2024 CHF TW

Acta Cardiol Sin 2024;40:148-171
Guidelines doi: 10.6515/ACS.202403_40(2).20240206A
2024 Guidelines of the Taiwan Society of

Cardiology for the Diagnosis and Treatment of
Heart Failure with Preserved Ejection Fraction
Yi-Heng Li,1# Chun-Chieh Wang,2 Chung-Lieh Hung,3,4 Yen-Wen Wu,5,6,7 Chih-Hsin Hsu,1 Yi-Liang Tsou,8
Chao-Hung Wang,8 Cho-Kai Wu,9 Po-Lin Lin,10 Hung-Yu Chang,5,11 Shih-Hsien Sung,12,13 Zheng-Wei Chen,9,14
Jyh-Ming Jimmy Juang,9 Tzung-Dau Wang9 and Wen-Jone Chen9,15#
on behalf of the Taiwan Society of Cardiology
Heart failure with preserved ejection fraction (HFpEF) is a multi-organ systemic syndrome that involves cardiac and
extra-cardiac pathophysiological abnormalities. Its growing prevalence causes a major public concern worldwide.
HFpEF is usually associated with multiple comorbidities, and non-cardiovascular death is common in patients with
HFpEF. In Asia, patients with HFpEF has a younger age, higher prevalence of diabetes and chronic kidney disease
than Western countries. A 2-step diagnostic algorithm is recommended in this guideline. In the first step, the
diagnosis of HFpEF can be made if patients have symptoms and/or signs of heart failure, left ventricular ejection
fraction ³ 50%, increased natriuretic peptide, and objective evidence of left atrial or left ventricular abnormalities
or raised left ventricular filling pressure. If diagnosis is still uncertain, invasive or noninvasive stress test can be
performed in the second step. Comorbidities need to be controlled in HFpEF. Weight reduction for obesity and
supervised exercise training are recommended for HFpEF. For pharmacological therapy, diuretic is used to relieve
congestion and sodium-glucose cotransporter 2 inhibitor, empagliflozin or dapagliflozin, is recommended to improve
prognosis of HFpEF. The research on HFpEF is advancing at a rapid pace. It is expected that newer modalities for
diagnosis and management of HFpEF could appear in the near future.
Key Words: Guideline · Heart failure with preserved ejection fraction · Taiwan
Received: January 8, 2024 Accepted: February 6, 2024

1
Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan;
2
Division of Cardiology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital and School of Medicine, Chang Gung
University, Taoyuan; 3Institute of Biomedical Sciences, MacKay Medical College, New Taipei City; 4Division of Cardiology, Department of
Internal Medicine, MacKay Memorial Hospital, Taipei; 5School of Medicine, National Yang Ming Chiao Tung University, Taipei; 6Department of
Nuclear Medicine and Cardiovascular Medical Center (Cardiology), Far Eastern Memorial Hospital, New Taipei City; 7Graduate Institute of
Medicine, Yuan Ze University, Taoyuan; 8Heart Failure Research Center, Division of Cardiology, Department of Internal Medicine, Keelung
Chang Gung Memorial Hospital, Keelung, and School of Medicine, Chang Gung University, Taoyuan; 9Division of Cardiology, Department
of Internal Medicine, National Taiwan University College of Medicine and Hospital, Taipei; 10Division of Cardiology, Department of Internal
Medicine, Hsinchu MacKay Memorial Hospital, Hsinchu; 11Heart Center, Cheng Hsin General Hospital; 12Institute of Emergency and Critical
Care Medicine, National Yang Ming Chiao Tung University; 13Department of Medicine, Taipei Veterans General Hospital, Taipei; 14Department
of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin; 15Division of Cardiology, Department of Internal Medicine,
Min Sheng General Hospital, Taoyuan, Taiwan.
Corresponding author: Dr. Yi-Heng Li, Department of Internal Medicine, National Cheng Kung University Hospital, No. 138, Sheng Li Road,
Tainan, Taiwan. Tel: 886-6-235-3535 ext. 2389; Fax: 886-6-275-3834; E-mail: [email protected]
* All authors contributed equally to this work.
#
Dr. Wen-Jone Chen and Dr. Yi-Heng Li contributed equally as corresponding authors.
Acta Cardiol Sin 2024;40:148-171 148

Taiwan Guideline for Heart Failure with Preserved Ejection Fraction
Abbreviations INTRODUCTION
ACEI Angiotensin converting enzyme inhibitor
AF Atrial fibrillation
AHA GWTG-HF American Heart Association Get With The Heart failure with preserved ejection fraction (HFpEF)
Guideline-HF is diagnosed as those with symptoms and/or signs of
ARB Angiotensin receptor blocker
ARNI Angiotensin receptor-neprilysin inhibitor heart failure (HF), left ventricular (LV) ejection fraction
ATTR-CM Transthyretin amyloid cardiomyopathy (EF) of 50% or greater, elevated natriuretic peptide and
BMI Body mass index cardiac structural change or diastolic dysfunction.1,2 The
BNP B-type natriuretic peptide
CAD Coronary artery disease growing trend of HFpEF causes public health problem
CHARM-Preserved Candesartan in Heart Failure: Assessment worldwide, including in Asia.3,4 For many years, how to
of Reduction in Mortality and Morbidity-
Preserved make a correct diagnosis of HFpEF is still controversial.
CKD Chronic kidney disease There is a consensus that the diagnosis of HFpEF needs
COR Class of recommendation
CT Computed tomography evidence of elevated cardiac filling pressure and natri-
CV Cardiovascular uretic peptide with the presence of structural heart dis-
CXR Chest X-ray ease.5 Traditionally, management of comorbidities and
DKA Diabetic ketoacidosis
DM Diabetes mellitus relief of congestion with diuretics are the main thera-
ECG Electrocardiography pies for HFpEF. In recent years, a number of randomized
EF Ejection fraction
eGFR Estimated glomerular filtration rate clinical trials demonstrated that some medical therapies
GLP1RA Glucagon-like peptide-1 receptor agonists could change the natural course of HFpEF and effectively
HCM Hypertrophic cardiomyopathy
HF Heart failure reduce the risk of HF hospitalization. The Taiwan Society
HFmrEF HF with mildly reduced ejection fraction of Cardiology published HF Guideline in 2012 and its fo-
HFnEF HF with normal EF cus update in 2019.1,6 Since there have been new scien-
HFpEF Heart failure with preserved ejection
fraction tific evidences regarding the epidemiology, diagnosis
HFrEF HF with reduced ejection fraction and treatment of HFpEF after 2019, the HF committee
I-Preserve Irbesartan in Heart Failure with Preserved
Ejection Fraction Study of Taiwan Society of Cardiology decided to create a new
LA Left atrial HF guideline specifically for HFpEF.
LOE Level of evidence
LV Left ventricular The guideline writers were invited mainly from the
LVEF Left ventricular ejection fraction Taiwan Society of Cardiology HF committee which con-
MI Myocardial infarction
MRA Mineralocorticoid receptor antagonist
sisted of 15 members nominated by the President of Tai-
MRI Magnetic resonance imaging wan Society of Cardiology and endorsed by the Society’s
NT-proBNP N-terminal proB-type natriuretic peptide board meeting in 2022. Three writer meetings were held
PARAGON-HF Prospective Comparison of ARNI with
ARB Global Outcomes in HF with on April 16, 2023 in Taipei, June 17, 2023 in Taichung
Preserved Ejection Fraction and September 24, 2023 in Kaohsiung. During the meet-
PCV13 13-valent pneumococcal conjugate vaccine
PCWP Pulmonary capillary wedge pressure ings, the panel decided the main contents of the HFpEF
PET Positron emission tomography guideline, including definition, epidemiology, pathophy-
PPV23 23-valent pneumococcal polysaccharide
vaccine
siology, diagnosis, treatment and future perspective.
RATE-AF Rate Control Therapy Evaluation in The writers assigned to one of these sections were re-
Permanent Atrial Fibrillation sponsible for collecting available evidence, reviewing its
REHAB-HF Rehabilitation Therapy in Older Acute
Heart Failure Patients scientific intensity and making proper recommendations.
RV Right ventricular Consensus about guideline recommendations was achi-
SGLT2 Sodium-glucose cotransporter 2
STRONG-HF Safety, Tolerability and Efficacy of Up- eved by all writers during the meetings. Similar to the
titration of Guideline-directed Medical recently published guidelines from the Taiwan Society of
Therapies for Acute Heart Failure
TOPCAT Treatment of Preserved Cardiac Function Cardiology,7 this guideline adopted class of recommen-
Heart Failure With an Aldosterone dation (COR) to indicate whether a recommendation is
Antagonist useful or harmful and level of evidence (LOE) to describe
TR Tricuspid regurgitation
TTE Transthoracic echocardiography the strength of scientific evidence about the recommen-
US United States dations. In COR, Class I recommendations indicate they
149 Acta Cardiol Sin 2024;40:148-171

Yi-Heng Li et al.
are useful and beneficial for the patients. Class IIa recom- that the clinical syndrome is primarily due to diastolic
mendations indicate that the evidence favors the recom- dysfunction. These criteria include: (1) HF symptoms
mendations and could be used for the patients. Class IIb and/or signs. Patients with HFpEF typically present with
recommendations are those may be considered but the exertional dyspnea, fatigue, exercise intolerance, and
scientific strength is less well established. Class III recom- fluid retention leading to peripheral edema. Elevated
mendations are the treatment that is unnecessary or jugular venous pressure, pulmonary rales, and periph-
harmful. There are three levels for LOE. LOE A recom- eral edema often accompany these symptoms. (2) Evi-
mendations are supported by multiple randomized clini- dence of structural heart disease. HFpEF is frequently
cal trials or meta-analyses of randomized clinical trials. associated with underlying structural heart abnormali-
LOE B recommendations are from only one randomized ties, including LV hypertrophy, increased left atrial (LA)
clinical trial or non-randomized observational studies. size, and diastolic dysfunction. Echocardiography is com-
LOE C recommendations are from case series, case re- monly used to assess these structural abnormalities and
ports or consensus of expert opinions. to measure the EF. (3) Evidence of diastolic dysfunction.
Diastolic dysfunction refers to abnormalities in the filling
of the ventricles during diastole. In HFpEF, impaired re-
DEFINITION laxation, increased ventricular stiffness, and abnormal
filling pressure are commonly observed. These abnor-
HF is a complex clinical syndrome that results from malities can be assessed using Doppler echocardiogra-
impaired cardiac function, leading to an inability of the phy which provides information on transmitral flow ve-
heart to meet the body’s metabolic demand adequately.8 locities, pulmonary venous flow, and tissue Doppler im-
Conventionally, HF can be categorized into three main aging. (4) Additional diagnostic tests. In some cases, ad-
subtypes based on left ventricular ejection fraction (LVEF), ditional tests may be required to establish the diagnosis
a measure of the heart’s pumping efficiency. These sub- of HFpEF and exclude other causes of patients’ symptoms.
types are HF with reduced ejection fraction (HFrEF), HF These tests may include cardiopulmonary exercise test-
with mildly reduced ejection fraction (HFmrEF), and ing, cardiac catheterization, magnetic resonance imag-
HFpEF (Table 1).2,5,9 An expert consensus from the Taiwan ing (MRI), or nuclear imaging studies.
Society of Cardiology suggests to reclassify those pa-
tients with LVEF ³ 60% as HF with normal EF (HFnEF).10 Recommendation
HFpEF, previously known as diastolic HF, refers to a clini- · HFpEF is defined as the presence of HF symptoms
cal syndrome in which patients have signs and symp- and/or signs with LVEF ³ 50%, structural heart disease
toms of HF but have a relatively normal EF. The LVEF in and diastolic dysfunction. (COR I, LOE A)
HFpEF is typically greater than or equal to 50%.2,5,9 It is
important to note that the definition of HFpEF is not
solely based on the EF but includes additional clinical EPIDEMIOLOGY
criteria. The EF alone is not sufficient to establish the di-
agnosis. Additional criteria are necessary to differenti- Prevalence and incidence of HFpEF
ate HFpEF from other causes of dyspnea and to ensure In Taiwan, the prevalence of HF may be as high as
Table 1. Definition of heart failure
Type of HF HFpEF HFmrEF HFrEF
LVEF ³ 50% 41-49% £ 40%
· Symptoms/signs · Symptoms/signs · Symptoms/signs
· Evidence of structural and/or functional cardiac abnormalities and
LV diastolic dysfunction
Natriuretic peptide is usually elevated in HF.
HF, heart failure; HFmrEF, heart failure with mildly reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction;
HFrEF, heart failure with reduced ejection fraction; LV, left ventricular; LVEF, left ventricular ejection fraction.
* Modified from reference 9.
Acta Cardiol Sin 2024;40:148-171 150

