For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts.
Initially, heart failure was a condition with reduced ejection fraction—HFrEF.1 Later on it was noted that patients with near normal or normal ejection fraction could also present with symptoms of heart failure, a condition labelled as heart failure with preserved ejection fraction or HFpEF,2 which remains an enigma and a challenge for clinicians. The current focus issue on heart failure starts with ‘The year in cardiology: heart failure’ by John Cleland from the Imperial College and Glasgow University in the UK, and colleagues. The authors note that 2019 brought many new concepts and an abundance of new data on the nature, management, and outcome of HFrEF and HFpEF. The importance of these novel findings reviewed in this article is further supported by the fact that the outcome of cardiovascular disease is determined to a large extent by the ability to delay or prevent the development of heart failure.3 Accordingly, attention is shifting to earlier diagnosis of and intervention for heart failure. Patients with type-2 diabetes mellitus4 or coronary artery disease5 have a relatively good prognosis unless plasma concentrations of natriuretic peptides are increased, reflecting cardiac or renal dysfunction. Adoption of a simple ‘Universal Definition’ of heart failure based on natriuretic peptides would facilitate early diagnosis and treatment,6 but will lead to an enormous increase in its prevalence.
The 2016 ESC Guidelines have defined three categories of heart failure based on left ventricular ejection fraction (LVEF7). However, the evidence for this is lacking, in particular for the limits currently defined.1 It continues to remain a matter of debate where the sweet spot of LVEF lies. This has been properly addressed in the FAST TRACK ‘Routinely reported ejection fraction and mortality in clinical practice: where does the nadir of risk lie?’ by Brandon Fornwalt and colleagues from Geisinger in Danville, Pennsylvania, USA.8 Physician-reported LVEF on 403 977 echocardiograms from 203 135 patients were linked to all-cause mortality using electronic health records. A data set of 45 531 echocardiograms and 35 976 patients from New Zealand provided independent validation. Overall, adjusted hazard ratios (HRs) for mortality showed a U-shaped relationship for LVEF, with a nadir of risk at 60–65%, a HR of 1.71 with ≥70% and a HR of 1.73 in the range of 35–40% (Figure 1). Similar relationships with a nadir at 60–65% were observed in the validation data set as well as for each age group and both sexes, and after adjustments for conditions associated with an elevated LVEF, including mitral regurgitation, increased wall thickness, and anaemia. Thus, deviation of LVEF from 60–65% is associated with an increase in mortality regardless of age, sex, or other relevant comorbidities such as heart failure. These data will stimulate debate about the definition of a normal LVEF as well as the possible recognition of phenotypes characterized by supranormal LVEF, as outlined in an Editorial by Jeroen Bax from the Leiden University Medical Center in the Netherlands.9 We may have to rethink whether LVEF is really a useful main criterion to characterize patients with heart failure.
Figure 1
Left ventricular ejection fraction hazard ratios and Kaplan–Meier survival curves in the primary analysis (number of echocardiograms = 403 977). Left ventricular ejection fraction intervals are inclusive of the lower threshold. (A) Error bars represent the 95% confidence interval. (B) Selected left ventricular ejection fraction intervals are shown for clarity. The number at risk includes left ventricular ejection fraction intervals not shown in the figure. LVEF, left ventricular ejection fraction (from Wehner GJ, Jing L, Haggerty CM, Suever JD, Leader JB, Hartzel DN, Kirchner HL, Manus JNA, James N, Ayar Z, Gladding P, Good CW, Cleland JGF, Fornwalt BK. Routinely reported ejection fraction and mortality in clinical practice: where does the nadir of risk lie? See pages 1249–1257).
