Suy tim với chức năng tâm thu thất trái bảo tồn Những vấn đề còn thách thức
TS.BS. Hoàng Văn Sỹ Đại học Y Dược Tp. Hồ Chí Minh Khoa Nội Tim mạch BV Chợ Rẫy
TP HCM 13/7/2019
Tần suất suy tim với EF bảo tồn (HFpEF)
Khoảng ½ bệnh nhân suy tim có triệu chứng là suy suy tim EF bảo tồn
In patients with clinical HF, the prevalence of HFpEF is estimated to be approximately 50%1
Patients with HFpEF were older and more likely to be female than those with HFrEF3a
The proportion of incident cases of HFpEF increased from 47.8% in 2000–2003 to 52.3% in 2008–20102
Vào 2020, ước đoán 65% suy tim nhập viện là suy tim EF bảo tồn4
aThe GWTG-HF registry was merged with claims from the U.S. Centers for Medicare and Medicaid Services (CMS) from January 1, 2005, through December 30, 2009, with 5 years of follow-up through the end of December 2014 HF, heart failure; HFrEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction.
1. Yancy CW et al. Circulation. 2013;128:e240-e327; 2. Gerber Y et al. JAMA Intern Med. 2015;175(6):996-1004; 3. Shah KS et al. J Am Coll Cardiol. 2017;70(20):2476-2486; 4. Oktay AA et al. Curr Heart Fail Rep. 2013; 10(4): doi:10.1007/s11897-013-0155-7.
Định nghĩa các loại suy tim theo ESC
Cơ chế bệnh sinh còn chưa rõ ?
1
Suy tim EF bảo tồn là biểu hiện của 1 bệnh ?
Hypertension and coronary artery disease are major risk factors for development of heart failure
Age
LV enlargement
Smoking
Systolic dysfunction
Dyslipidemia
HFrEF is also called systolic HF, although patients may also exhibit diastolic abnormalities
HFrEF
CAD/MI
Hypertension HFpEF Obesity
LV hypertrophy
Diabetes
Diastolic dysfunction
HFpEF is also called diastolic HF, although most patients have evidence of both systolic and diastolic dysfunction
Normal LV structure and function
LV remodeling
Subclinical LV dysfunction
Clinical HF
Years
Years/months
CAD, coronary artery disease; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; LV, left ventricular; MI, myocardial infarction.
1. Krum H, Gilbert RE. Lancet 2003;362:147–58; 2. Borlaug BA, Paulus WJ. Eur Heart J.2011;32:670–679.
Sinh bệnh học của HFpEF Các cơ chế SBH trung ương và ngoại vi Suy tim EF bảo tồn là biểu hiện của nhiều bệnh ?
Pulmonary
Pulmonary venous hypertension ± Impaired diffusion capacity ± ‘Reactive’ arterial hypertension
Peripheral Mechanisms
LV Diastolic Stiffening and Dysfunction
Renal
Sodium retention
LV Filling Pressures
RV Filling Pressures
• Heterogeneity of patient characteristics, organ- system involvement and number of pathophysiological abnormalities suggest a multifactorial etiology in patients with HFpEF
Endothelial dysfunction
RV Dysfunction
AF and LA Dysfunction
Central Mechanisms
Exercise tolerance
Load sensitivity
Autonomic dysfunction
Arterial Stiffening
• Subphenotypes in HFpEF are usually described according to the most dominant clinical characteristics:
LV Systolic Stiffening and Dysfunction
Coronary and systemic microvascular rarefaction
Skeletal muscle Myopathy
• HFpEF subphenotype with PAH and RV dysfunction has been well characterized and signifies advanced stage HF
AF, atrial fibrillation, LA, left atria; LV, left ventricular; RV, right ventricular; HFpEF, heart failure with preserved ejection fraction; PAH, pulmonary arterial hypertension
Zakeri R and Cowie MR. Heart 2018;104(5):377-384
Kiểu hình lâm sàng và bệnh lý đi kèm trong HFpEF
Tăng huyết áp là yếu tố nguy cơ chính của HFpEF1
Anemia
COPD
The most commonly encountered clinical phenotypes of HFpEF include hypertension (identified as the core risk factor), aging, obesity, pulmonary hypertension, and CAD1,2
Aging
Atrial Fibrillation
Frailty
Hypertension
CAD
PH
These clinical phenotypes further share comorbid conditions that include atrial fibrillation, anemia, COPD, frailty, diabetes, obstructive sleep apnea, and CKD2
• Aging-related comorbid conditions include atrial fibrillation,
anemia, COPD and frailty
Obesity
• Obesity-related comorbid conditions include diabetes,
CKD
Diabetes
obstructive sleep apnea and CKD
Obstructive sleep apnea
Defining clinical phenotypes could be essential for management of patients with HFpEF leading towards therapeutic progress
CAD, coronary artery disease, CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; HFpEF, heart failure with preserved ejection fraction; PH, pulmonary hypertension.