6%.11 A recent analysis using HF hospitalization as an ad- was found.14 The Olmsted County cohort from the US
judicated event showed that the HF prevalence in Tai- showed that 52.5% of patients with incident HF were
wan is estimated to be 1.63 to 1.99% from 2020 to HFpEF.15 Overall, the prevalence of HFpEF was increas-
2025.12 Overall, the projected HF burden in Taiwan will ing, but HFrEF prevalence seemed to be stable or declin-
resemble the findings from the United States (US) with an ing.3,16,17 For incidence of HFpEF, the Olmsted County
estimated tripled HF prevalence in 2050.12 Similar to the cohort from the US showed that the age- and sex-ad-
global trend, the HF incidence is decreasing in Taiwan justed incidence of HF declined substantially with a 45%
with an estimated incidence of 2.44 in 2001 to 2.19 per decrease in HFrEF compared with 28% in HFpEF.15 But
1000 person-years in 2016.12,13 However, the age-strati- more recent data from the Framingham Heart Study and
fied HF incidence is different with 10-20% decrease in Cardiovascular Health Study, a declining incidence for
older individuals (³ 55 years), but approximately 4% in- HFrEF and increasing incidence for HFpEF was oberved.18
crease among younger population (< 44 years).12,13 Table 2 shows the prevalence and incidence of HFpEF in
According to the registry data from Western coun- different registries or population-based studies.
tries, near half of the patients with HF have HFpEF. In
patients admitted due to HF between 2005 and 2009 in Recommendation
the American Heart Association Get With The Guideline- · There is an increasing prevalence of HFpEF, but the
HF (AHA GWTG-HF) registry, a prevalence of 46% HFpEF prevalence of HFrEF is stable or declining. (COR I, LOE A)
Table 2. Relative distribution of HFpEF in cross-sectional and longitudinal observational studies

Prevalence of HFpEF HFrEF HFmrEF HFpEF
Study name
European Society of Cardiology Long-Term Registry 60% 24% 16%
Swedish HF Registry 56% 21% 23%
Multicentre nationwide Italian Network (Spain) 32% 16% 52%
† †
UK-HEART Study NA NA 31%
Cardiovascular Health Study NA NA *22%*
ADHERE Inpatient Cohort NA NA 50%
OPTIMIZE-HF Registry (United States) 49% 17% 24%
‡ ‡
Framingham Heart Study (1981-2008) NA NA 43%
Get With The Guidelines-HF (GWTG-HF) 39% 14% 47%
Strong Heart Study (American Indians) NA NA *53%*
# #
ADHERE Inpatient Cohort NA NA 50%
Global Congestive Heart Failure Registry 54% 21% 24%
‡ ‡
Pooled Community Cohorts (Framingham Heart Study, Cardiovascular Health Study, NA NA 48%
Prevention of Renal and Vascular End-Stage Disease, Multi-Ethnic Study of Atherosclerosis)
Multicenter Inpatient Cohort (Japan, 2013 to 2014) 36% 21% 43%
Asian-HF Registry 81% NA 19%
China Hypertension Survey (China, 2012-2015) 40% 23% 37%
Incidence of HFpEF HFrEF HFpEF

Study name
PREVEND Prevention of Renal and Vascular End-Stage Disease (Dutch Community) 66% (< 40%) 34% (³ 50%)
Olmsted County, Minnesota (2008-2010) 48% (< 50%) 52% (³ 50%)
Framingham Heart Study/Cardiovascular Health Study (³ 60 years, 2000-2009) 45% (< 50%) 55% (³ 50%)
Longitudinal American Community-Based Cohort 52% 48%
Among Canadian Inpatients (Ontario, 1999-2001) 56% 31%
Dutch Community Based Cohort 66% 34%
Abbreviations are the same as the Table 1. NA, not applicable.
† ‡ #
LVEF cutoffs: * LVEF ³ 55%, LVEF ³ 50%, LVEF ³ 45%, LVEF ³ 40%.
151 Acta Cardiol Sin 2024;40:148-171

Yi-Heng Li et al.
Risk factor, comorbidity and phenotype of HFpEF HF hospitalization rates were increasing over time and
Compared with HFrEF, patients with HFpEF tend to largely driven by HFpEF events.38,39 A greater proportion
be older, predominantly female, and are associated with of HFrEF hospitalization was attributed to the male sex,
multiple comorbidities.16 Older age is strongly associated while a greater proportion of HFpEF hospitalization oc-
with HFpEF. On the contrary, the risk factors, such as male curred in the female population. Hospitalization for car-
sex, previous myocardial infarction (MI), LV hypertrophy, diovascular (CV) causes appeared to be higher in indi-
and left bundle branch block, are more commonly associ- viduals with HFrEF. However, non-CV hospitalization
ated with HFrEF rather than HFpEF.19 Lifestyle factor may was comparable between HFrEF and HFpEF indicating a
also play a role as a risk of HFpEF. Previous study showed higher impact of non-CV related comorbidities on HFpEF
that individuals with more leisure-time physical activity hospitalization. 40 Albeit the total hospitalization rate
had a lower risk of HFpEF than those with no leisure-time among HF patients was similar irrespective of LVEF, the
physical activity; whereas no such association was ob- short-term hospitalization rate within 1 year after discharge
served for the risk of HFrEF.20 Comorbidities are common was still higher in patients with HFrEF than HFpEF.41,42
in patients with HFpEF, including hypertension, diabetes Overall, patients with HF have higher 30-day readmis-
mellitus (DM), chronic kidney disease (CKD), coronary ar- sion rate after discharge compared with patients admitted
tery disease (CAD), atrial fibrillation (AF), obesity, ob- with other diagnoses and HF remains the number one
structive sleep apnea, and metabolically associated fatty cause of hospitalization in the older population.43
liver disease.21-29 Because HFpEF is highly heterogeneous In Taiwan, the mortality of HF was estimated to be
with multiple different comorbidities, several analyses 22.5%, 33.9%, and 42.8% at 1, 2, and 3-year follow-up, re-
have been performed in clustering patients with HFpEF spectively. A longer duration study showed the mortality
into different phenotypes. Although there were different was 62.1%, 69.6%, and 75.5% at 6, 8, and 10-year follow-
methods to classify the patients, several phenotypes of up.12,13 Another 16-year analysis in Taiwan revealed an
HFpEF are commonly identified, including diabetes and in-hospital mortality rate of 4.12% in patients with newly
obesity, AF and CKD, young patients with milder HF symp- diagnosed HF and the mortality after discharge was esti-
toms and fewer comorbidities, men with AF, and elderly mated to be 38.5%, 52.2%, 62.1%, 69.6%, and 75.5% at 2, 4,
frail women with AF.30 The findings of diverse phenotypes 6, 8, and 10-year follow-up, respectively.12,44 In general, pa-
in patients with HFpEF increase the potential for pheno- tients with HFpEF tended to have better overall survival
type-specific treatment in such populations.31-33 Com- than those with HFrEF.14,16 In the Asian-HF registry, the
pared to the findings from Western countries, the comor- crude annual all-cause mortality rate was higher in patients
bidities of HFpEF in Asia demonstrated a younger age, with HFrEF than in those with HFpEF.45 Importantly, most of
lower prevalence of CAD, AF, and obesity, but a higher the causes of death were CV death among patients with
prevalence of diabetes and CKD.34,35 One unique HFpEF HFrEF.46 In contrast, non-CV death was more frequent in
phenotype in Asia is patients with lean diabetes.35 The patients with HFpEF. In Asia, the risk of CV death was
clinical features of HFpEF in Taiwan were similar to those slightly higher in patients with HFrEF than in those with
reported from the Asian studies.36,37 HFpEF, whereas non-CV death was more frequent in pa-
tients with HFpEF than HFrEF at 1-year follow-up.45
Recommendation
· HFpEF patients tend to be older, predominantly fe- Recommendation
male, and are associated with multiple comorbidities. · Patients with HFpEF have a better survival than HFrEF
(COR I, LOE A) and non-CV death is more frequent in patients with
· The Asian HFpEF patients tend to be younger and have HFpEF. (COR I, LOE A)
higher prevalence of diabetes and CKD than Western
countries. (COR I, LOE A) Cardiomyopathy
HFpEF can be presented in most patients with ob-
Outcome of HFpEF structive hypertrophic cardiomyopathy (HCM) and ap-
Several studies from the US showed that the secular proximately 10% of patients with nonobstructive HCM.47
Acta Cardiol Sin 2024;40:148-171 152

HCM is an important genetic heart muscle disease, how- are multiple and cross-linked, LV diastolic dysfunction
ever, its prevalence in the general population has not forms a major basis of the clinical syndrome of HFpEF.53-58
yet been completely resolved. Most data indicate that However, it does not fully represent the whole patho-
the occurrence of HCM is approximately 1 in 500 individ- physiological abnormalities of HFpEF.58 Diastolic dysfunc-
uals. However, recent studies suggest that the prevalence tion results from decreased LV chamber distensibility
of HCM may be more common than previously estimated. and causes increased diastolic pressure at any given LV
A timely diagnosis and treatment are crucial since the de- volume. Patients with HFpEF display an abnormal LV dia-
velopment of advanced HF in HCM portends a poor prog- stolic pressure-volume relationship that is shifted up
nosis.48,49 Infiltrative cardiomyopathy is a heterogeneous and to the left indicating an increase in passive chamber
group of disease and may present with HFpEF. Among stiffness. The primary factors affecting myocardial stiff-
them, transthyretin amyloid cardiomyopathy (ATTR-CM) ness include abnormalities in extracellular matrix, car-
is an under-recognized cause of HFpEF. In Taiwan, late- diomyocytes, matricellular proteins, calcium ion homeo-
onset hereditary ATTR amyloidosis with the A117S muta- stasis, myocardial energy supply, and increased fat con-
tion and polyneuropathy is often associated with heart tent in myocardium and pericardium.59-62 Patients with
involvement. Recent studies have suggested that 10-15% HFpEF display prolonged relaxation and inability to has-
of older adults with HF may have an unrecognized ATTR- ten relaxation as heart rate increases during exercise.63,64
CM. The associated carpal tunnel syndrome and lumbar Prolonged relaxation usually does not affect LV filling
spinal stenosis may raise clinical suspicion and early diag- when heart rate is normal at rest, but it significantly in-
nosis.50,51 Fabry disease is a X-linked inborn error of gly- creases LV filling pressure during exertion as cycle length
cosphingolipid metabolism due to alpha-galactosidase A shortens in tachycardia. In patients at early stage of
deficiency. Newborn screening identified a high frequ- HFpEF, LV filling pressure becomes markedly elevated
ency of Taiwanese male with Fabry disease (approximately only during exercise; however, at advanced stage of
1 in 1250) with 86% having the IVS4+919G>A mutation.52 HFpEF, LV filling pressure is elevated even at rest.65 In-
HFpEF is common in infiltrative cardiomyopathy. Irrespec- creased LV filling pressure during exertion in HFpEF di-
tive of the etiology, HF is a harbinger of poor outcomes of rectly correlated with heightened inspiratory drive,
cardiomyopathy. Disease-modifying therapies are avail- symptoms of dyspnea, alterations in gas exchange and
able for cardiac amyloidosis and Fabry disease and carry pulmonary ventilation, and reduction in aerobic capacity.
potential to improve outcomes. Elevation in LV filling pressures alters the Starling force
across the pulmonary capillaries, pushing water out of
Recommendation the vascular space into the interstitium. Over time, high
· HFpEF can be presented in most patients with hyper- LV filling pressure may promote vascular remodeling,
trophic or infiltrative cardiomyopathy. (COR I, LOE A) particularly in pulmonary veins.
LV systolic dysfunction
PATHOPHYSIOLOGY HFpEF is defined as HF with normal or nearly nor-
mal LVEF, but EF is only a rough estimate of LV contrac-
The pathophysiology of HFpEF involves multisystem tile function. Actually, LV systolic function is relatively
abnormalities with different mechanisms, including car- impaired in patients with HFpEF compared with the age-
diac dysfunction (left or right heart), vascular dysfunc- matched healthy controls.66 Impairment in myocardial
tion, peripheral tissue abnormality, or cardiomyopathy and chamber-level function is present at rest and becomes
(hypertrophic or infiltrative). more severe during exercise.66-68 This limits the ability of
the heart to increase stroke volume and substantially
Cardiac dysfunction impairs the cardiac output to meet the need in exercise.
In addition, LV systolic reserve deficits compromise dia-
LV diastolic dysfunction stolic reserve because the ability to enhance contractil-
Although the pathophysiological mechanisms of HFpEF ity plays a key role in determining the restoring force
153 Acta Cardiol Sin 2024;40:148-171

