1.
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 and Group ESCSD. 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
10
11
Heart J. 2016;37:2129-2200.
2.
van Heerebeek L, Borbely A, Niessen HW, Bronzwaer JG, van der Velden J,
12
Stienen GJ, Linke WA, Laarman GJ, Paulus WJ. Myocardial structure and
13
function differ in systolic and diastolic heart failure. Circulation.
14
2006;113:1966-1973.
15
3.
Olivetti G, Melissari M, Capasso JM, Anversa P. Cardiomyopathy of the aging
16
human heart. Myocyte loss and reactive cellular hypertrophy. Circ Res.
17
1991;68:1560-1568.
18
4.
Babusikova E, Lehotsky J, Dobrota D, Racay P, Kaplan P. Age-associated
23
changes in Ca(2+)-ATPase and oxidative damage in sarcoplasmic reticulum of
rat heart. Physiol Res. 2012;61:453-460.
5.
Gazoti Debessa CR, Mesiano Maifrino LB, Rodrigues de Souza R. Age related
changes of the collagen network of the human heart. Mech Ageing Dev.
2001;122:1049-1058.
6.
Heart J. 2016;37:449-454.
7.
Lakatta EG, Sollott SJ. Perspectives on mammalian cardiovascular aging:
humans to molecules. Comp Biochem Physiol A Mol Integr Physiol.
10
11
Katz AM, Rolett EL. Heart failure: when form fails to follow function. Eur
2002;132:699-721.
8.
Shah SJ, Kitzman DW, Borlaug BA, van Heerebeek L, Zile MR, Kass DA,
12
Paulus WJ. Phenotype-Specific Treatment of Heart Failure With Preserved
13
Ejection Fraction: A Multiorgan Roadmap. Circulation. 2016;134:73-90.
14
9.
Matsumoto K, Onishi A, Yamada H, Kusunose K, Suto M, Hatani Y, Matsuzoe
15
H, Tatsumi K, Tanaka H, Hirata KI. Noninvasive Assessment of Preload
16
Reserve Enhances Risk Stratification of Patients With Heart Failure With
17
Reduced Ejection Fraction. Circ Cardiovasc Imaging. 2018;11:e007160.
18
10.
Yamada H, Kusunose K, Nishio S, Bando M, Hotchi J, Hayashi S, Ise T, Yagi
24
S, Yamaguchi K, Iwase T, Soeki T, Wakatsuki T, Sata M. Pre-load stress
echocardiography for predicting the prognosis in mild heart failure. JACC
Cardiovasc Imaging. 2014;7:641-649.
11.
Kusunose K, Yamada H, Nishio S, Tamai R, Niki T, Yamaguchi K, Taketani Y,
Iwase T, Soeki T, Wakatsuki T, Sata M. Interval from the onset of transmitral
flow to annular velocity is a marker of LV filling pressure. JACC Cardiovasc
Imaging. 2013;6:528-530.
12.
Evidence-Based Approach to Help Guide Diagnosis of Heart Failure With
10
11
Reddy YNV, Carter RE, Obokata M, Redfield MM, Borlaug BA. A Simple,
Preserved Ejection Fraction. Circulation. 2018;138:861-870.
13.
Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L,
12
Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru
13
D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU.
14
Recommendations for cardiac chamber quantification by echocardiography in
15
adults: an update from the American Society of Echocardiography and the
16
European Association of Cardiovascular Imaging. J Am Soc Echocardiogr.
17
2015;28:1-39 e14.
18
14.
Nagueh SF, Smiseth OA, Appleton CP, Byrd BF, 3rd, Dokainish H, Edvardsen
25
T, Flachskampf FA, Gillebert TC, Klein AL, Lancellotti P, Marino P, Oh JK,
Popescu BA, Waggoner AD. Recommendations for the Evaluation of Left
Ventricular Diastolic Function by Echocardiography: An Update from the
American Society of Echocardiography and the European Association of
Cardiovascular Imaging. J Am Soc Echocardiogr. 2016;29:277-314.