1. Yancy CW et al. Circulation. 2013;128:e240-e327. 2. Samson R. et al. J Am Heart Assoc. 2016;5(1):e002477. doi:10.1161/JAHA.115.002477.
Chẩn đoán HFpEF còn khó khăn ?
2
Chẩn đoán suy tim EF bảo tồn dựa trên cơ chế hay dựa trên khía cạnh lâm sàng ?
Dựa trên cơ chế1:
Áp lực động mạch phổi bít
Kishan S, et al. JACC: HEART FAILURE. VOL.6,NO.8,2018
1. Zakeri R, Cowie MR. Heart2018;0:1–8. doi:10.1136/heartjnl-2016-310790
Chẩn đoán HFpEF còn khó khăn ?
2
Chẩn đoán suy tim EF bảo tồn dựa trên cơ chế hay dựa trên khía cạnh lâm sàng ?
Dựa trên lâm sàng1:
▪ Obese HFpEF/HFpEF with pulmonary vascular disease ▪ HFpEF with arterial stiffening ▪ HFpEF with endothelial dysfunction.
Kishan S, et al. JACC: HEART FAILURE. VOL.6,NO.8,2018
1. Zakeri R, Cowie MR. Heart2018;0:1–8. doi:10.1136/heartjnl-2016-310790
Triệu chứng và dấu hiệu HFpEF
Triệu chứng tương tự suy tim EF giảm
The main differences are that patients with HFpEF have lower rates of acute pulmonary edema and paroxysmal nocturnal dyspnea
96.2
94.9
120 P = 0.11
100
)
%
80
( s t n e
P = 0.06
i t a P
46.4
42.5
30.1
25
21.1
17.3
60 P = 0.007 P = 0.02 40
20
Reduced ejection fraction (<40%) (n=1,570)
Preserved ejection fraction (>50%) (n=880)
HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; S3, third heart sound; S4, fourth heart sound.
0 Dyspnea or shortness of breath Orthopnea Paroxysmal nocturnal dyspnea Acute pulmonary edema
Bhatia RS, et al. N Engl J Med. 2006;355(3):260–269.
Triệu chứng và dấu hiệu HFpEF
Triệu chứng tương tự suy tim EF giảm
The main differences are that patients with HFpEF have lower rate of S3 heart sounds and chest radiographic signs and a higher rate of bilateral ankle edema
P = 0.95
90
84.3
P<0.001
P = 0.02
80
84.4
)
P = 0.03
70
66
%
61.3
P = 0.003
56.6
60
51.8
57.5
45.6
50
40.9
47
( s t n e i t a P
40
P = 0.002
30
20
12.5
10
0
8.4
Reduced ejection fraction (<40%) (n=1,570)
Preserved ejection fraction (>50%) (n=880)
HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; S3, third heart sound; S4, fourth heart sound.
Bilateral ankle edema Neck-Vein distension Pulmonary edema Pleural effusion Presence of S3 Crackles or rales on lung examination
Bhatia RS, et al. N Engl J Med. 2006;355(3):260–269.
Lưu đồ chẩn đoán suy tim
Siêu âm tim là bắt buộc để chẩn đoán suy tim
1. Ponikowski P, et al. Eur J Heart Fail. 2016 doi: 10.1002/ejhf.592
Đồng thuận ESC HFpEF: Điểm chẩn đoán và khả năng bị HFpEF
•The ESC is developing an Heart Failure Association Pre-test probability, Echocardiography, Further advanced work-up, and Final etiology (HFA-PEFF) score •This was presented at the Heart Failure Congress in 2018, but at the time of this recording, the manuscript was not published
Pieske B. ESC HFA Congress 2018. Abstract
Thang điểm mới chẩn đoán HFpEF: H2FPEF
https://www.mdcalc.com/h2fpef-score-heart-failure-preserved-ejection-fraction#next-steps
Thang điểm mới chẩn đoán HFpEF: H2FPEF
•The odds of HFpEF double for each 1 unit score increase •The maximum number of points is 9 and that correlates to a probability of HFpEF that goes above 95%
Reddy YNV et al. Circulation 2018;138:861-870
HFpEF có tiên lượng xấu ?