Yi-Heng Li et al.
that enhances early diastolic annular motion or recoil. patients. However, all these theories only partially ex-
plain the chronotropic incompetence in HFpEF.77,78
Left atrial dysfunction
As the LV diastolic filling pressure elevates intermit- Right ventricular dysfunction
tently over time in HFpEF, secondary remodeling and Right ventricular (RV) dysfunction leads to augmented
dysfunction develop in the LA. Preservation of LA func- right heart distention and elevated LV filling pressure.79
tion may be an important adaptation in HFpEF because Longstanding pulmonary hypertension in HFpEF eventu-
development of LA dysfunction is associated with worse ally causes RV dysfunction which is seen in 20%-35% of
exercise capacity, more profound pulmonary vascular patients with HFpEF. 80 However, this is not mediated
disease, and increased risk of death.69 LA remodeling purely by afterload mismatch. RV dysfunction was also
and dysfunction are common features in AF and HFpEF independently correlated with male sex and AF which
which are frequently coexisting conditions. Both condi- may influence RV function in a load-independent man-
tions also share several common comorbidities such as ner. Other potential contributing comorbidities include
hypertension, diabetes and obesity.17,25,70-72 HFpEF causes coronary disease and lung disease.81,82 The presence of
AF due to the structural and functional remodeling of the RV dysfunction is associated with increased morbidity
LA, while AF is also associated with LV myocardial fibro- and mortality of HFpEF.83,84
sis that contributes to LV diastolic dysfunction and HFpEF.
Vascular dysfunction
Coronary microvascular dysfunction
Coronary microvascular dysfunction is a common Abnormal systemic vascular function
phenomenon in patients with HFpEF and causes de- Peripheral vascular function is impaired in HFpEF
mand-supply mismatch. In the functional aspect, low patients. During exercise, macrovascular stiffness in-
coronary flow reserve in HFpEF causes impaired myocar- creases and can be reversed by inorganic nitrite.85,86 It
dial oxygen delivery so that myocardial ischemia and in- has been reported that the increase of adipocyte free
jury occur especially during exercise.73-75 Myocardial sys- fatty acid binding protein contributes to central arterial
tolic and diastolic reserves both decrease when the se- stiffness.87 In the microvascular level, endothelial dys-
verity of coronary microvascular dysfunction increases. function and inflammation lead to impaired flow-medi-
In the anatomic aspect, coronary microvascular rarefac- ated and NO-mediated vasodilation.65,88 Because of sys-
tion and myocardial fibrosis are noted in an autopsy temic vascular dysfunction, the arterial elastance, an es-
study of patients with HFpEF.76 Based on these evidence, timate of afterload, elevates more than the LV end-sys-
coronary microvascular dysfunction seems to be an- tolic elastance, an estimate of LV chamber performance,
other mechanism that contribute to HFpEF and may be during exertion and causes ventricular-arterial uncou-
a therapeutic target. pling. Abnormal ventricular-arterial coupling develops
even at low-level workload.65,89 Ventricular-arterial un-
Chronotropic incompetence coupling can be reflected by decreased carotid arterial
Exercise intolerance is partly related to lower peak strain and may serve as a prognostic indicator of HFpEF.90
heart rate achieved in HFpEF patients. Because increas-
ing heart rate is the major contributor of cardiac output Abnormal pulmonary vascular function
during exercise, impairment in heart rate reserve can Pulmonary hypertension is defined as mean pulmo-
lead to exertional intolerance. The mechanism of inabil- nary artery pressure > 20 mmHg.91 Pulmonary hyperten-
ity to increase heart rate in HFpEF patients is not fully sion and pulmonary vascular remodeling are present in
understood. Premature cessation of exercise due to ele- about 70%-80% of patients with HFpEF.92 Impaired pul-
vated LV filling pressure and beta-blocker use may ac- monary vascular function displays a unique pathophy-
count for lower maximal heart rate in some patients siology similar to RV dysfunction.79 In addition, even pa-
with HFpEF. Autonomic dysfunction and reduced cardiac tients with HFpEF have normal pulmonary vascular re-
beta-receptor response are also observed in some HFpEF sistance at rest, some of them may have inadequate pul-
Acta Cardiol Sin 2024;40:148-171 154

monary vasodilation in response to exercise.93 Cardio- tion, vascular dysfunction, peripheral tissue abnor-
pulmonary exercise testing may provide some diagnos- mality, and cardiomyopathy. (COR I, LOE A)
tic clues of abnormal pulmonary hemodynamic response · Correct diagnosis of hypertrophic or infiltrative car-
in HFpEF. Using stress echocardiography to non-inva- diomyopathy in patients presenting with HFpEF is im-
sively evaluate mean pulmonary artery pressure – car- portant. (COR I, LOE A)
diac output relationship, it was found that patients with
HFpEF and exercise-induced pulmonary hypertension
have worse exercise capacity, lower peak oxygen con- DIAGNOSIS
sumption and depressed RV systolic function.94 These
patients also had higher rates of composite outcomes of HF symptoms and signs
all-cause mortality or HF events.94 To identify symptoms and signs of HF is the begin-
ning step to diagnose HFpEF. The Framingham Diagnos-
Peripheral tissue abnormality tic Criteria describe the major symptoms or signs indi-
In addition to CV system, abnormalities in periph- cating the presence of HF (Table 4). The criteria are de-
eral tissue also contribute to the pathophysiology of rived from the information gathered during the Framing-
HFpEF. The oxygen diffusion and extraction in skeletal ham Heart Study.103 A HF diagnosis requires the presence
muscle are impaired in patients with HFpEF.69,95,96 Mito- of two major criteria or one major and two minor crite-
chondrial dysfunction, including content and structure ria. The major criteria include orthopnea or paroxysmal
abnormalities, in skeletal muscle leads to exercise intol- nocturnal dyspnea, jugular venous distension, hepato-
erance as well.97 The coexistence of obesity and sarco- jugular reflux, rales, S3 gallop rhythm, pulmonary edema,
penia, so called “sarcopenic obesity”, is quite often in and cardiomegaly. The minor criteria include exertional
patients with HFpEF and is associated with adverse clini- dyspnea, nighttime cough, ankle edema, tachycardia with
cal outcomes.98 a heart rate surpassing 120 beats per minute, hepato-
megaly, and pleural effusion. Dyspnea or ankle edema
Hypertrophic/infiltrative cardiomyopathy are common first presentations of HFpEF. However, it is
HCM and infiltrative cardiomyopathy are HFpEF necessary to make a differential diagnosis and consider
mimics which have distinct pathophysiology and clinical other causes before making the diagnosis of HF. For
outcome. Both of them can present with classic symp- dyspnea, the differential diagnosis includes cardiac dis-
toms of HFpEF. Careful history taking, physical examina- eases other than HF, pulmonary diseases and other causes,
tion, and echocardiography are helpful to identify car- such as anemia, neuromuscular disease and anxiety. For
diac amyloidosis, cardiac sarcoidosis, hemochromatosis, edema, renal failure, lymphedema, liver cirrhosis, and
and Fabry disease. In addition, some gene mutations drug-related ankle edema (for example, dihydropyridine
have been reported to cause cardiomyopathy, such as calcium-channel blockers) should be ruled out.
MYH7 and MYBPC3 gene mutations for HCM, transthy-
retin gene mutation for cardiac amyloidosis, and GLA History and physical examination
gene mutation for Fabry disease.99 Diagnostic tests for Initial assessment of patient with suspected HFpEF
these HFpEF mimics are crucial because there are spe- includes history and physical examination. An important
cific treatments once the diagnosis is made.100 part of the history and physical evaluation is the scru-
In summary, HFpEF is a common form of HF in the tiny of clinical congestion which is the manifestation ari-
elderly, especially in women, and those with multiple sing from heightened cardiac filling pressures. Address-
comorbidities.101,102 Table 3 summarizes the pathophy- ing congestion is pivotal for adjusting medications and is
siology of HFpEF that maybe involved in aging, female, intertwined with the quality of life and prognosis of HF
and different comorbidities. patients. Various methods exist to evaluate clinical con-
gestion, encompassing the presence of jugular venous
Recommendation distention, orthopnea, bendopnea, a square-wave re-
· Pathophysiology of HFpEF involves cardiac dysfunc- sponse to the Valsalva maneuver, and leg edema.104-106
155 Acta Cardiol Sin 2024;40:148-171

Yi-Heng Li et al.
Table 3. Pathophysiology of HFpEF involved in aging, female, and different comorbidities

Common comorbidities in HFpEF Involved pathophysiology
General
Aging LV diastolic dysfunction
Chronotropic incompetence
Systemic vascular dysfunction
Peripheral tissue abnormality
Female LV diastolic dysfunction
Pulmonary vascular dysfunction
Cardiovascular
Atrial fibrillation LV diastolic dysfunction
LA dysfunction
Hypertension LV diastolic dysfunction
LA dysfunction
Coronary artery disease LV diastolic dysfunction
Respiratory
Chronic obstructive pulmonary disease LV diastolic dysfunction
RV dysfunction
Sleep apnea syndrome Pulmonary vascular dysfunction
Metabolic
Diabetes mellitus LV diastolic dysfunction
Chronotropic incompetence
Obesity LV diastolic dysfunction
Nephrogenic
Chronic kidney disease LV diastolic dysfunction
HFpEF, heart failure with preserved ejection fraction; LA, left atrial; LV, left ventricular; RV, right ventricular.
Table 4. The Framingham diagnostic criteria of heart failure

Major Criteria Minor criteria
· Acute pulmonary edema · Ankle edema
· Cardiomegaly · Dyspnea on exertion
· Hepatojugular reflux · Hepatomegaly
· Neck vein distention · Nocturnal cough
· Paroxysmal nocturnal dyspnea or orthopnea · Pleural effusion
· Pulmonary rales · Tachycardia (heart rate greater than 120 beats per minute)
· Third heart sound (S3 gallop)
* Modified from reference 103. Diagnosis of heart failure requires the presence of two major criteria or one major and two minor
criteria.
Acta Cardiol Sin 2024;40:148-171 156

History and physical examination also help to identify ticularly when the cause of dyspnea remains uncertain
the potential causes of clinical deterioration in stable and physical examination yields inconclusive results.
HF, such as myocardial ischemia, pulmonary emboli, or Normal BNP and NT-proBNP levels aid in excluding the
systemic infection. History is important in identification diagnosis of HF, however, the natriuretic peptide levels
of inherited cardiomyopathies through familial history are usually not increased in HF patients with obesity and
or other specific conditions such as amyloid heart dis- diminish their diagnostic accuracy.110,111 Elevated levels
ease. Body weight should be evaluated because the se- of natriuretic peptide possess a strong positive predic-
verity of obesity is another important issue in HFpEF. tive value for HFpEF diagnosis. But it is noteworthy that
both BNP and NT-proBNP levels can rise in individuals
Laboratory test with a range of noncardiac conditions.112,113 The normal
Electrocardiography (ECG) is a routine examination levels of natriuretic peptide can be considered as a
for suspected HFpEF because the data of rhythm, heart first-line tool to exclude the diagnosis of HF. To avoid
rate, QRS morphology/duration provide vital informa- overdiagnosis, we suggest NT-proBNP > 300 pg/ mL or
tion of the potential underlying causes and prognosis of BNP > 100 pg/mL as the cut off values to diagnose HF in
HFpEF. Chest X-ray (CXR) is another valuable initial diag- sinus rhythm and NT-proBNP > 600 pg/mL or BNP > 150
nostic tool. It enables the evaluation of cardiac size, pul- pg/mL for AF. In Taiwan, other biomarkers including
monary congestion, as well as pleural effusion. Addi- galectin-3 and matrix metalloproteinase-2 were re-
tionally, it has the potential to unveil alternative pulmo- ported to be significantly associated with global cardiac
nary causes of the patient’s symptoms.107 Initial blood fibrosis in HFpEF patients.114 Connective tissue growth
examination include a complete blood count, electro- factor was documented to be associated with the pre-
lytes, urea nitrogen, creatinine, glucose, fasting lipid sence of HFpEF.115 Serum CA-125 was also mentioned to
profile, and liver function test. Other studies, including serve as a novel biomarker for HFpEF in women.116
iron profile (serum iron, ferritin, transferrin saturation)
and thyroid-stimulating hormone level, may be neces- Recommendations
sary to find coexisting conditions that are contributors · NT-proBNP or BNP should be measured in patients
or confounders of patients’ symptoms. with suspected HFpEF. (COR I, LOE A)
· HF should be considered when NT-proBNP > 300 pg/
Recommendations mL or BNP > 100 pg/mL in sinus rhythm and NT-proBNP
· A thorough history and physical examination should > 600 pg/mL or BNP > 150 pg/mL for AF. (COR I, LOE A)
be performed to search for HF symptoms/signs. (COR
I, LOE C) Cardiac imaging
· Initial evaluation should include 12-lead ECG and CXR. Cardiac imaging plays a pivotal role in the assessment
(COR I, LOE C) of individuals with suspected HFpEF. Transthoracic echo-
· Initial blood examination includes complete blood cardiography (TTE) stands as the most valuable initial di-
count, renal function, electrolytes, lipid profile and agnostic imaging tool. It determines LVEF which is the
liver function test. (COR I, LOE C) main criterion to differentiate HFrEF and HFpEF. TTE pro-
vides in-depth insights into cardiac structure and func-
HF biomarker tion. It identifies abnormalities within the myocardium,
Natriuretic peptide assay, including B-type natriuretic heart valves, and pericardium and the information could
peptide (BNP) or N-terminal proB-type natriuretic pep- offer diagnostic value for HFpEF.117-119 TTE evaluation en-
tide (NT-proBNP), is commonly used to confirm the pre- compasses RV dimension and function, atrial size, and
sence and severity of HFpEF. Generally, the levels of BNP comprehensive valve analysis, addressing both anatomi-
and NT-proBNP are comparable, rendering either one is cal and flow-related abnormalities. Diastolic function
suitable for clinical use.108,109 When evaluating dyspnea with estimated LV filling and LA pressures are also cov-
of potentially cardiac origin, measuring BNP and NT- ered. Furthermore, indices reflecting myocardial defor-
proBNP levels offers important diagnostic insight, par- mation, including global longitudinal strain, have the po-
157 Acta Cardiol Sin 2024;40:148-171

