Clinical Phenotypes and In-hospital Management and Prognosis in Diabetic versus Non-diabetic Patients with Acute Heart Failure in ALARM-HF Registry J T. Parissis, A. Mebazaa, V. Bistola, I. Ikonomidis, J. Delgado, F. Vilas-Boas, M. Anastasiou-Nana, D. Kremastinos, A. Mclean, F. Follath For ALARM-HF investigators
Disclosures Research grants by Abbott USA and Orion- Pharma as a member of steering committee of ALARM-HF Survey
Prevalence of Diabetes in Patients With Heart Failure: Clinical Trials Clinical Trial Diabetic Patients SOLVD 25.8% MERIT-HF 24.5% ELITE II 24.0% Val-HeFT 25.4% COPERNICUS 25.7% OPTIME-CHF (hospitalized) 44.2% VMAC (hospitalized) 47.0% SOLVD=Studies of Left Ventricular Dysfunction. MERIT-HF=Metoprolol Randomized Intervention Trial in Heart Failure. ELITE II=Evaluation of Losartan in the Elderly. Val-HeFT=Valsartan Heart Failure Trial. COPERNICUS=Carvedilol Prospective Randomized Cumulative Survival. OPTIME-CHF=Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure. VMAC=Vasodilation in the Management of Acute Congestive Heart Failure.
Relationship Between Diabetes and Heart Failure Prevalence: US population, 4%-6%; HF patients, 22%-48% Diabetes mellitus Heart failure
Insulin-Dependent Diabetes Is Associated With Increased Mortality in Patients With Advanced Heart Failure Survival (%) 100 80 60 40 20 DM, no insulin No DM P=0.0002 DM, insulin 0 0 1 2 3 4 5 6 7 8 9 10 11 12 624 patients with advanced HF and systolic dysfunction. Smooky and Fonarow, AHJ 2005. Months
DM and mortality in HF: clinical trial populations Mac Donald et al. Eur Heart J 2008;29: 1224 1240
Heart Failure Due to Systolic Dysfunction and Mortality in Diabetes: Pooled Analysis of 39,505 Subjects Kamalesh and Cleopas, J Card Fail 2009;15:305-309
DM and Hospitalizations in HF Kamalesh and Cleopas, J Card Fail 2009;15:305-309
Pathopysiologic mechanisms Diabetic cardiomyopathy (microvasculopathy, fibrosis, cellular hypertrophy) Diastolic dysfunction (abnormal collagen deposition, abnormal calcium handling) Ischemic cardiomyopathy (MI, chronic ischemia)
Mechanisms of heart dysfunction in DM Mac Donald et al. Eur Heart J 2008;29: 1224 1240
Prevalence of DM in AHF registries
Prognostic Impact of Diabetes Mellitus in Patients With Acute Decompensated HF (VMAC Trial) Am J Cardiol 2005;95:1117
Influence of diabetes on characteristics and outcomes in patients hospitalized with HF Greenberg et al. Am Heart J 2007;154:277.e1-277.e8.