3
Suy tim EF bảo tồn có tiên lượng giống Suy tim EF giảm ?
Overall mortality in HFpEF compared to other cardiovascular trials
HF hospitalization in HFpEF compared to other cardiovascular trials
80
80
70
70
76 73
Other CV trials
CV trials
69
HFpEF trials
HFpEF trials
60
60
s r a e y t n e
s r a e y t n e
50
50
54 53
40
40
30
30
47.2 43
20
20
28.7 25.6
i t a p 0 0 0 1 r e p e t a R
i t a p 0 0 0 1 r e p e t a R
10
10
0
0
15.7 16.4 17.3 11.4 11.5 11 7.1 7.5 5.3 5.5 4.6
ACCORD ANBP-2 ACTION LIFE VALUE ALLHAT HYVET I-Preserve CHARM-P DIG-PEF
ACTION HYVET ANBP-2 LIFE ACCORD VALUE ALLHAT I-PreserveCHARM-P DIG-PEF
ACCORD [Action to Control Cardiovascular Risk in Diabetes], second Australian National Blood Pressure trial [ANBP-2], ACTION [A Coronary disease Trial Investigating Outcome with Nifedipine], Losartan Intervention for Endpoint reduction in hypertension [LIFE], VALUE [Valsartan Antihypertensive Long-term Use Evaluation], Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT], and Hypertension in the Very Elderly Trial [HYVET]) and heart failure– preserved ejection fraction (HF-PEF) trials (DIG-PEF, CHARM-Preserved, and I-PRESERVE); CV, cardiovascular; HFpEF, Heart failure with preserved ejection fraction
Campbell RT et al. J Am Coll Cardiol 2012;60:2349–56.
Tử vong ở bệnh nhân HFpEF sv HFrEF
Tỉ lệ tử vong ở bệnh nhân HFpEF thấp hơn HFrEF
Observational
RCT
The overall mortality rate was consistently lower in the placebo arms of HFpEF trials (I-Preserve and CHARM-Preserve) versus HFrEF trials (CHARM-Added and CHARM- Alternative)2
A recent international, prospective, multi-ethnic cohort study has shown that mortality rate in HFpEF is lower than HFrEF (p=0.0013)1
120
115
19%
111
100
)
80
%
14%
I-Preserve (n=4133)
12%
60
CHARM-Preserve (n=3023)
( p u - w o
l l
CHARM-Added (n=2548)
o f
54
r a e y 2 g n i r u d e t a r y t i l
53
CHARM-Alternative (n=2028)
40
s r a e y t n e i t a p 0 0 0 1 r e p e t a R
a t r o M
20
0
I-Preserve CHARM-Preserve CHARM-Added CHARM-Alternative
HFpEF (n=574)
HFmrEF (n=256)
HFrEF (n=1209)
HFmrEF, Heart Failure with mid-range ejection fraction; HFpEF, Heart failure with preserved ejection fraction; HFrEF, Heart failure with reduced ejection fraction.
1. Lam CSP et al. Eur Heart J. 2018;39(20):1770-1780. 2. Campbell RT et al. J Am Coll Cardiol 2012;60:2349–56.
HFrEF trials HFpEF trials
Xu hướng nhập viện ở bệnh nhân suy tim EF bảo tồn qua nc quan sát
High rate of HF hospitalizations in HFpEF and HFrEF, however a higher rate of non-HF readmissions is observed among patients with HFpEF
HF and CV readmissions in patients with HFpEF1*
According to 5-year outcomes analysis of patients in the GWTG-HF registry, a lower rate of HF readmissions was observed in HFpEF than HFrEF2
100
84
82.2
80
)
%
60
10% readmitted within 30-days of hospital discharge
48.5
40.5
40
( e t a r t n e v E
20
0
37% readmitted within 1 year of hospital discharge
HFpEF (n=18299)
HFrEF (n=18398)
*Study cohort included 40239 patients from 220 hospital sites in the GWTG-HF registry between January 1, 2005, and December 30, 2011. Patients in the GWTG-HF registry were hospitalized for acute decompensated heart failure. HFrEF (EF<40%); HFbEF (40%≤EF< 50%); HFpEF (EF ≥50%). GWTG-HF, Get With The Guidelines-Heart Failure; HFpEF, heart failure with preserved ejection fraction.