Yi-Heng Li et al.
tential to uncover subclinical LV systolic dysfunction.120-122 ties or raised LV filling pressure include: (1) LV mass in-
In addition to TTE, supplementary noninvasive imag- dex ³ 95 g/m2 in female and ³ 115 g/m2 in male, or (2)
ing tools can be helpful in evaluating cardiac structure LA volume index > 29 mL/m2 in sinus rhythm or > 40
and function. Cardiac MRI offers a precise and consis- mL/m2 in AF, or (3) average E/e¢ > 14, or (4) tricuspid re-
tently replicable evaluation of cardiac volumes, mass, and gurgitation (TR) velocity > 2.8 m/s.1,100,130
EF for both LV and RV.123 Cardiac MRI boasts exceptional If patients do not fulfill the four criteria of step-1 di-
anatomical resolution across all aspects of the heart and agnosis but HFpEF is still highly suspected or in any situ-
surrounding structures, without involving ionizing radia- ation that uncertainty persists after step-1 diagnosis,
tion. It is helpful in the diagnosis of HCM, cardiac amy- step-2 diagnosis with stress test could be considered
loidosis, cardiac sarcoidosis, and Fabry disease.51,124-126 (Figure 1). An exercise stress test combined with echo-
ECG-gated cardiac computed tomography (CT) similarly cardiographic evaluation of diastolic parameters should
delivers accurate assessments of ventricular size, EF, and be performed. A diagnosis of HFpEF could be made if an
abnormalities of wall motion.127 Radionuclide ventriculo- average E/e¢ ³ 15 or a TR velocity > 3.4 m/s are observed
graphy offers highly reproducible LVEF measurements, after exercise.131 If the results of stress echocardiogra-
but exposes patients to ionizing radiation.128 Positron phy is still questionable, an invasive hemodynamic mea-
emission tomography (PET) is a non-invasive imaging te- surement during rest and/or exercise could be consid-
chnique that provides information on myocardial meta- ered. The invasive hemodynamic measurement serves
bolism, perfusion, inflammation, and fibrosis.129 as the golden criteria for the diagnosis of HEpEF. If a pa-
tient has a resting LV end diastolic pressure ³ 16 mmHg
Recommendation or pulmonary capillary wedge pressure (PCWP) ³ 15
· Transthoracic echocardiography should be performed mmHg or an exercise PCWP ³ 25 mmHg, a definite diag-
for cardiac structural and functional evaluation in pa- nosis of HEpEF could be made.131
tients with suspected HFpEF. (COR I, LOE A)
· Other imaging tools, such as CT, MRI, radionuclide Recommendation
study or PET could be considered in patients with sus- · In step-1 diagnosis, HFpEF can be diagnosed if pati-
pected HFpEF. (COR I, LOE C) ents have symptoms and/or signs of HF, LVEF ³ 50%,
increased NT-proBNP or BNP, and objective evidence
Diagnostic algorithm of HFpEF of LA or LV abnormalities or raised LV filling pressure.
In this guideline, we proposed a 2-step diagnostic (COR I, LOE A)
algorithm for HFpEF. When patients have HF symptoms · Step-2 diagnosis using invasive or noninvasive stress
and signs fulfilling the criteria of Framingham Diagnostic test can be performed if HFpEF diagnosis is question-
Criteria and HFpEF is suspected, step-1 work up should able. (COR I, LOE C)
be started (Figure 1). NT-proBNP/BNP should be checked.
The presence of cardiac structural or functional abnor-
malities should be evaluated with TTE. The structural TREATMENT
abnormalities encompass an enlargement in LA size
and/or volume or an increase in LV mass. The functional The major goals of treatment for patients with HFpEF
abnormalities indicate the presence of increased LV fill- are to reduce symptoms, improve functional status, and
ing pressure. In step-1 diagnosis, the patients should ful- lower the risk of hospitalization for HF. Specific treatment
fill all the following four criteria to make a diagnosis of of cardiomyopathy is beyond the scope of this guideline.
HFpEF: (1) symptoms and/or signs of HF, (2) LVEF ³ 50%,
(3) increased natriuretic peptide (NT-proBNP > 300 pg/ Non-pharmacological treatment
mL or BNP > 100 pg/mL in sinus rhythm and NT-proBNP
> 600 pg/mL or BNP > 150 pg/mL in AF), (4) objective Weight reduction
evidence of LA or LV abnormalities or raised LV filling Obesity, especially the central obesity, is associated
pressure. The objective evidence of LA or LV abnormali- with a higher incidence of HF and all-cause mortality.132
Acta Cardiol Sin 2024;40:148-171 158

Figure 1. A 2-step diagnostic algorithm of HFpEF. AF, atrial fibrillation; BNP, B-type natriuretic peptide; CXR, chest X-ray; ECG, electrocardiography;
HF, heart failure; HFpEF, heart failure with preserved ejection fraction; LVEDP, left ventricular end diastolic pressure; LVEF, left ventricular ejection
fraction; NT-proBNP, N-terminal proB-type natriuretic peptide; PCWP, pulmonary capillary wedge pressure; TR, tricuspid regurgitation.
Obesity is recognized as an important phenotype of HFpEF higher risk of HF across all categories of body mass in-
and up to 80% of individuals with HFpEF are either over- dex (BMI) and may explain about 50% of HF risk associ-
weight or have obesity.100,133 Physical inactivity and obe- ated with BMI.134 Implementation of lifestyle modifica-
sity are also linked with poor prognosis of HFpEF. Low tion to increase physical activity and weight reduction
cardiorespiratory fitness has been associated with a are important strategies to lower the risk of HF.
159 Acta Cardiol Sin 2024;40:148-171

Yi-Heng Li et al.
The treatment approach for HFpEF with obesity in- multiple comorbidities which contribute to pathophy-
volves a combination of lifestyle modification, pharma- siology of HFpEF and hinder exercise capacity.31,139 En-
cotherapy, and bariatric surgery. People who achieved ³ gaging in appropriate physical activity is widely recog-
10% weight loss had a significant 24% risk reduction of nized for its numerous beneficial effects on CV system
nonfatal MI, stroke, hospitalization for HF, or CV death.135 and exercise-based therapy is emerging as a non-phar-
The goal of lifestyle modification, including dietary change macological intervention for HFpEF.140 Exercise training
and regular physical activity, is to achieve weight loss improves peak oxygen uptake and quality of life but causes
while managing the symptoms and underlying causes of no significant changes in LV systolic or diastolic function
HF. Aerobic physical activity with 30-60 minutes of mo- in patients with HFpEF.141 The 2022 AHA/ACC/HFSA heart
derate to vigorous intensity in most days of the week is failure guideline suggested a Class I recommendation for
recommended for obese adults who want to achieve exercise training in patients with HF regardless of the
body weight loss. Lifestyle intervention with liraglutide LVEF.2 A meta-analysis of supervised exercise training in
have been reported to decrease more visceral adipose stable HFpEF patients indicated that regular aerobic ex-
tissue compared with lifestyle intervention only.136 Phar- ercise could significantly increase peak oxygen uptake
macotherapy for weight loss (liraglutide or orlistat) can by 14% and increase total exercise time by 21% in the
be used for persons with BMI ³ 30 kg/m2 or BMI ³ 27 exercise group compared with 1% decrease in the con-
kg/m2 with adiposity-related complications, such as type trol group. 142 Aerobic exercise also improved the six-
2 diabetes, nonalcoholic fatty liver disease or gout.137 In minute walk distance by 9% compared with only 3% in-
the Semaglutide Treatment Effect in People with obesity crease in control subjects.142 Regarding acute decom-
and HFpEF (STEP-HFpEF) randomized trial, administra- pensated HF and hospitalized patients, the Rehabilitation
tion of semaglutide to patients with HFpEF and obesity Therapy in Older Acute Heart Failure Patients (REHAB-
resulted in significant weight loss, enhancement in exer- HF) trial showed that early, transitional, tailored rehabil-
cise capacity, greater decrease in NT-proBNP levels, and itation improved physical function and quality of life but
reduced occurrence of adjudicated HF events compared had no beneficial effect on rehospitalization or death
to the placebo group.138 The ongoing SUMMIT (A Study than usual care.143 Among the individuals in REHAB-HF
of Tirzepatide in Participants With Heart Failure With study, patients with HFpEF might derive greater benefits
Preserved Ejection Fraction and Obesity) trial may pro- from early physical rehabilitation for the outcomes of
vide important insight into the potential benefit and all-cause death, HF rehospitalization, and physical per-
safety of pharmacological weight loss in HFpEF. Bariatric formance than those with HFrEF.144
surgery can be considered for people with BMI ³ 40 However, there are some controversial issues regard-
kg/m2 or BMI ³ 35 kg/m2 with at least 1 adiposity-re- ing the exercise-based therapy in HFpEF. First, the evi-
lated complication to reduce long-term overall mortality. dence is still limited for exercise training to improve clinical
Those with BMI ³ 35 kg/m2 should be considered to re- outcomes and LV diastolic function of HFpEF. In addition,
fer to a multidisciplinary team of medical, surgical, and the setting and modalities of exercise training varied signif-
nutritional experts for obesity treatment.100 icantly among clinical trials and there is no standard proto-
col for the exercise-based therapy for HF. Despite the un-
Recommendation certainties, this guideline still recommends exercise train-
· Weight reduction is recommended for obese patients ing as a non-pharmacological therapy for HFpEF because it
with HFpEF. (COR I, LOE B) is safe and offers substantial improvement in exercise ca-
· Pharmacotherapy for weight reduction should be con- pacity and quality of life for patients with HFpEF. It is cru-
sidered for obese patients with HFpEF to improve HF cial to note that these exercise prescriptions should be su-
symptoms, exercise capacity, and quality of life. (COR pervised, individualized, and carefully monitored. A multi-
I, LOE B) disciplinary approach involving collaboration among car-
diologists, exercise physiologists, and physical therapists
Exercise training should be considered to optimize the implementation of
A significant number of patients with HFpEF have exercise training and ensure patient safety.
Acta Cardiol Sin 2024;40:148-171 160

Recommendation received a pneumococcal vaccine, the administration of

· Supervised exercise training is recommended for pa- PCV13 followed by PPV23 1 year later is recommended
tients with HFpEF. (COR I, LOE B) for HF patients.
Vaccination Recommendation
Pneumonia and respiratory tract infection are im- · Influenza and pneumococcal vaccinations are recom-
portant triggers of HF decompensation and cause hospi- mended for patients with HFpEF, especially for the el-
talization. The risk of pneumonia is high in HF patients derly. (COR I, LOE B)
especially for HFpEF.145 The infection events not only in-
crease the in-hospital mortality of HF, but also results in Management of comorbidities
poor long-term prognosis.146 Influenza and pneumococ- HFpEF is usually associated with multiple comorbi-
cal vaccines help to prevent respiratory infections that dities, such as hypertension, DM, CKD, CAD, or AF. Deliv-
may probably reduce the risk of exacerbation of HF. ering therapy for underlying comorbidities and treating
Numerous studies have provided evidence that the modifiable HF risk factors are mandatory for HFpEF treat-
influenza vaccine has the potential to decrease CV mor- ment.
bidity and mortality in patients undergoing secondary
prevention for CAD, particularly among the elderly po- Hypertension and diabetes
pulation.147 In Taiwan, elderly MI patients who received Hypertension is the leading cause of HFpEF with a
influenza vaccination had a lower risk of all-cause mor- prevalence ranging from 60% to 89% in HFpEF.17 In line
tality and hospitalization for HF.148 So far, there has been with the Hypertension Guideline of Taiwan Society of
no large-scale randomized clinical trial to evaluate the Cardiology, the systolic blood pressure target for HFpEF
efficacy of influenza vaccination in HF patients. Retro- should be less than 130 mmHg.152 The patient’s other
spective analysis of the Prospective Comparison of ARNI comorbidities, such as diabetes, CKD, or CAD, should
with angiotensin converting enzyme inhibitor (ACEI) to guide the personalized choice of antihypertensive agents.
Determine Impact on Global Mortality and Morbidity in The preferred agents for hypertension control in HFpEF
Heart Failure (PARADIGM-HF) trial demonstrated that include diuretics, angiotensin receptor blocker (ARB),
HF patients received influenza vaccination had a signifi- and mineralocorticoid receptor antagonist (MRA) be-
cant lower risk of all-cause mortality, but the CV death cause these agents also have some beneficial effects for
and HF hospitalization did not reach statistical signifi- HFpEF in addition to blood pressure reduction. Since ch-
cance.149 The current European guidelines recommend ronotropic incompetence is a potential mechanism con-
annual influenza vaccinations for HF patients, especially tributing to exercise functional limitation in HFpEF, use
the elderly.9 of beta-blockers in HFpEF may be avoided if there are no
Previous observational study found that patients di- other specific indications for beta-blockers.153 Given the
agnosed with pneumococcal pneumonia faced a signifi- recently demonstrated benefits of sodium-glucose co-
cant risk of acute CV events, including MI, arrhythmia, transporter 2 (SGLT2) inhibitors in improving outcomes
and development or worsening of HF.150 Currently, there in patients with HFpEF,154-156 SGLT2 inhibitors should be
are two types of vaccines for prevention of S. pneumoniae prescribed as first-line therapy for diabetic patients with
infection: the 23-valent pneumococcal polysaccharide HFpEF. However, the use of SGLT2 inhibitors is not recom-
vaccine (PPV23) and the 13-valent pneumococcal conju- mended if estimated glomerular filtration rate (eGFR) is
gate vaccine (PCV13). The effectiveness of vaccines in < 20 mL/min/1.73 m2. SGLT2 inhibitors should also be
preventing invasive pneumococcal infections varies, avoided in all patients with type 1 diabetes, or in type 2
ranging from approximately 56% to 75%.7,151 The effi- diabetes with prior diabetic ketoacidosis (DKA) or a con-
cacy for pneumococcal vaccination specifically for HF dition predisposing to DKA, including pancreatic insuffi-
patients is not well established due to lack of large-scale ciency, drug or alcohol addiction, and prolonged fasting.
randomized controlled trials. Based on expert consen- Metformin is also recommended as first-line therapy for
sus, in adults ³ 65 years of age who have not previously glycemic control in diabetic patients with HFpEF. Given
161 Acta Cardiol Sin 2024;40:148-171