This becomes even more obvious in specific forms of HFpEF. Cardiac amyloidosis is more common than previously thought10 and typically manifests as HFpEF due to extracellular plaques of aggregated transthyretin or TTR, and is associated with a poor prognosis.11 Despite recent success in halting disease progression with a TTR stabilizer and encouraging preliminary findings with TTR silencers,12 these agents are not targeting pre-existing plaques, but rather just delay or prevent the formation of new plaques, explaining their delayed onset of action in trials.13 In their manuscript entitled ‘A novel monoclonal antibody targeting aggregated transthyretin facilitates its removal and functional recovery in an experimental model’, Jacob George and colleagues from the Kaplan Medical Center in Rehovot, Israel examined a novel IgG1 monoclonal antibody against aggregated TTR in experimental cardiac amyloidosis.14 The antibody immunoprecipitates TTR in the sera of patients with wild-type ATTR and stains cardiac plaques. Furthermore, the antibody facilitates aggregated TTR uptake by myeloid cells and protects cardiomyocytes from TTR-inducible toxicity. In a novel in vivo model of wild-type ATTR amyloidosis, the antibody enhanced the disappearance of pyrophosphate signals, attesting to a rapid amyloid deposit removal and degradation, and also improved echocardiographic measures of cardiac performance. Importantly, a capture enzyme-linked immunosorbent assay (ELISA) developed based on the antibody exhibited higher levels of aggregated TTR in the sera of wild-type ATTR amyloidosis patients as compared with those with heart failure, suggesting a potential applicability in diagnosis and pharmacodynamic guidance of dosing. Thus, the antibody targeting aggregated TTR exhibits beneficial effects in a novel experimental wild-type ATTR and possesses a potential diagnostic utility. Whether this novel antibody could potentially be used as a disease-modifying agent in ATTR amyloidosis is further discussed in a balanced Editorial by Rodney Howard Falk from the Harvard University School of Medicine in Boston, Massachusetts, USA.15
Right ventricular dysfunction is an important determinant of functional status leading to tricuspid regurgitation16,17 and impaired survival in various diseases states.18 However, little is known about its epidemiology and the outcome of patients with severe right ventricular dysfunction. In their article entitled ‘Aetiology and outcomes of severe right ventricular dysfunction’, Ratnasari Padang and colleagues from the Mayo Clinic Minnesota in Rochester, Minnesota, USA examined this issue.19 In 64 728 patients undergoing echocardiography, mild or more severe right ventricular dysfunction occurred in 21%. This study focused on the 1299 or 4% of patients with severe right ventricular dysfunction. The most common causes were left-sided heart diseases in 46%, pulmonary thrombo-embolic disease in 18%, chronic lung disease or hypoxia in 17%, and pulmonary arterial hypertension in 11%. After a mean of 2 years of follow-up (Figure 2), 701 deaths occurred, two-thirds within the first year of diagnosis. The overall probability of survival at 1 and 5 years for the entire cohort was 61% and 35%, respectively. In left heart disease, 1- and 5-year survival rates were 61% and 33%, respectively. In pulmonary arterial hypertension, the corresponding values were 76% and 50%, in thrombo-embolic diseases 71% and 49%, and in chronic lung disease 42% and 8%, respectively. Importantly, moderate to severe tricuspid regurgitation portended worse survival. Thus, 1-year mortality of patients with severe right ventricular dysfunction is high and dependent on the underlying cause, with left heart disease being the most common and prognosis being worst in chronic lung disease. These clinically highly important findings are put into context in an Editorial by Marco Guazzi from the Cardiopulmonary Laboratory of the Cardiology Division at the University of Milano in Italy.20
Figure 2
Aetiology of severe right ventricular dysfunction and their impact on survival. (A) Pie chart summarizing the common aetiologies of severe right ventricular dysfunction in the current era and (B) Kaplan–Meier survival curves of patients with severe right ventricular dysfunction based on the top four most common aetiologies (from Padang R, Chandrashekar N, Indrabhinduwat M, Scott CG, Luis SA, Chandrasekaran K, Michelena HI, Nkomo VT, Pislaru SV, Pellikka PA, Kane GC. Aetiology and outcomes of severe right ventricular dysfunction. See pages 1273–1282).
Traditionally, clinicians measure LVEF and at best left ventricular and pulmonary pressures in the evaluation of heart failure. However, ventricular pressure–volume analysis is the reference method for the study of cardiac mechanics, as pointed out by Nicolas Van Mieghem and colleagues from the Thoraxcenter, Erasmus MC, in Rotterdam, the Netherlands in their review entitled ‘Invasive left ventricle pressure–volume analysis: overview and practical clinical implications’. Indeed, advances in calibration algorithms and measuring techniques brought new perspectives for its application in different research and clinical settings. Simultaneous pressure–volume measurement in the heart chambers offers unique insights into mechanical cardiac efficiency. Beat to beat invasive pressure–volume monitoring can be instrumental in the understanding and management of heart failure, valvular heart disease, and mechanical cardiac support.21
The last article is based on the Geoffrey Rose lecture given at the European Society of Cardiology meeting held in conjunction with the World Congress of Cardiology, in Paris, in 2019 entitled ‘Heart failure can affect everyone: the ESC Geoffrey Rose lecture’ by Karen Sliwa from the University of Cape Town in South Africa.22 In her lecture, she applies the concept of ‘sick individuals versus sick population’ pioneered by Geoffrey Rose 35 years ago to heart failure. Indeed, heart failure not only affects a large spectrum of the population globally,23 but it occurs in all ages and equally in both genders.24 Heart failure, in most parts of the world, is clearly not a disease of the elderly.25 There are multiple and complex pathways leading to heart failure which include various risk factors including communicable diseases and exposure to indoor and environmental pollutants, poverty, and overcrowding, as well as suboptimal access to healthcare systems due to socio-economic inequities.