1. Cheng RK et al. Am. Heart J. 2014;168, 721–730; 2. Shah KS et al. J Am Coll Cardiol. 2017;70(20):2476-2486
All-cause readmissions HF readmissions
Điều trị HFpEF chưa xác định ?
4
Mục tiêu điều trị
Current management and unmet treatment needs
HFpEF
Situation
HFpEF patients areoften: • Elderly • Living with co-morbidities (e.g. hypertension, diabetes) • Highly symptomaticand have poor QoL
• Management of co-morbidities • Alleviate symptoms and improve well-being
Goals
Treatment
• Screen for comorbidities and treat to improve symptoms if present • Diuretics for congestion to alleviate symptoms and signs
HFpEF=Heart failure with preserved ejection fraction; QoL=Quality of life
Ponikowski P et al. Eur Heart J 2016;37(27):2129–200
Hướng dẫn ACC/AHA/HFSA về HFpEF
Nhưng…....
HFpE F
No treatment has yet been shown, convincingly, to reduce morbidity or mortality in patients with HFpEF or HFmrEF.1
HF=Heart failure; HFmrEF=Heart failure with mid-range ejection fraction; HFpEF=Heart failure with preserved ejection fraction
1. Ponikowski P et al. Eur Heart J 2016;37(27):2129–200
Tất cả nghiên cứu về HFpEF không giảm kết cục lâm sàng
CHARM-Preserved
PEP-CHF
I-PRESERVE
TOPCAT
21
Cleland JGF,et al. Eur Heart J. 2006;27:2338-2345; Massie BM, et al. N Engl J Med.2008;359:2456-67; Yusuf S, et al. Lancet.2003;363:777-781
Kết quả nghiên cứu TOPCAT theo vùng địa lý Mild benefit of spironolactone in HFpEF
Chúng ta sẽ có một điều trị hiệu quả cho HFpEF ?
PARAMOUNT: thử nghiệm pha 2 duy nhất về HFpEF có kết quả dương tính
Improvement in NT-proBNP
Improvement in NYHA Class
Improvement in Left Atrial Size
NTproBNP (pg/ml)
Percent of Patients
Change in Left Atrial Volume (ml)
P = 0.05
12 Weeks
36 Weeks
P = 0.11
862 (733,1012)
2
1000
835 (710, 981)
1
900
0
Valsartan
800
-1
-2
700
-3
600
LCZ696
-4
p = 0.063
-5
500
100 90 80 70 60 50 40 30 20 10 0
P = 0.18
P = 0.003
LCZ696 Valsartan
LCZ696 Valsartan
-6
400
LCZ696/Valsartan: 0.77 (0.64, 0.92) P = 0.005
Week 36
Week 12
783 (670,914)
605 (512, 714)
300
200
LCZ696 Valsartan
0
10
5
Worsened Unchanged Improved
12 Weeks Post Randomization
Solomon et al. Lancet 2012
Kết luận
Heart failure with preserved ejection fraction (HFpEF) is a condition of multiple etiologies and presentations with a prevalence up to 50% and signs and symptoms similar to HFrEF
Compared to HFrEF, patients with HFpEF tend to be older and more likely to be women with a history of hypertension. Obesity, CAD, diabetes mellitus, AF, and hyperlipidemia are also highly prevalent in HFpEF
HFpEF patients suffer from a high mortality rate compared to age-matched general population, mainly driven by high CV mortality, however it is lower than HFrEF with a greater proportion of non-CV deaths
High rate of HF hospitalizations in HFpEF and HFrEF, however a higher rate of non-HF readmissions is observed among patients with HFpEF. With the high burden and resource utilization of recurrent hospitalizations, analysis taking into account the recurrent events helps in identifying better treatment targets
AF, atrial fibrillation; CAD, coronary artery disease; CV, cardiovascular; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; LV, left ventricular.