Yi-Heng Li et al.
the substantial weight loss effect of the glucagon-like strategy than antiarrhythmic medications for rhythm con-
peptide-1 receptor agonists (GLP1RA), these agents should trol.160 This guideline recommends that patients with
be considered for HFpEF patients with DM and obesity. HFpEF and AF should have adequate rate control. Beta-
Due to an increased risk of fluid retention, weight gain, blockers and non-dihydropyridine calcium-channel bloc-
and HF events, thiazolidinediones are relatively contra- kers are the usual first-line agents. A recent clinical trial
indicated in diabetic patients with HFpEF. demonstrated that digoxin may improve functional ca-
pacity and reduce more NT-proBNP over bisoprolol in AF
Recommendation patients with HF symptoms.161
· Diuretics, ARB, and MRA are recommended for hyper-
tension in patients with HFpEF. (COR IIa, LOE C) Recommendation
· SGLT2 inhibitors are recommended for diabetes in pa- · SGLT2 inhibitors, ARNI or ARB are recommended for
tients with HFpEF. (COR I, LOE A) CKD in patients with HFpEF. (COR I, LOE A)
· GLP1RA should be considered for diabetes and obe- · Beta-blockers, non-dihydropyridine calcium-channel
sity in patients with HFpEF. (COR I, LOE B) blockers or digoxin are recommended for rate control
in patients with HFpEF and AF (COR IIa, LOE B)
CKD, CAD and AF
Patients with HFpEF and CKD should be treated with Pharmacological treatment
evidence-based therapies that reduce the progression
of CKD. SGLT2 inhibitors have been shown to improve Diuretics
renal outcome in patients with CKD. Although there is HFpEF patients with volume overload should be treated
an expected initial decline in eGFR of approximately 4 with diuretics.48 Loop diuretics should be initiated as the
mL/min/1.73 m2 when initiation of SGLT2 inhibitors, the first-line therapy with the type and dose depending on
rate of eGFR decline is slower compared to patients not the severity of congestion. For those patients with loop
on SGLT2 inhibitors after long term follow up.154-156 Clini- diuretic resistance, sequential nephron blockade can be
cal trials also demonstrated significant slow-down of achieved using thiazide diuretics and/or MRA.
eGFR decline in patients treated with ARB or angioten-
sin receptor-neprilysin inhibitor (ARNI).157 CAD is preva- Recommendation
lent in HFpEF.158 To determine the severity of CAD and · Diuretics are recommended for HFpEF patients with
assess the need for revascularization, CT coronary an- congestion to relief symptoms. (COR I, LOE C)
giography should be considered in patients with a low to
intermediate pretest probability of CAD or those with SGLT2 inhibitor
equivocal non-invasive stress tests. Invasive coronary Both empagliflozin and dapagliflozin have shown their
angiography may be considered in patients with an in- clear benefits in the management of HFpEF. The Empa-
termediate to high pretest probability of CAD. Medical gliflozin Outcome Trial in Patients with Chronic Heart Fai-
therapies of CAD should be given according to the recom- lure with Preserved Ejection Fraction (EMPEROR-Preser-
mendations from the Guidelines of the Taiwan Society ved) trial first demonstrated the advantages of empagli-
of Cardiology on the diagnosis and management of ch- flozin over placebo on the reduction of HF hospitaliza-
ronic coronary syndrome.7 Currently, there are no pro- tion or CV death among 5988 patients with HF and LVEF
spective randomized trials to evaluate the effect of > 40% (hazard ratio: 0.79, 95% confidence interval: 0.69-
revascularization on patients with HFpEF and CAD. For 0.90).154 In addition, empagliflozin also reduced total HF
AF, anticoagulant remains the cornerstone therapy for hospitalization by 27% and delayed the decline of eGFR.154
AF and HFpEF to prevent stroke and the indication for The pre-specified analysis clearly showed empagliflozin
anticoagulation is determined by CHA2DS2-VASc score. reduced the risk of HF hospitalization or CV death by 17%
Randomized control trials did not demonstrate an ad- in patients with LVEF ³ 50%. The Dapagliflozin Evaluation
vantage of rhythm control with antiarrhythmic medica- to Improve the Lives of Patients with Preserved Ejection
tions over rate control.159 Ablation of AF may be a better Fraction Heart Failure (DELIVER) trial investigated the ef-
Acta Cardiol Sin 2024;40:148-171 162

fect of dapagliflozin in 6263 patients with HF and LVEF > sterone Antagonist (TOPCAT) trial did not demonstrate
40% and showed similar results.156 Patients can be en- mortality benefit or reduction in HF hospitalization in
rolled as outpatients or during hospitalization after sta- the whole study with LVEF 45% or greater, the benefits
bilization for HF. The trial demonstrated a significant 18% of spironolactone was shown at the lower end (up to
reduction in the risk of the primary composite endpoint 55%) of HFpEF.167 Its subgroup geographic analyses also
(CV death or worsening heart failure) with dapagliflozin, demonstrated that there was a significant improved
primarily due to the reduced HF events, but not CV mor- prognosis for the 1767 enrolled patients from north and
tality. The benefit of dapagliflozin were found to be con- south America.168 Several upcoming studies (FINEARTS-
sistent in the subgroup analyzes comparing patients with HF, SPIRRIT, and SPIRIT-HF) are still undergoing to clarify
LVEF ³ 60% and LVEF < 60% suggesting no attenuation the definite role of MRAs, including finerenone or spiro-
of benefit in patients with higher LVEF.156 The therapeu- nolactone, in HFpEF. An individual patient-level meta-
tic benefit with dapagliflozin was observed consistently, analysis demonstrated the benefits of candesartan, spi-
independent of age, BMI, frailty class, presence of AF, or ronolactone, and ARNI extending to the lower end of
New York Heart Association functional class. The time to the LVEF range of HFpEF.169 Therefore, in selected pa-
first statistically significant reduction of the primary tients with HFpEF, MRA and ARNI may be considered to
endpoint was only 13 days in DELIVER trial and 18 days decrease HF hospitalizations. An ARB may be considered
in EMPEROR-Preserved study.154-156 SGLT2 inhibitor, em- for patients with HFpEF who are eligible for ARNI but
pagliflozin or dapagliflozin, is recommended as a foun- cannot take it due to cost or intolerance. Combination
dation therapy for HFpEF and should be initiated as early therapy of ARNI, MRA and SGLT2 inhibitor is reasonable
as possible. and was estimated to reduce CV death and HF hospital-
ization among HF patients with LVEF between 45% to
Recommendation 65%.170 An expert consensus from the Taiwan Society of
· SGLT2 inhibitor, empagliflozin or dapagliflozin, is re- Cardiology suggests a sequencing strategy starting with
commended for patients with HFpEF to reduce the SGLT2 inhibitor first and combining it with ARNI if sys-
risk of worsening HF event or CV death. (COR I, LOE A) tolic blood pressure is ³ 100 mmHg or MRA if systolic
BP is < 100 mmHg for HFpEF treatment.10
Renin-angiotensin system inhibitor and MRA
Randomized clinical trials of ACEI and ARB, including Recommendation
perindopril in the Perindopril in Elderly People with · ARNI and MRA are recommended for selected groups
Chronic Heart Failure (PEP-CHF) trial,162 candesartan in of patients with HFpEF. (COR IIa, LOE B)
the Candesartan in Heart Failure: Assessment of Reduc- · ARB is recommended as an alternative for HFpEF who
tion in Mortality and Morbidity-Preserved (CHARM-Pre- cannot tolerate or afford ARNI. (COR IIa, LOE B)
served) trial163 and irbesartan in the Irbesartan in Heart · Combination therapy of SGLT2 inhibitor, ARNI and/or
Failure with Preserved Ejection Fraction Study (I-Pre- MRA is reasonable in selected group of patients with
serve) trial,164 failed to achieve a significant reduction HFpEF. (COR IIb, LOE C)
in the primary outcome compared with placebo for pa-
tients with HFpEF. In the Prospective Comparison of Beta-blocker
ARNI with ARB Global Outcomes in HF with Preserved In the Rate Control Therapy Evaluation in Perma-
Ejection Fraction (PARAGON-HF) trial, ARNI did not sig- nent Atrial Fibrillation (RATE-AF) study that compare
nificantly reduce the risk of HF hospitalization or CV digoxin with bisoprolol in AF patients with HF symp-
death compared with valsartan (p = 0.059), but the toms, the primary outcome of quality of life was com-
benefit of ARNI over ARB was greater in selected groups parable between patients treated with bisoprolol and
of HFpEF patients, such as recently hospitalized patients, digoxin at 6 months.161 But beta-blocker caused more
women and those with an LVEF at or below the median adverse effects, such as dizziness, drowsiness, and hypo-
value of 57%.165,166 For MRA, although the Treatment of tension than digoxin.161 Additionally, the improved func-
Preserved Cardiac Function Heart Failure With an Aldo- tional capacity and lower NT-proBNP levels favored di-
163 Acta Cardiol Sin 2024;40:148-171

Yi-Heng Li et al.
goxin group at 12 months. An individual patient-level fore discharge following HF hospitalization. The Safety,
meta-analysis failed to demonstrate the benefit of beta- Tolerability and Efficacy of Up-titration of Guideline-di-
blockers over placebo among HFpEF patients.171 A beta- rected Medical Therapies for Acute Heart Failure (STRONG-
blocker is not recommended in patients with HFpEF with- HF) trial, enrolled patients with HFrEF or HFpEF and intro-
out compelling indications, such as CAD, prior MI or rate duced an intensive care strategy involving early initiation
control for AF, especially for those with chronotropic and up-titration of foundation medications for HF. The
incompetence. Figure 2 summarizes the current major strategy has been shown to significantly reduce the rates
non-pharmacological and pharmacological therapies for of all-cause death and HF readmission within 180 days af-
HFpEF. ter acute decompensated HF hospitalization.172 In the trial,
15% patients were HFpEF and the clinical benefit of early
Recommendation initiation and up-titration strategy was observed regardless
· Beta-blocker is not recommended in patients with of the baseline LVEF is £ 40% vs. > 40%.173 It is important
HFpEF without compelling indications (COR III, LOE C) to note that STRONG-HF focused on triple therapy with
renin-angiotensin system inhibitor, beta-blocker and MRA.
Early initiation strategy For patients diagnosed with HFpEF in outpatient clinic or
Early initiation strategy means starting recommended admitted due to acute HFpEF, an early initiation strategy
HF pharmacological therapies as soon as possible, prefera- should include the initiation of SGLT2 inhibitor, empagli-
bly at the clinic visit as the HF is definitely diagnosed or be- flozin or dapagliflozin, and/or diuretics to mitigate the
Figure 2. Current major non-pharmacological and pharmacological therapies for HFpEF. HFpEF, heart failure with preserved ejection fraction;
SGLT2i, sodium-glucose cotransporter 2 inhibitor.
Acta Cardiol Sin 2024;40:148-171 164