The issue is further complemented by a Discussion Forum contribution. In a contribution ‘How much can acute heart failure patients with low basic blood pressure (systolic blood pressure 90–100 mmHg) benefit from the use of vasodilators?’ Ying Zhou and colleagues from the First Affiliated Hospital of Nanchang University in Nanchang, China comment on the contribution entitled ‘2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association’ by Piotr Ponikowski from the Clinical Military Hospital in Wroclaw, Poland.7,26
The editors hope that this issue of the European Heart Journal will be of interest to its readers.
With thanks to Amelia Meier-Batschelet for help with compilation of this article.
References
1
Luscher
TF.
Lumpers and splitters: the bumpy road to precision medicine
.
Eur Heart J
2019
;
40
:
3292
–
3296
.
2
Pieske
B
Tschope
C
de Boer
RA
Fraser
AG
Anker
SD
Donal
E
Edelmann
F
Fu
M
Guazzi
M
Lam
CSP
Lancellotti
P
Melenovsky
V
Morris
DA
Nagel
E
Pieske-Kraigher
E
Ponikowski
P
Solomon
SD
Vasan
RS
Rutten
FH
Voors
AA
Ruschitzka
F
Paulus
WJ
Seferovic
P
Filippatos
G.
How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC
).
Eur Heart J
2019
;
40
:
3297
–
3317
.
3
Cleland
JGF
Lyon
AR
McDonagh
T
McMurray
JJV.
The year in cardiology: heart failure
.
Eur Heart J
2020
;
41
:1232–1248.
4
Malmborg
M
Schmiegelow
MDS
Norgaard
CH
Munch
A
Gerds
T
Schou
M
Kistorp
C
Torp-Pedersen
C
Hlatky
MA
Gislason
G.
Does type 2 diabetes confer higher relative rates of cardiovascular events in women compared with men?
Eur Heart J
2019
;doi:10.1093/eurheartj/ehz913.
5
Sundaram
V
Bloom
C
Zakeri
R
Halcox
J
Cohen
A
Bowrin
K
Briere
JB
Banerjee
A
Simon
DI
Cleland
JGF
Rajagopalan
S
Quint
JK.
Temporal trends in the incidence, treatment patterns, and outcomes of coronary artery disease and peripheral artery disease in the UK, 2006–2015
.
Eur Heart J
2019
;doi:10.1093/eurheartj/ehz880.
6
Michou
E
Fahrni
G
Mueller
C.
Quantifying heart failure using natriuretic peptides may help the HEART team in decision-making
.
Eur Heart J
2019
;
40
:
3406
–
3408
.
7
Ponikowski
P
Voors
AA
Anker
SD
Bueno
H
Cleland
JGF
Coats
AJS
Falk
V
Gonzalez-Juanatey
JR
Harjola
VP
Jankowska
EA
Jessup
M
Linde
C
Nihoyannopoulos
P
Parissis
JT
Pieske
B
Riley
JP
Rosano
GMC
Ruilope
LM
Ruschitzka
F
Rutten
FH
van der Meer
P.
2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC
.
Eur Heart J
2016
;
37
:
2129
–
2200
.
8
Wehner
GJ
Jing
L
Haggerty
CM
Suever
JD
Leader
JB
Hartzel
DN
Kirchner
HL
Manus
JNA
James
N
Ayar
Z
Gladding
P
Good
CW
Cleland
JGF
Fornwalt
BK.
Routinely reported ejection fraction and mortality in clinical practice: where does the nadir of risk lie?
Eur Heart J
2020
;
41
:1249–1257.
9
Ng
ACT
Bax
JJ.
Hyperdynamic left ventricular function and the prognostic implications for heart failure with preserved ejection fraction
.
Eur Heart J
2020
;
41
:1258–1259.
10
Ammirati
E
AbouEzzeddine
OF.
Transthyretin amyloidosis in Western Europe: a snapshot from the THAOS registry and a call for further perspectives
.
Eur Heart J
2019
;doi:10.1093/eurheartj/ehz205.
11
Chacko
L
Martone
R
Bandera
F
Lane
T
Martinez-Naharro
A
Boldrini
M
Rezk
T
Whelan
C
Quarta
C
Rowczenio
D
Gilbertson
JA
Wongwarawipat
T
Lachmann
H
Wechalekar
A
Sachchithanantham
S
Mahmood
S
Marcucci
R
Knight
D
Hutt
D
Moon
J
Petrie
A
Cappelli
F
Guazzi
M
Hawkins
PN
Gillmore
JD
Fontana
M.
Echocardiographic phenotype and prognosis in transthyretin cardiac amyloidosis
.
Eur Heart J
2020
;doi:10.1093/eurheartj/ehz905.
12
Emdin
M
Aimo
A
Rapezzi
C
Fontana
M
Perfetto
F
Seferovic
PM
Barison
A
Castiglione
V
Vergaro
G
Giannoni
A
Passino
C
Merlini
G.
