HF-PEF: Symptoms, quality of life and mortality/morbidity May 21, 2011 John McMurray, MD Eugene Braunwald Scholar in Cardiovascular Diseases, Brigham & Women s Hospital Boston; Visiting Professor of Medicine, Harvard Medical School. FINANCIAL DISCLOSURE: None relevant to this presentation CHARM ESC Hotline 030829 1
Presentation Outline Source of data Symptoms and signs Quality of life Clinical outcomes
What data to compare HF-PEF with HF-REF? Epidemiologic studies? Clinical trials?
What data to compare HF-PEF with HF-REF? Epidemiologic studies? Clinical trials? - DIG - CHARM - I-Preserve
DIG-Preserved vs. I-Preserve I-Preserve DIG low LVEF DIG-Preserved 25 30 35 40 45 50 55 60 LVEF (%)
Preserved vs. I-Preserve I-Preserve CHARM low LVEF Preserved 25 30 35 40 45 50 55 60 LVEF (%)
HF-REF vs. HF-PEF trials: baseline characteristics % DIG- Preserved (n=988) DIG- Low EF (n=6800) Preserved (n=3023) Low EF (n=4576) I-Preserve (n=4133) Mean age (yr) 67 64 67 65 72 75 yr (%) 23 15 27 20 34 Women (%) 41 23 40 26 60 SBP (mmhg) 138 126 136 127 136
HF-REF vs. HF-PEF trials: heart failure etiology DIG- Preserved (n=988) DIG- Low EF (n=6800) Preserved (n=3023) Low EF (n=4576) I-Preserve (n=4133) % Ischemic 59 71 57 65 25 Hypertensive 23 9 23 7 64
HF-REF vs. HF-PEF trials: co-morbidity % DIG- Preserved (n=988) DIG- Low EF (n=6800) Preserved (n=3023) Low EF (n=4576) I-Preserve (n=4133) Hypertension 60 45 64 49 88 Diabetes 29 28 28 29 27 Atrial fibrillation - - 29 26 29
Presentation Outline Source of data Symptoms and signs Quality of life Clinical outcomes
35 30 25 20 15 10 5 % CHARM: Baseline signs, symptoms and radiographic findings Alternative Added Preserved 0 Oedema Orthopnoea PND Rest dyspnoea S 3 Crackles JVP >6 cm Cardiomegaly
Presentation Outline Source of data Symptoms and signs Quality of life Clinical outcomes
Minnesota Living With Heart Failure Questionnaire Most extensively used and validated quality of life instrument in heart failure 21 item questionnaire physical and emotional dimensions; score 0-5 per item (0=none; 5 very much) Possible score 0-105 (lower score better QoL) Men better QoL than women; older patients better QoL than younger patients
QoL in HF: reduced vs preserved EF Distribution (%) 16 14 12 10 8 6 4 2 0 Minnesota Living with Heart Failure Summary Score Range HF-Preserved EF HF-Low EF 0-<10 10-<20 20-<30 30-<40 40-<50 50-<60 60-<70 70-<80 80-<90 >90 Better quality of life Worse quality of life Lewis et al. Eur J Heart Failure 2007;9:83-91
MLwHF: HF-REF and HF-PEF compared (lower score is better) HF-PEF CHARM preserved EF: median 40 (IQR 20-60) I-PRESERVE: mean MLwHF score 42.4 (SD 20.7) HF-REF CHARM low EF: median 39 (IQR 21-59) CARE-HF: 45.4 (SD 21.2) Val-HeFT : 32.4 (SD 23) ELITE (an elderly low EF population): mean score ~ 24.5 (SD ~20)
Presentation Outline Source of data Symptoms and signs Quality of life Clinical outcomes
Mortality and morbidity Low EF vs. Preserved CV death CHF hospitalization Proportion of patients (%) 35 30 25 20 15 10 5 0 Low EF Preserved 0 6 12 18 24 30 36 42 48 months Proportion of patients (%) 35 30 25 20 15 10 5 0 Low EF Preserved 0 6 12 18 24 30 36 42 48 months