15.
dysfunction in cardiac aging. Biochim Biophys Acta. 2015;1847:1424-33.
16.
Olivetti G, Giordano G, Corradi D, Melissari M, Lagrasta C, Gambert SR,
Anversa P. Gender differences and aging: effects on the human heart. J Am Coll
10
11
Tocchi A, Quarles EK, Basisty N, Gitari L, Rabinovitch PS. Mitochondrial
Cardiol. 1995;26:1068-1079.
17.
Cheng S, Fernandes VR, Bluemke DA, McClelland RL, Kronmal RA, Lima
12
JA. Age-related left ventricular remodeling and associated risk for
13
cardiovascular outcomes: the Multi-Ethnic Study of Atherosclerosis. Circ
14
Cardiovasc Imaging. 2009;2:191-198.
15
18.
16
17
18
Lakatta EG. Cardiovascular regulatory mechanisms in advanced age. Physiol
Rev. 1993;73:413-467.
19.
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
26
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.
20.
Kitzman DW, Higginbotham MB, Cobb FR, Sheikh KH, Sullivan MJ. Exercise
intolerance in patients with heart failure and preserved left ventricular systolic
function: failure of the Frank-Starling mechanism. J Am Coll Cardiol.
1991;17:1065-1072.
10
21.
Fujimoto N, Borlaug BA, Lewis GD, Hastings JL, Shafer KM, Bhella PS,
11
Carrick-Ranson G, Levine BD. Hemodynamic responses to rapid saline
12
loading: the impact of age, sex, and heart failure. Circulation. 2013;127:55-62.
13
22.
14
15
Borlaug BA, Kass DA. Ventricular-vascular interaction in heart failure. Heart
Fail Clin. 2008;4:23-36.
23.
Rommel KP, von Roeder M, Oberueck C, Latuscynski K, Besler C, Blazek S,
16
Stiermaier T, Fengler K, Adams V, Sandri M, Linke A, Schuler G, Thiele H,
17
Lurz P. Load-Independent Systolic and Diastolic Right Ventricular Function in
18
Heart Failure With Preserved Ejection Fraction as Assessed by Resting and
27
Handgrip Exercise Pressure-Volume Loops. Circ Heart Fail. 2018;11:e004121.
24.
Reddy YNV, Obokata M, Egbe A, Yang JH, Pislaru S, Lin G, Carter R, Borlaug
BA. Left atrial strain and compliance in the diagnostic evaluation of heart
failure with preserved ejection fraction. Eur J Heart Fail. 2019;21:891-900.
25.
Backhaus SJ, Lange T, George EF, Hellenkamp K, Gertz RJ, Billing M,
Wachter R, Steinmetz M, Kutty S, Raaz U, Lotz J, Friede T, Uecker M,
Hasenfuss G, Seidler T, Schuster A. Exercise Stress Real-Time Cardiac
Magnetic Resonance Imaging for Noninvasive Characterization of Heart
Failure With Preserved Ejection Fraction: The HFpEF-Stress Trial. Circulation.
10
11
2021;143:1484-1498.
26.
Caiani EG, Corsi C, Zamorano J, Sugeng L, MacEneaney P, Weinert L, Battani
12
R, Gutierrez-Chico JL, Koch R, Perez de Isla L, Mor-Avi V, Lang RM.
13
Improved semiautomated quantification of left ventricular volumes and
14
ejection fraction using 3-dimensional echocardiography with a full matrix-
15
array transducer: comparison with magnetic resonance imaging. J Am Soc
16
Echocardiogr. 2005;18:779-788.
17
28
Figure legends
Figure 1. Stroke volume index and E/e’ plot at baseline and during LPP stress for
each age group and patients with HFpEF.
Each plot represents the mean values. The arrows indicate the changes in these
parameters from those obtained under resting conditions to those obtained during leg-
positive pressure (LPP) stress.
LPP = leg-positive pressure, HFpEF = heart failure with preserved ejection fraction, SVi
= stroke volume index.