risk of HF readmission or mortality. REFERENCES
Recommendation 1. Wang CC, Wu CK, Tsai ML, et al. 2019 focused update of the
· An early initiation and titration strategy of HF founda- guidelines of the Taiwan Society of Cardiology for the diagnosis
tion therapy before discharge and in the first few and treatment of heart failure. Acta Cardiol Sin 2019;35:244-
weeks following a HF hospitalization is recommended 83.
2. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/
to reduce the risk of HF rehospitalization or death.
HFSA guideline for the management of heart failure: a report of
(COR IIa, LOE B)
the American College of Cardiology/American Heart Associa-
tion Joint Committee on Clinical Practice Guidelines. Circula-
tion 2022;145:e895-1032.
FUTURE PERSPECTIVE 3. Steinberg BA, Zhao X, Heidenreich PA, et al. Trends in patients
hospitalized with heart failure and preserved left ventricular
HFpEF is an escalating public health concern ac- ejection fraction: prevalence, therapies, and outcomes. Circu-
lation 2012;126:65-75.
counting for more than half of all HF cases and marked
4. Rajadurai J, Tse HF, Wang CH, et al. Understanding the epidemi-
by elevated morbidity and mortality.174 HFpEF often goes
ology of heart failure to improve management practices: an
unnoticed and leads to extensive utilization of health re- Asia-Pacific perspective. J Card Fail 2017;23:327-39.
source. Treating HFpEF poses formidable challenges in- 5. Bozkurt B, Coats AJS, Tsutsui H, et al. Universal definition and
volving management of comorbidities, non-pharmaco- classification of heart failure: a report of the Heart Failure Soci-
logical treatment, and guideline-based medical thera- ety of America, Heart Failure Association of the European Soci-
pies. In addition to current understanding, gaining more ety of Cardiology, Japanese Heart Failure Society and Writing
Committee of the Universal Definition of Heart Failure: En-
insight into the pathophysiology, including inflamma-
dorsed by the Canadian Heart Failure Society, Heart Failure As-
tion, vascular dysfunction, fibrosis, and tissue remodel-
sociation of India, Cardiac Society of Australia and New Zea-
ing, is essential for developing novel diagnostic method land, and Chinese Heart Failure Association. Eur J Heart Fail
and treatment of HFpEF.175 Research is now concentrat- 2021;23:352-80.
ing on comprehensive phenotyping of HFpEF patients 6. Wang CC, Chen JH, Yu WC, et al. 2012 guidelines of the Taiwan
and evaluating targeted treatment in various subtype of Society of Cardiology (TSOC) for the diagnosis and treatment of
HFpEF.176 Employing machine learning with the help of heart failure. Acta Cardiol Sin 2012;28:161-95.
7. Ueng KC, Chiang CE, Chao TH, et al. 2023 guidelines of the Tai-
artificial intelligence system will become a more rapid
wan Society of Cardiology on the diagnosis and management
method to facilitate HFpEF diagnosis and aids in identi-
of chronic coronary syndrome. Acta Cardiol Sin 2023;39:4-96.
fying subtypes with more precise intervention.177,178 Cli- 8. Francis GS, Cohn JN. Heart failure: mechanisms of cardiac and
nical trials with precision medicine approach in various vascular dysfunction and the rationale for pharmacologic inter-
phenotypes of HFpEF have been conducted.179 Multidis- vention. FASEB J 1990;4:3068-75.
ciplinary collaboration is pivotal for administering qual- 9. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC guidelines
ity care for HFpEF. Capitalizing on evolving therapies and for the diagnosis and treatment of acute and chronic heart fail-
ure. Eur Heart J 2021;42:3599-726.
resolving diagnostic complexities will be a pivotal prospect
10. Chiang CE, Hung CL, Wu YW, et al. 2023 consensus of Taiwan
to redefine HFpEF care. The recommendations in this
Society of Cardiology on the pharmacological treatment of
guideline are proposed based on recent study results. chronic heart failure. Acta Cardiol Sin 2023;39:361-90.
Since the landscape is rapidly evolving, establishing new 11. Reyes EB, Ha JW, Firdaus I, et al. Heart failure across Asia: same
pathways for diagnosis and management of HFpEF driven healthcare burden but differences in organization of care. Int J
by emerging clinical trial data is important in the near fu- Cardiol 2016;223:163-7.
ture. 12. Hung CL, Chao TF, Tsai CT, et al. Prevalence, incidence, lifetime
risks, and outcomes of heart failure in Asia: a nationwide re-
port. JACC Heart Fail 2023;11:1454-6.
13. Wang TD, Huang ST, Wang CY, et al. Nationwide trends in inci-
DECLARATION OF CONFLICT OF INTEREST dence, healthcare utilization, and mortality in hospitalized heart
failure patients in Taiwan. ESC Heart Fail 2020;7:3653-66.
All the authors declare no conflict of interest. 14. Shah KS, Xu H, Matsouaka RA, et al. Heart failure with pre-
165 Acta Cardiol Sin 2024;40:148-171

Yi-Heng Li et al.
served, borderline, and reduced ejection fraction: 5-year out- clinical features of heart failure with preserved ejection frac-
comes. J Am Coll Cardiol 2017;70:2476-86. tion. Card Fail Rev 2022;8:e27.
15. Gerber Y, Weston SA, Redfield MM, et al. A contemporary ap- 31. Shah SJ, Kitzman DW, Borlaug BA, et al. Phenotype-specific
praisal of the heart failure epidemic in Olmsted County, Minne- treatment of heart failure with preserved ejection fraction: a
sota, 2000 to 2010. JAMA Intern Med 2015;175:996-1004. multiorgan roadmap. Circulation 2016;134:73-90.
16. Dunlay SM, Roger VL, Redfield MM. Epidemiology of heart fail- 32. Lin CY, Sung HY, Chen YJ, et al. Personalized management for
ure with preserved ejection fraction. Nat Rev Cardiol 2017;14: heart failure with preserved ejection fraction. J Pers Med 2023;
591-602. 13:746.
17. Owan TE, Hodge DO, Herges RM, et al. Trends in prevalence and 33. Galli E, Bourg C, Kosmala W, et al. Phenomapping heart failure
outcome of heart failure with preserved ejection fraction. N with preserved ejection fraction using machine learning cluster
Engl J Med 2006;355:251-9. analysis: prognostic and therapeutic implications. Heart Fail
18. Tsao CW, Lyass A, Enserro D, et al. Temporal trends in the inci- Clin 2021;17:499-518.
dence of and mortality associated with heart failure with pre- 34. Tromp J, Teng TH, Tay WT, et al. Heart failure with preserved
served and reduced ejection fraction. JACC Heart Fail 2018;6: ejection fraction in Asia. Eur J Heart Fail 2019;21:23-36.
678-85. 35. Tromp J, Tay WT, Ouwerkerk W, et al. Multimorbidity in patients
19. Ho JE, Enserro D, Brouwers FP, et al. Predicting heart failure with heart failure from 11 Asian regions: a prospective cohort
with preserved and reduced ejection fraction: The Interna- study using the ASIAN-HF Registry. PLoS Med 2018;15:e1002541.
tional Collaboration on Heart Failure Subtypes. Circ Heart Fail 36. Wu CK, Lee JK, Chiang FT, et al. Prognostic factors of heart fail-
2016;9:e003116. ure with preserved ejection fraction: a 12-year prospective co-
20. Pandey A, LaMonte M, Klein L, et al. Relationship between hort follow-up study. Int J Cardiol 2014;171:331-7.
physical activity, body mass index, and risk of heart failure. J Am 37. Chien SC, Lo CI, Lin CF, et al. Malnutrition in acute heart failure
Coll Cardiol 2017;69:1129-42. with preserved ejection fraction: clinical correlates and prog-
21. Teo LY, Chan LL, Lam CS. Heart failure with preserved ejection nostic implications. ESC Heart Fail 2019;6:953-64.
fraction in hypertension.Curr Opin Cardiol 2016;31:410-6. 38. Chang PP, Wruck LM, Shahar E, et al. Trends in hospitalizations
22. McHugh K, DeVore AD, Wu J, et al. Heart failure with preserved and survival of acute decompensated heart failure in four US
ejection fraction and diabetes: JACC state-of-the-art review. J communities (2005-2014): ARIC Study Community Surveillance.
Am Coll Cardiol 2019;73:602-11. Circulation 2018;138:12-24.
23. Ter Maaten JM, Damman K, Verhaar MC, et al. Connecting 39. Clark KAA, Reinhardt SW, Chouairi F, et al. Trends in heart fail-
heart failure with preserved ejection fraction and renal dys- ure hospitalizations in the US from 2008 to 2018. J Card Fail
function: the role of endothelial dysfunction and inflamma- 2022;28:171-80.
tion. Eur J Heart Fail 2016;18:588-98. 40. Desai AS, Claggett B, Pfeffer MA, et al. Influence of hospitaliza-
24. John JE, Claggett B, Skali H, et al. Coronary artery disease and tion for cardiovascular versus noncardiovascular reasons on
heart failure with preserved ejection fraction: The ARIC Study. J subsequent mortality in patients with chronic heart failure
Am Heart Assoc 2022;11:e021660. across the spectrum of ejection fraction. Circ Heart Fail 2014;
25. Kotecha D, Lam CS, Van Veldhuisen DJ, et al. Heart failure with 7:895-902.
preserved ejection fraction and atrial fibrillation: vicious twins. 41. Crespo-Leiro MG, Anker SD, Maggioni AP, et al. European Soci-
J Am Coll Cardiol 2016;68:2217-28. ety of Cardiology Heart Failure Long-Term Registry (ESC-HF-LT):
26. Harrington J, Felker GM, Lingvay I, et al. Managing obesity in 1-year follow-up outcomes and differences across regions. Eur J
heart failure: a chance to tip the scales? JACC Heart Fail 2024; Heart Fail 2016;18:613-25.
12:28-34. 42. Chioncel O, Lainscak M, Seferovic PM, et al. Epidemiology and
27. Piccirillo F, Crispino SP, Buzzelli L, et al. A state-of-the-art review one-year outcomes in patients with chronic heart failure and
on sleep apnea syndrome and heart failure. Am J Cardiol 2023; preserved, mid-range and reduced ejection fraction: an analy-
195:57-69. sis of the ESC Heart Failure Long-Term Registry. Eur J Heart Fail
28. Lee PL, Wu YW, Cheng HM, et al. Recommended assessment 2017;19:1574-85.
and management of sleep disordered breathing in patients with 43. Azad N, Lemay G. Management of chronic heart failure in the
atrial fibrillation, hypertension and heart failure: Taiwan Soci- older population. J Geriatr Cardiol 2014;11:329-37.
ety of Cardiology/Taiwan Society of Sleep Medicine/Taiwan So- 44. Hung CL, Chao TF, Su CH, et al. Income level and outcomes in
ciety of Pulmonary and Critical Care Medicine joint consensus patients with heart failure with universal health coverage.
statement. J Formos Med Assoc 2024;123:159-78. Heart 2021;107:208-16.
29. Kara Wegermann K, Fudim M, Henao R, et al. Serum metabo- 45. MacDonald MR, Tay WT, Teng TK, et al. Regional variation of
lites are associated with HFpEF in biopsy-proven nonalcoholic mortality in heart failure with reduced and preserved ejection
fatty liver disease. J Am Heart Assoc 2023;12:e029873. fraction across Asia: outcomes in the ASIAN-HF Registry. J Am
30. Teramoto K, Teng TK, Chandramouli C, et al. Epidemiology and Heart Assoc 2020;9:e012199.
Acta Cardiol Sin 2024;40:148-171 166