Treatment of cardiac transthyretin amyloidosis: an update
.
Eur Heart J
2019
;
40
:
3699
–
3706
.
13
Maurer
MS
Schwartz
JH
Gundapaneni
B
Elliott
PM
Merlini
G
Waddington-Cruz
M
Kristen
AV
Grogan
M
Witteles
R
Damy
T
Drachman
BM
Shah
SJ,
Hanna
M
Judge
DP
Barsdorf
AI
Huber
P
Patterson
TA
Riley
S
Schumacher
J
Stewart
M
Sultan
MB
Rapezzi
C.
Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy
.
N Engl J Med
2018
;
379
:
1007
–
1016
.
14
George
J
Rappaport
M
Shimoni
S
Goland
S
Voldarsky
I
Fabricant
Y
Edri
O
Cuciuc
V
Lifshitz
S
Tshori
S
Fassler
M.
A novel monoclonal antibody targeting aggregated transthyretin facilitates its removal and functional recovery in an experimental model
.
Eur Heart J
2020
;
41
:1260–1270.
15
Falk
RH
Dorbala
S.
An antibody against pre-amyloid oligomers: a potential clinical tool or merely an intriguing observation?
Eur Heart J
2020
;
41
:1271–1272.
16
Lancellotti
P
Fattouch
K
Go
YY.
Secondary tricuspid regurgitation in patients with left ventricular systolic dysfunction: cause for concern or innocent bystander?
Eur Heart J
2018
;
39
:
3593
–
3595
.
17
Topilsky
Y
Inojosa
JM
Benfari
G
Vaturi
O
Maltais
S
Michelena
H
Mankad
S
Enriquez-Sarano
M.
Clinical presentation and outcome of tricuspid regurgitation in patients with systolic dysfunction
.
Eur Heart J
2018
;
39
:
3584
–
3592
.
18
Obokata
M
Reddy
YNV
Melenovsky
V
Pislaru
S
Borlaug
BA.
Deterioration in right ventricular structure and function over time in patients with heart failure and preserved ejection fraction
.
Eur Heart J
2019
;
40
:
689
–
697
.
19
Padang
R
Chandrashekar
N
Indrabhinduwat
M
Scott
CG
Luis
SA
Chandrasekaran
K
Michelena
HI
Nkomo
VT
Pislaru
SV
Pellikka
PA
Kane
GC.
Aetiology and outcomes of severe right ventricular dysfunction
.
Eur Heart J
2020
;
41
:1273–1282.
20
Guazzi
M.
The alarming association between right ventricular dysfunction and outcome: aetiology matters
.
Eur Heart J
2020
;
41
:1283–1285.
21
Bastos
MB
Burkhoff
D
Maly
J
Daemen
J
den Uil
CA
Ameloot
K
Lenzen
M
Mahfoud
F
Zijlstra
F
Schreuder
JJ
Van Mieghem
NM.
Invasive left ventricle pressure-volume analysis: overview and practical clinical implications
.
Eur Heart J
2020
;
41
:1286–1297.
22
Sliwa
K.
Heart failure can affect everyone: the ESC Geoffrey Rose lecture
.
Eur Heart J
2020
;
41
:1298–1306.
23
Lam
CSP
Gamble
GD
Ling
LH
Sim
D
Leong
KTG
Yeo
PSD
Ong
HY
Jaufeerally
F
Ng
TP
Cameron
VA
Poppe
K
Lund
M
Devlin
G
Troughton
R
Richards
AM
Doughty
RN.
Mortality associated with heart failure with preserved vs. reduced ejection fraction in a prospective international multi-ethnic cohort study
.
Eur Heart J
2018
;
39
:
1770
–
1780
.
24
Lam
CSP
Arnott
C
Beale
AL
Chandramouli
C
Hilfiker-Kleiner
D
Kaye
DM
Ky
B
Santema
BT
Sliwa
K
Voors
AA.
Sex differences in heart failure
.
Eur Heart J
2019
;
40
:
3859
–
3868c
.
25
Shanbhag
SM
Greve
AM
Aspelund
T
Schelbert
EB
Cao
JJ
Danielsen
R
Thornorgeirsson
G
Sigurethsson
S
Eiriksdottir
G
Harris
TB
Launer
LJ
Guethnason
V
Arai
AE.
Prevalence and prognosis of ischaemic and non-ischaemic myocardial fibrosis in older adults
.
Eur Heart J
2019
;
40
:
529
–
538
.
26
Zhou
Y
Wen
J
Nie
J.
How much can acute heart failure patients with low basic blood pressure (systolic blood pressure 90–100 mmHg) benefit from the use of vasodilators?
Eur Heart J
2020
;
41
:1307–1308.
Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.
This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
0 σχόλια:
Δημοσίευση σχολίου