitiesLoss of patients to follow-upLess then expectedincidence of eligible pts fitting screening criteriaModerateIncrease recruitmentLess incidence of early stage HF than expectedVery unlikely - that would be an excellent outcome!Lower success than anticipated in reducing % that develop late stage HFNone – this would be a negative study. The community still have the benefit of vascular screening.Lack of buy-in from Government Agencies to implement programmeModerate if the effect is less than anticipatedInvolvement of the Heart Foundation and Diabetes Australia to help make our case with government.
58 EARLY HEART FAILURE Implications of Early HF 1,760 diabetic pts with assessment of cardiac function; 411 (23%) abnormalEvery 1-U increase in E/e' ratio a/w increase of HF hazard ratio of 3%Diastolic dysfunction a/w HF after adjustment for age, sex, BMI, HT, CAD and echo parameters (HR: 1.61; p = 0.003).From AM et al. J Am Coll Cardiol 2010
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