46. Shahim B, Kapelios CJ, Savarese G, Lund LH. Global public he- 63. Westermann D, Kasner M, Steendijk P, et al. Role of left ventri-
alth burden of heart failure: an updated review. Card Fail Rev cular stiffness in heart failure with normal ejection fraction.
2023;9:e11. Circulation 2008;117:2051-60.
47. Georgiopoulos G, Figliozzi S, Pateras K, et al. Comparison of de- 64. Borlaug BA, Kane GC, Melenovsky V, Olson TP. Abnormal right
mographic, clinical, biochemical, and imaging findings in hy- ventricular-pulmonary artery coupling with exercise in heart
pertrophic cardiomyopathy prognosis: a network meta-analy- failure with preserved ejection fraction. Eur Heart J 2016;37:
sis. JACC Heart Fail 2023;11:30-41. 3293-302.
48. McDonagh TA, Metra M, Adamo M, et al. 2023 focused update 65. Borlaug BA, Olson TP, Lam CS, et al. Global cardiovascular re-
of the 2021 ESC guidelines for the diagnosis and treatment of serve dysfunction in heart failure with preserved ejection frac-
acute and chronic heart failure. Eur Heart J 2023;44:3627-39. tion. J Am Coll Cardiol 2010;56:845-54.
49. Bayonas-Ruiz A, Muñoz-Franco FM, Sabater-Molina M, et al. 66. Borlaug BA, Lam CS, Roger VL, et al. Contractility and ventricu-
Current therapies for hypertrophic cardiomyopathy: a system- lar systolic stiffening in hypertensive heart disease insights into
atic review and meta-analysis of the literature. ESC Heart Fail the pathogenesis of heart failure with preserved ejection frac-
2023;10:8-23. tion. J Am Coll Cardiol 2009;54:410-8.
50. Huang YH, Lin YH, Yen RF, et al. 2021 advocacy statements for 67. Tan YT, Wenzelburger F, Lee E, et al. The pathophysiology of
the role of 99mTc-pyrophosphate scintigraphy in the diagnosis heart failure with normal ejection fraction: exercise echocar-
of transthyretin cardiac amyloidosis: a report of the Taiwan So- diography reveals complex abnormalities of both systolic and
ciety of Cardiology and the Society of Nuclear Medicine of the diastolic ventricular function involving torsion, untwist, and
Republic of China. Acta Cardiol Sin 2021;37:221-31. longitudinal motion. J Am Coll Cardiol 2009;54:36-46.
51. Wang CC, Chang WT, Lin YH, et al. 2023 expert consensus of the 68. Shah AM, Claggett B, Sweitzer NK, et al. Prognostic importance
Taiwan Society of Cardiology on the diagnosis and treatment of of impaired systolic function in heart failure with preserved
cardiac amyloidosis. Acta Cardiol Sin 2023;39:511-43. ejection fraction and the impact of spironolactone. Circulation
52. Hung CL, Wu YW, Lin CC, et al. 2021 TSOC expert consensus on 2015;132:402-14.
the clinical features, diagnosis, and clinical management of car- 69. Houstis NE, Eisman AS, Pappagianopoulos PP, et al. Exercise in-
diac manifestations of Fabry disease. Acta Cardiol Sin 2021;37: tolerance in heart failure with preserved ejection fraction: di-
337-54. agnosing and ranking its causes using personalized O2 pathway
53. Zile MR. Heart failure with preserved ejection fraction: is this analysis. Circulation 2018;137:148-61.
diastolic heart failure? J Am Coll Cardiol 2003;41:1519-22. 70. Cikes M, Claggett B, Shah AM, et al. Atrial fibrillation in heart
54. van Heerebeek L, Borbély A, Niessen HW, et al. Myocardial failure with preserved ejection fraction: the TOPCAT trial. JACC
structure and function differ in systolic and diastolic heart fail- Heart Fail 2018;6:689-97.
ure. Circulation 2006;113:1966-73. 71. Kuo JY, Jin X, Sun JY, et al. Insights on distinct left atrial remodel-
55. Borbély A, van der Velden J, Papp Z, et al. Cardiomyocyte stiff- ing between atrial fibrillation and heart failure with preserved
ness in diastolic heart failure. Circulation 2005;111:774-81. ejection fraction. Front Cardiovasc Med 2022;9:857360.
56. Aurigemma GP, Gaasch WH. Clinical practice. diastolic heart 72. Zakeri R, Chamberlain AM, Roger VL, Redfield MM. Temporal
failure. N Engl J Med 2004;351:1097-105. relationship and prognostic significance of atrial fibrillation in
57. Zile MR, Baicu CF, Gaasch WH. Diastolic heart failure--abnor- heart failure patients with preserved ejection fraction: a com-
malities in active relaxation and passive stiffness of the left ven- munity-based study. Circulation 2013;128:1085-93.
tricle. N Engl J Med 2004;350:1953-9. 73. Shah SJ, Lam CSP, Svedlund S, et al. Prevalence and correlates of
58. Zile MR, Baicu CF, Bonnema DD. Diastolic heart failure: defini- coronary microvascular dysfunction in heart failure with pre-
tions and terminology. Prog Cardiovasc Dis 2005;47:307-13. served ejection fraction: PROMIS-HFpEF. Eur Heart J 2018;39:
59. van Heerebeek L, Franssen CP, Hamdani N, et al. Molecular and 3439-50.
cellular basis for diastolic dysfunction. Curr Heart Fail Rep 74. van Empel VP, Mariani J, Borlaug BA, Kaye DM. Impaired myo-
2012;9:293-302. cardial oxygen availability contributes to abnormal exercise he-
60. Czuriga D, Paulus WJ, Czuriga I, et al. Cellular mechanisms for modynamics in heart failure with preserved ejection fraction. J
diastolic dysfunction in the human heart. Curr Pharm Biotech- Am Heart Assoc 2014;3:e001293.
nol 2012;13:2532-8. 75. Obokata M, Reddy YNV, Melenovsky V, et al. Myocardial injury
61. Wu CK, Lee JK, Hsu JC, et al. Myocardial adipose deposition and and cardiac reserve in patients with heart failure and preserved
the development of heart failure with preserved ejection frac- ejection fraction. J Am Coll Cardiol 2018;72:29-40.
tion. Eur J Heart Fail 2020;22:445-54. 76. Mohammed SF, Hussain S, Mirzoyev SA, et al. Coronary micro-
62. Jin X, Hung CL, Tay WT, et al. Epicardial adipose tissue related to vascular rarefaction and myocardial fibrosis in heart failure
left atrial and ventricular function in heart failure with pre- with preserved ejection fraction. Circulation 2015;131:550-9.
served versus reduced and mildly reduced ejection fraction. 77. Phan TT, Shivu GN, Abozguia K, et al. Impaired heart rate re-
Eur J Heart Fail 2022;24:1346-56. covery and chronotropic incompetence in patients with heart
167 Acta Cardiol Sin 2024;40:148-171

Yi-Heng Li et al.
failure with preserved ejection fraction. Circ Heart Fail 2010; based study. J Am Coll Cardiol 2009;53:1119-26.
3:29-34. 93. Huang W, Oliveira RKF, Lei H, et al. Pulmonary vascular resis-
78. Sarma S, Stoller D, Hendrix J, et al. Mechanisms of chronotropic tance during exercise predicts long-term outcomes in heart
incompetence in heart failure with preserved ejection fraction. failure with preserved ejection fraction. J Card Fail 2018;24:
Circ Heart Fail 2020;13:e006331. 169-76.
79. Gorter TM, Obokata M, Reddy YNV, et al. Exercise unmasks dis- 94. Saito Y, Obokata M, Harada T, et al. Disproportionate exercise-
tinct pathophysiologic features in heart failure with preserved induced pulmonary hypertension in relation to cardiac output
ejection fraction and pulmonary vascular disease. Eur Heart J in heart failure with preserved ejection fraction: a non-invasive
2018;39:2825-35. echocardiographic study. Eur J Heart Fail 2023;25:792-802.
80. Gorter TM, Hoendermis ES, van Veldhuisen DJ, et al. Right ven- 95. Haykowsky MJ, Brubaker PH, John JM, et al. Determinants of
tricular dysfunction in heart failure with preserved ejection exercise intolerance in elderly heart failure patients with pre-
fraction: a systematic review and meta-analysis. Eur J Heart Fail served ejection fraction. J Am Coll Cardiol 2011;58:265-74.
2016;18:1472-87. 96. Molina AJ, Bharadwaj MS, Van Horn C, et al. Skeletal muscle mi-
81. Melenovsky V, Hwang SJ, Lin G, et al. Right heart dysfunction in tochondrial content, oxidative capacity, and Mfn2 expression
heart failure with preserved ejection fraction. Eur Heart J 2014; are reduced in older patients with heart failure and preserved
35:3452-62. ejection fraction and are related to exercise intolerance. JACC
82. Mohammed SF, Hussain I, AbouEzzeddine OF, et al. Right ven- Heart Fail 2016;4:636-45.
tricular function in heart failure with preserved ejection frac- 97. Kumar AA, Kelly DP, Chirinos JA. Mitochondrial dysfunction in
tion: a community-based study. Circulation 2014;130:2310-20. heart failure with preserved ejection fraction. Circulation 2019;
83. Burke MA, Katz DH, Beussink L, et al. Prognostic importance of 139:1435-50.
pathophysiologic markers in patients with heart failure and 98. Kirkman DL, Bohmke N, Billingsley HE, Carbone S. Sarcopenic
preserved ejection fraction. Circ Heart Fail 2014;7:288-99. obesity in heart failure with preserved ejection fraction. Front
84. Gorter TM, van Veldhuisen DJ, Bauersachs J, et al. Right heart Endocrinol (Lausanne) 2020;11:558271.
dysfunction and failure in heart failure with preserved ejection 99. Olivotto I, Udelson JE, Pieroni M, Rapezzi C. Genetic causes of
fraction: mechanisms and management. Position statement on heart failure with preserved ejection fraction: emerging phar-
behalf of the Heart Failure Association of the European Society macological treatments. Eur Heart J 2023;44:656-67.
of Cardiology. Eur J Heart Fail 2018;20:16-37. 100. Kittleson MM, Panjrath GS, Amancherla K, et al. 2023 ACC ex-
85. Reddy YNV, Andersen MJ, Obokata M, et al. Arterial stiffening pert consensus decision pathway on management of heart fail-
with exercise in patients with heart failure and preserved ejec- ure with preserved ejection fraction: a report of the American
tion fraction. J Am Coll Cardiol 2017;70:136-48. College of Cardiology Solution Set Oversight Committee. J Am
86. Tartière-Kesri L, Tartière JM, Logeart D, et al. Increased proxi- Coll Cardiol 2023;81:1835-78.
mal arterial stiffness and cardiac response with moderate exer- 101. Upadhya B, Kitzman DW. Heart failure with preserved ejection
cise in patients with heart failure and preserved ejection frac- fraction in older adults. Heart Fail Clin 2017;13:485-502.
tion. J Am Coll Cardiol 2012;59:455-61. 102. Lam CSP, Arnott C, Beale AL, et al. Sex differences in heart fail-
87. Yen CH, Lin JL, Sung KT, et al. Association of free fatty acid bind- ure. Eur Heart J 2019;40:3859-68c.
ing protein with central aortic stiffness, myocardial dysfunction 103. McKee PA, Castelli WP, McNamara PM, Kannel WB. The natural
and preserved ejection fraction heart failure. Sci Rep 2021;11: history of congestive heart failure: the Framingham study. N
16501. Engl J Med 1971;285:1441-6.
88. D'Amario D, Migliaro S, Borovac JA, et al. Microvascular dys- 104. Drazner MH, Rame JE, Stevenson LW, Dries DL. Prognostic im-
function in heart failure with preserved ejection fraction. Front portance of elevated jugular venous pressure and a third heart
Physiol 2019;10:1347. sound in patients with heart failure. N Engl J Med 2001;345:
89. Kawaguchi M, Hay I, Fetics B, Kass DA. Combined ventricular 574-81.
systolic and arterial stiffening in patients with heart failure and 105. Thibodeau JT, Turer AT, Gualano SK, et al. Characterization of a
preserved ejection fraction: implications for systolic and dia- novel symptom of advanced heart failure: bendopnea. JACC
stolic reserve limitations. Circulation 2003;107:714-20. Heart Fail 2014;2:24-31.
90. Zhou KN, Sung KT, Yen CH, et al. Carotid arterial mechanics as 106. Felker GM, Cuculich PS, Gheorghiade M. The Valsalva maneu-
useful biomarker of extracellular matrix turnover and preserved ver: a bedside “biomarker” for heart failure. Am J Med 2006;
ejection fraction heart failure. ESC Heart Fail 2020;7:1615-25. 119:117-22.
91. Humbert M, Kovacs G, Hoeper MM, et al. 2022 ESC/ERS guide- 107. Badgett RG, Mulrow CD, Otto PM, Ramirez G. How well can the
lines for the diagnosis and treatment of pulmonary hyperten- chest radiograph diagnose left ventricular dysfunction? J Gen
sion. Eur Heart J 2022;43:3618-731. Intern Med 1996;11:625-34.
92. Lam CS, Roger VL, Rodeheffer RJ, et al. Pulmonary hypertension 108. Zaphiriou A, Robb S, Murray-Thomas T, et al. The diagnostic ac-
in heart failure with preserved ejection fraction: a community- curacy of plasma BNP and NTproBNP in patients referred from
Acta Cardiol Sin 2024;40:148-171 168