ALARM-HF: a view of AHF management across a wide variety of countries ALARM-HF Study - 9 Country Panel Analysis patient case share by country 66% cardiology 33% ICU Australia 5% Mexico 12% France 12% Germany 12% Top 5 EU = 65% Turkey 13% Greece 5% Italy 14% UK 13% Spain 14% ALARM-HF 9 Country (4,953 patients)
EHS HF II vs ALARM: Underlying CV comorbidities Acute heart failure patient CV co-morbidities: All AHF vs ADCHF vs Novo AHF patients 80% 70% 60% 50% 40% 30% 20% 10% 0% 72% 70% 66% 63% 49% 45% 38% 33% 54% 34% 31% 25% EHS HF II All AHF ADCHF De novo 39% 32% 30% 25% 24% 14% 13% most common co-morbidities = hypertension (70%), diabetes (45%) Sample = All AHF patients (4,953) vs ADCHF (3,161) vs De Novo AHF patients (1,792) Follath et al. Intensive Care Medicine 2010
Diabetics vs Non Diabetics in ALARM-HF: demographics Clinical characteristics Diabetics Non diabetics p value Age (years) <0.0001 <55 10.2% 20.3% 56-80 76.8% 62.7% >80 13.0% 17.0% Sex 0.063 Male 59.8% 64.5% Female 40.2% 35.5% J Parissis on behalf of ALARM Steering Committee
ESC Clinical classification in Diabetics vs Non-Diabetics (ALARM-HF) p < 0.0001
Co-morbidities in diabetics vs nondiabetics with AHF Cardiovascular comorbidities Diabetics Non diabetics p value Chronic heart failure 41.6% 32.0% <0.0001 CAD 35.5% 26.7% <0.0001 Cardiomyopathy 10.5% 14.5% <0.0001 Atrial fibrillation/flutter 24.5% 24.3% 0.893 Peripheral vascular disease 11.6% 6.7% <0.0001 Obesity 34.5% 19.9% <0.0001 Dyslipidemia 53.0% 33.1% <0.0001 Hypertension 81.6% 60.8% <0.0001 Non cardiovascular comorbidities Chronic renal disease 29.5% 14.7% <0.0001 Anemia 16.8% 12.4% <0.0001 Depression 9.3% 7.9% <0.01 Dementia 4.6% 3.8% 0.179 Hyponatremia 7.7% 4.8% <0.0001 Asthma/COPD 29.3% 21.1% <0.0001 J. Parissis on behalf of ALARM investigators
In-hospital Mortality of Diabetics vs Non-Diabetics With AHF (ALARM-HF) 12 11,5 11 10,5 p = 0.03 10 Death 9,5 9 8,5 Diabetics Non diabetics
ACS as precipitating factor of AHF in Diabetics vs Non-Diabetics (ALARM-HF) 50 45 40 35 30 25 20 p < 0.0001 Acute coronary syndrome 15 10 5 0 Diabetics Non diabetics
AHF Therapies in Diabetics vs Non-Diabetics (ALARM-HF) p < 0.0001 p = 0.043
Treatment modalities in diabetics vs non-diabetics with AHF Interventional PCI 15.3% 10.8% <0.0001 CABG 3.8% 2.2% 0.001 ICD/CRTs 4.9% 4.7% 0.626 IABP 5.0% 4.7% 0.628 J. Parissis on behalf of ALARM investigators
Prognostic Factors in Diabetics with AHFS (ALARM-HF) Parameter OR 95%CI P Negative predictors Age 1.498 1.263-1.943 0.032 SBP<100 mmhg 20.029 8.720-46.003 <0.0001 Precipitating factors: ACS 1.379 0.947-2.00 0.05 Non compliance 1.163 1.046-1.573 0.005 Cardiovascular comorbidities: Arterial hypertension 2.564 1.143-5.753 0.022 Serum creatinine >1.5mg/dl 1.973 1.072-3.632 0.029 LVEF<50% 1.941 1.917-1.966 <0.0001 Length of stay in the CCU 1.997 1.994-2.000 0.021 Positive predictors Admission therapy: Beta-blocker 0.324 0.132-0.794 0.014 ACEi/ARB 0.143 0.054-0.380 <0.0001 Nitrates 0.207 0.041-1.038 0.056 PCI 0.193 0.083-0.448 <0.0001 J. Parissis on behalf of ALARM investigators
Conclusions Diabetes is highly prevalent in hospitalized patients with AHF. AHF patients with diabetes have more frequently underlying ischemic heart disease and multiple comorbidities. Diabetics with AHF have higher in-hospital mortality than non-diabetic patients despite their intensive treatment regimens. Age, LVEF, renal function, SBP, ACS and absence of life saving therapies at admission may identify high risk diabetics with AHF.