HF-REF vs. HF-PEF: All-cause mortality DIG and CHARM Rate per 1000 patient years 140 120 120 115 111 100 80 76 60 54 40 20 0 DIG-REF (overall) DIG-PEF (overall) CHARM Alternative (placebo) Added (placebo) Preserved (placebo)
HF-REF vs. HF-PEF: HF hospitalization DIG and CHARM Rate per 1000 patient years 140 120 127 128 110 100 80 73 69 60 40 20 0 DIG-REF (overall) DIG-PEF (overall) CHARM Alternative (placebo) Added (placebo) Preserved (placebo)
HF-REF vs. HF-PEF: All-cause mortality CHARM and I-Preserve Rate per 1000 patient years 140 120 100 80 115 111 60 54 53 40 20 0 Alternative (placebo) Added (placebo) Preserved (placebo) I-Preserve
HF-REF vs. HF-PEF: HF hospitalization CHARM & I-Preserve Rate per 1000 patient years 140 128 120 111 100 80 69 60 40 43 20 0 Alternative (placebo) Added (placebo) Preserved (placebo) I-Preserve
Do these patients really have heart failure? Hypertensive, overweight women with swollen ankles Outcomes in HF-PEF compared to other populations.
I-PRESERVE patients versus those in other clinical trials What are the outcomes of patients in I-PRESERVE compared to patients in other cardiovascular disease trials?
Trial Inclusion n Age Female Systolic BP (year) (%) (mmhg) ACTION angina 7665 63 20 137 35 years proven CHD ACCORD diabetes 10251 62 39 136 CV disease/ risk factors ALLHAT hypertension 33357 67 47 146 55 years 1 CHD risk factor ANBP-2 hypertension 6083 72 51 168 65-84 years LIFE hypertension 9193 67 54 174 55-80 years LVH VALUE hypertension 15245 67 42 155 50 years CV dis./risk fact. HYVET hypertension 3845 84 60 173 80 years I-PRESERVE HF-PEF 4128 72 60 137 60 years HF-PEF 3023 67 40 136 Preserved
All-cause mortality Rate per 1000 patient years 60 50 40 47.2 52.5 30 25.6 28.7 20 10 0 11.4 15.7 16.4 17.3
All-cause mortality Rate per 1000 patient years 60 50 40 47.2 52.5 30 25.6 28.7 20 10 0 11.4 15.7 16.4 17.3
Heart failure hospitalization rates Rate per 1000 patient years 60 50 43 40 30 20 10 4.6 5.3 5.5 7.1 7.5 11.0 11.5 0 * fatal or non-fatal HF
Programme: cause of death by LVEF Annualized Incidence (%) 20 15 10 5 n = 1560 n = 1530 n = 1489 n = 1520 Non CV death Sudden Death HF Death Fatal MI Stroke Other CV Death n = 1500 Proportion of deaths non-cv 0 EF <25% EF 26-33% EF 34-40% EF 41-52% EF >53% Ejection Fraction 15% 18% 20% 21% 37% Solomon et al Circ 2005
Rates of hospital admission for any cause, all cardiovascular reasons, heart failure only and non-cardiovascular reasons* Alternative Admissions/patient/yr 1.6 1.4 1.2 1 0.8 0.6 0.4 0.2 Preserved Admissions/patient/yr 1.6 1.4 1.2 1 0.8 0.6 0.4 0.2 0 All CV HF Non-CV 0 All CV HF Non-CV *Placebo group
Summary and conclusions Compared with HR-REF, patients with HF-PEF are older and more frequently female, overweight and hypertensive. However, contrary to popular belief, certain co-morbidities such as diabetes, anemia and AF are similar (others are not e.g. COPD). Symptoms, quality of life and common laboratory measurements are similar (although neurohumoral activation less marked in HF-PEF than in HF-REF). Mortality and morbidity rates lower in HF-PEF The relative proportion of both fatal and non-fatal non-cv events is greater in HF-PEF (compared with HF-REF).