primary care with suspected heart failure: results of the UK global longitudinal strain and ejection fraction. Heart 2014;
natriuretic peptide study. Eur J Heart Fail 2005;7:537-41. 100:1673-80.
109. Booth RA, Hill SA, Don-Wauchope A, et al. Performance of BNP 122. Huang CY, Lee JK, Chen ZW, et al. Inhaled prostacyclin on exer-
and NT-proBNP for diagnosis of heart failure in primary care pa- cise echocardiographic cardiac function in preserved ejection
tients: a systematic review. Heart Fail Rev 2014;19:439-51. fraction heart failure. Med Sci Sports Exerc 2020;52:269-77.
110. Horwich TB, Hamilton MA, Fonarow GC. B-type natriuretic pep- 123. Bellenger NG, Burgess MI, Ray SG, et al. Comparison of left ven-
tide levels in obese patients with advanced heart failure. J Am tricular ejection fraction and volumes in heart failure by echo-
Coll Cardiol 2006;47:85-90. cardiography, radionuclide ventriculography and cardiovascu-
111. Mehra MR, Uber PA, Park MH, et al. Obesity and suppressed B- lar magnetic resonance; are they interchangeable? Eur Heart J
type natriuretic peptide levels in heart failure. J Am Coll Cardiol 2000;21:1387-96.
2004;43:1590-5. 124. Kittleson MM, Maurer MS, Ambardekar AV, et al. Cardiac amy-
112. Anwaruddin S, Lloyd-Jones DM, Baggish A, et al. Renal func- loidosis: evolving diagnosis and management: a scientific sta-
tion, congestive heart failure, and amino-terminal pro-brain tement from the American Heart Association. Circulation 2020;
natriuretic peptide measurement: results from the ProBNP In- 142:e7-22.
vestigation of Dyspnea in the Emergency Department (PRIDE) 125. Kouranos V, Sharma R. Cardiac sarcoidosis: state-of-the-art re-
Study. J Am Coll Cardiol 2006;47:91-7. view. Heart 2021;107:1591-9.
113. Redfield MM, Rodeheffer RJ, Jacobsen SJ, et al. Plasma brain 126. Pieroni M, Moon JC, Arbustini E, et al. Cardiac involvement in
natriuretic peptide concentration: impact of age and gender. J Fabry disease: JACC review topic of the week. J Am Coll Cardiol
Am Coll Cardiol 2002;40:976-82. 2021;77:922-36.
114. Wu CK, Su MM, Wu YF, et al. Combination of plasma biomar- 127. Kaniewska M, Schuetz GM, Willun S, et al. Noninvasive evalua-
kers and clinical data for the detection of myocardial fibrosis or tion of global and regional left ventricular function using com-
aggravation of heart failure symptoms in heart failure with pre- puted tomography and magnetic resonance imaging: a meta-
served ejection fraction patients. J Clin Med 2018;7:427. analysis. Eur Radiol 2017;27:1640-59.
115. Wu CK, Wang YC, Lee JK, et al. Connective tissue growth factor 128. van Royen N, Jaffe CC, Krumholz HM, et al. Comparison and
and cardiac diastolic dysfunction: human data from the Taiwan reproducibility of visual echocardiographic and quantitative
diastolic heart failure registry and molecular basis by cellular radionuclide left ventricular ejection fractions. Am J Cardiol
and animal models. Eur J Heart Fail 2014;16:163-72. 1996;77:843-50.
116. Hung CL, Hung TC, Liu CC, et al. Relation of carbohydrate anti- 129. Saraste A, Knuuti J. PET imaging in heart failure: the role of new
gen-125 to left atrial remodeling and its prognostic usefulness tracers. Heart Fail Rev 2017;22:501-11.
in patients with heart failure and preserved left ventricular 130. Chang SN, Sung KT, Huang WH, et al. Sex, racial differences and
ejection fraction in women. Am J Cardiol 2012;110:993-1000. healthy aging in normative reference ranges on diastolic func-
117. Nauta JF, Hummel YM, van der Meer P, et al. Correlation with tion in ethnic Asians: 2016 ASE guideline revisited. J Formos
invasive left ventricular filling pressures and prognostic rele- Med Assoc 2021;120:2160-75.
vance of the echocardiographic diastolic parameters used in 131. Pieske B, Tschope C, de Boer RA, et al. How to diagnose heart
the 2016 ESC heart failure guidelines and in the 2016 ASE/ failure with preserved ejection fraction: the HFA-PEFF diagnos-
EACVI recommendations: a systematic review in patients with tic algorithm: a consensus recommendation from the Heart
heart failure with preserved ejection fraction. Eur J Heart Fail Failure Association (HFA) of the European Society of Cardiology
2018;20:1303-11. (ESC). Eur Heart J 2019;40:3297-317.
118. Al Saikhan L, Park C, Hardy R, Hughes A. Prognostic implications 132. Lin PL. Obesity and cardiovascular disease. Str Circ J 2021;3:1-3.
of left ventricular strain by speckle-tracking echocardiography 133. Clerico A, Zaninotto M, Passino C, Plebani M. Obese phenotype
in the general population: a meta-analysis. Vasc Health Risk and natriuretic peptides in patients with heart failure with pre-
Manag 2019;15:229-51. served ejection fraction. Clin Chem Lab Med 2018;56:1015-25.
119. Chen ZW, Huang CY, Cheng JF, et al. Stress echocardiography- 134. Pandey A, Cornwell WK 3rd, Willis B, et al. Body mass index and
derived E/e¢ predicts abnormal exercise hemodynamics in heart cardiorespiratory fitness in mid-life and risk of heart failure
failure with preserved ejection fraction. Front Physiol 2019;10: hospitalization in older age: findings from the Cooper Center
1470. Longitudinal Study. JACC Heart Fail 2017;5:367-74.
120. Biering-Sorensen T, Biering-Sorensen SR, Olsen FJ, et al. Global 135. Wilding JPH, Jacob S. Cardiovascular outcome trials in obesity:
longitudinal strain by echocardiography predicts long-term risk a review. Obes Rev 2021;22:e13112.
of cardiovascular morbidity and mortality in a low-risk general 136. Santilli F, Simeone PG, Guagnano MT, et al. Effects of liraglutide
population: The Copenhagen City Heart Study. Circ Cardiovasc on weight loss, fat distribution, and beta-cell function in bbese
Imaging 2017;10:e005521. subjects with prediabetes or early type 2 diabetes. Diabetes
121. Kalam K, Otahal P, Marwick TH. Prognostic implications of glo- Care 2017;40:1556-64.
bal LV dysfunction: a systematic review and meta-analysis of 137. Wharton S, Lau DCW, Vallis M, et al. Obesity in adults: a clinical
169 Acta Cardiol Sin 2024;40:148-171

Yi-Heng Li et al.
practice guideline. CMAJ 2020;192:E875-91. ejection fraction. J Am Coll Cardiol 2021;78:2042-56.

138. Kosiborod MN, Abildstrøm SZ, Borlaug BA, et al. Semaglutide in 154. Anker SD, Butler J, Filippatos G, et al. Empagliflozin in heart fail-
patients with heart failure with preserved ejection fraction and ure with a preserved ejection fraction. N Engl J Med 2021;385:
obesity. N Engl J Med 2023;389:1069-84. 1451-61.
139. Sharma K, Kass DA. Heart failure with preserved ejection frac- 155. Nassif ME, Windsor SL, Borlaug BA, et al. The SGLT2 inhibitor
tion: mechanisms, clinical features, and therapies. Circ Res dapagliflozin in heart failure with preserved ejection fraction: a
2014;115:79-96. multicenter randomized trial. Nat Med 2021;27:1954-60.
140. Nystoriak MA, Bhatnagar A. Cardiovascular effects and benefits 156. Solomon SD, McMurray JJV, Claggett B, et al. Dapagliflozin in
of exercise. Front Cardiovasc Med 2018;5:135. heart failure with mildly reduced or preserved ejection frac-
141. Pandey A, Parashar A, Kumbhani D, et al. Exercise training in tion. N Engl J Med 2022;387:1089-98.
patients with heart failure and preserved ejection fraction: 157. Mc Causland FR, Lefkowitz MP, Claggett B, et al. Angiotensin-
meta-analysis of randomized control trials. Circ Heart Fail 2015; neprilysin inhibition and renal outcomes in heart failure with
8:33-40. preserved ejection fraction. Circulation 2020;142:1236-45.
142. Sachdev V, Sharma K, Keteyian SJ, et al. Supervised exercise 158. Rush CJ, Berry C, Oldroyd KG, et al. Prevalence of coronary ar-
training for chronic heart failure with preserved ejection frac- tery disease and coronary microvascular dysfunction in pati-
tion: a scientific statement from the American Heart Associa- ents with heart failure with preserved ejection fraction. JAMA
tion and American College of Cardiology. Circulation 2023;147: Cardiol 2021;6:1130-43.
e699-715. 159. Roy D, Talajic M, Nattel S, et al. Rhythm control versus rate con-
143. Kitzman DW, Whellan DJ, Duncan P, et al. Physical rehabilitation trol for atrial fibrillation and heart failure. N Engl J Med 2008;
for older patients hospitalized for heart failure. N Engl J Med 358:2667-77.
2021;385:203-16. 160. Packer DL, Piccini JP, Monahan KH, et al. Ablation versus drug
144. Mentz RJ, Whellan DJ, Reeves GR, et al. Rehabilitation interven- therapy for atrial fibrillation in heart failure: results from the
tion in older patients with acute heart failure with preserved CABANA trial. Circulation 2021;143:1377-90.
versus reduced ejection fraction. JACC Heart Fail 2021;9:747- 161. Kotecha D, Bunting KV, Gill SK, et al.; Rate Control Therapy
57. Evaluation in Permanent Atrial Fibrillation (RATE-AF) Team. Ef-
145. Shen L, Jhund PS, Anand IS, et al. Incidence and outcomes of fect of digoxin vs bisoprolol for heart rate control in atrial fibril-
pneumonia in patients with heart failure. J Am Coll Cardiol lation on patient-reported quality of life: the RATE-AF random-
2021;77:1961-73. ized clinical trial. JAMA 2020;324:2497-508.
146. Chen CY, Lee CH, Lin HW, et al. Impact of infection-related ad- 162. Cleland JG, Tendera M, Adamus J, et al. The perindopril in el-
mission in patients with heart failure: a 10 years national co- derly people with chronic heart failure (PEP-CHF) study. Eur
hort study. Sci Rep 2023;13:6941. Heart J 2006;27:2338-45.
147. Fountoulaki K, Tsiodras S, Polyzogopoulou E, et al. Beneficial ef- 163. Yusuf S, Pfeffer MA, Swedberg K, et al. Effects of candesartan in
fects of vaccination on cardiovascular events: myocardial inpatients with chronic heart failure and preserved left-ventricu-
farction, stroke, heart failure. Cardiology 2018;141:98-106. lar ejection fraction: the CHARM-Preserved trial. Lancet 2003;
148. Wu HH, Chang YY, Kuo SC, Chen YT. Influenza vaccination and 362:777-81.
secondary prevention of cardiovascular disease among Tai- 164. Massie BM, Carson PE, McMurray JJ, et al. Irbesartan in pati-
wanese elders-a propensity score-matched follow-up study. ents with heart failure and preserved ejection fraction. N Engl J
PLoS One 2019;14:e0219172. Med 2008;359:2456-67.
149. Vardeny O, Claggett B, Udell JA, et al. Influenza vaccination in 165. Solomon SD, McMurray JJV, Anand IS, et al.; PARAGON-HF In-
patients with chronic heart failure: The PARADIGM-HF Trial. vestigators and Committees. Angiotensin-neprilysin inhibition
JACC Heart Fail 2016;4:152-8. in heart failure with preserved ejection fraction. N Engl J Med
150. Musher DM, Rueda AM, Kaka AS, Mapara SM. The association 2019;381:1609-20.
between pneumococcal pneumonia and acute cardiac events. 166. Vaduganathan M, Claggett BL, Desai AS, et al. Prior heart failure
Clin Infect Dis 2007;45:158-65. hospitalization, clinical outcomes, and response to sacubitril/
151. Pilishvili T, Bennett NM. Pneumococcal disease prevention valsartan compared with valsartan in HFpEF. J Am Coll Cardiol
among adults: strategies for the use of pneumococcal vaccines. 2020;75:245-54.
Vaccine 2015;33(Suppl 4):D60-5. 167. Solomon SD, Claggett B, Lewis EF, et al. Influence of ejection
152. Wang TD, Chiang CE, Chao TH, et al. 2022 guidelines of the Tai- fraction on outcomes and efficacy of spironolactone in patients
wan Society of Cardiology and the Taiwan Hypertension So- with heart failure with preserved ejection fraction. Eur Heart J
ciety for the management of hypertension. Acta Cardiol Sin 2016;37:455-62.
2022;38:225-325. 168. Pfeffer MA, Claggett B, Assmann SF, et al. Regional variation in
153. Palau P, Seller J, Domínguez E, et al. Effect of b-blocker with- patients and outcomes in the Treatment of Preserved Cardiac
drawal on functional capacity in heart failure and preserved Function Heart Failure with an Aldosterone Antagonist (TOPCAT)
Acta Cardiol Sin 2024;40:148-171 170

trial. Circulation 2015;131:34-42. 2131-44.

169. Dewan P, Jackson A, Lam CSP, et al. Interactions between left 174. Redfield MM, Borlaug BA. Heart failure with preserved ejection
ventricular ejection fraction, sex and effect of neurohumoral fraction: a review. JAMA 2023;329:827-38.
modulators in heart failure. Eur J Heart Fail 2020;22:898-901. 175. Simmonds SJ, Cuijpers I, Heymans S, Jones EAV. Cellular and
170. Vaduganathan M, Claggett BL, Inciardi RM, et al. Estimating the molecular differences between HFpEF and HFrEF: a step ahead
benefits of combination medical therapy in heart failure with in an improved pathological understanding. Cells 2020;9:242.
mildly reduced and preserved ejection fraction. Circulation 176. Shah SJ, Borlaug BA, Kitzman DW, et al. Research priorities for
2022;145:1741-3. heart failure with preserved ejection fraction. Circulation 2020;
171. Cleland JGF, Bunting KV, Flather MD, et al. Beta-blockers for 141:1001-26.
heart failure with reduced, mid-range, and preserved ejection 177. Tromp J, Seekings PJ, Hung CL, et al. Automated interpretation
fraction: an individual patient-level analysis of double-blind of systolic and diastolic function on the echocardiogram: a mul-
randomized trials. Eur Heart J 2018;39:26-35. ticohort study. Lancet Digit Health 2022;4:e46-54.
172. Mebazaa A, Davison B, Chioncel O, et al. Safety, tolerability and 178. Chiou YA, Hung CL, Lin SF. AI-assisted echocardiographic pre-
efficacy of up-titration of guideline-directed medical therapies screening of heart failure with preserved ejection fraction on
for acute heart failure (STRONG-HF): a multinational, open-la- the basis of intrabeat dynamics. JACC Cardiovasc Imaging 2021;
bel, randomised, trial. Lancet 2022;400:1938-52. 14:2091-104.
173. Pagnesi M, Metra M, Cohen-Solal A, et al. Uptitrating treat- 179. Heinzel FR, Shah SJ. The future of heart failure with preserved
ment after heart failure hospitalization across the spectrum of ejection fraction: deep phenotyping for targeted therapeutics.
left ventricular ejection fraction. J Am Coll Cardiol 2023;81: Herz 2022;47:308-23.
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Acta Cardiol Sin 2024;40:148-171

Guidelines doi: 10.6515/ACS.202403_40(2).20240206A

2024 Guidelines of the Taiwan Society of

Received: January 8, 2024 Accepted: February 6, 2024

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Table 2. Relative distribution of HFpEF in cross-sectional and longitudinal observational studies

Incidence of HFpEF HFrEF HFpEF

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Table 3. Pathophysiology of HFpEF involved in aging, female, and different comorbidities

Table 4. The Framingham diagnostic criteria of heart failure

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Recommendation received a pneumococcal vaccine, the administration of

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risk of HF readmission or mortality. REFERENCES

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practice guideline. CMAJ 2020;192:E875-91. ejection fraction. J Am Coll Cardiol 2021;78:2042-56.

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trial. Circulation 2015;131:34-42. 2131-44.

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