10
Figure 2. Representative cases of each age-group and a patient with HFpEF.
11
For a healthy young subject (upper left), the stroke volume index (SVi) increased in
12
response to leg-positive pressure (LPP) stress, while the E/e’ ratio remained unchanged.
13
For middle-aged and elderly subjects (upper right and lower left), SVi increased during
14
LPP stress at the expense of the increase in E/e’. For a patient with HFpEF, SVi failed to
15
increase during LPP stress. The E/e’ ratio dramatically increased in response to LPP
16
stress.
17
LPP = leg-positive pressure, LVOT = left ventricular outflow, TMF = transmitral flow,
18
TDI = tissue Doppler imaging, SVi = stroke volume index, HFpEF = heart failure with
29
preserved ejection fraction.
Figure 3. Schematic presentation of the hemodynamic responses on the Guyton
diagram for each subgroup during acute preload-increasing maneuver.
The difference in hemodynamic responses to the increased preload according to age
groupss and HFpEF are schematically presented in the Guyton diagram.
LPP = leg-positive pressure, LV = left ventricular, HFpEF = heart failure with preserved
ejection fraction.
Table 1. Clinical characteristics of patients with HFpEF
Age, y
76 ± 13
Gender, M/F
10/15
BMI
23 ± 4
H2FPEF score
2.6 ± 1.6
Comorbidities, n (%)
Hypertension
14 (56)
Diabetes mellitus
9 (36)
Dyslipidemia
12 (48)
COPD
5 (20)
Cardiac rhythm
Sinus rhythm, n (%)
Atrial fibrillation, n (%)
23 (92)
2 (8)
NYHA functional class, n (%)
II
19 (76)
III
6 (24)
IV
0 (0)
Medications, n (%)
Loop diuretics
14 (56)
Beta-blockers
14 (56)
Spironolactone
6 (24)
ACE-I/ARBs
14 (56)
Hemoglobin, g/dL
12.1 ± 2.1
B-type natriuretic peptide, pg/mL
eGFR, mL/min/1.73m2
158 (105-262)
55.2 ± 20.6
Data are presented as n, mean ± SD, n (%), or median (interquartile range).
HFpEF, heart failure with preserved ejection fraction; COPD, chronic obstructive lung
disease; NYHA, New York Heart Association; ARB, angiotensin II receptor blocker;
ACE-I, angiotensin converting enzyme-inhibitor; eGFR, estimated glomerular filtration
rate.
Table 2. Baseline characteristics for patients with HFpEF and normal controls from 3 age -groups
Variables
Age, y
Gender, M/F
Young
(N=27)
Middle-age
(N=25)
Elderly
(N=25)
HFpEF
(N=25)
ANOVA
P value
23 ± 4
13/14
52 ± 6*
6/19
77 ± 6*†
12/13
76 ± 13*†
10/15
<0.001
0.14
42 ± 12*
16 ± 5
40 ± 6
69 ± 18
1.7 ± 0.5
0.42 ± 0.09*
63 ± 4
1.1 ± 0.3*
27 ± 5
10 ± 2*
8±2
43 ± 7*
24 ± 4
39 ± 9*
14 ± 4*
37 ± 8
81 ± 21
2.2 ± 0.7*†
0.55 ± 0.10*†
63 ± 5
0.8 ± 0.2*†
31 ± 8*†
6 ± 2*†
10 ± 2*†
47 ± 10*
23 ± 5
43 ± 14*
17 ± 8
43 ± 13
110 ± 31*†‡
2.7 ± 0.9*†‡
0.58 ± 0.18*†
61 ± 7
1.3 ± 0.5*‡
51 ± 18*†
6 ± 2*†
15 ± 5*†‡
48 ± 11*
22 ± 5
<0.001
<0.05
0.11
<0.001
<0.001
<0.001
0.07
<0.001
<0.001
<0.001
<0.001
<0.01
0.18
Echocardiographic characteristics
LV volume index, mL/m2
End-diastole
53 ± 10
End-systole
19 ± 4
LVOT-SVi, mL/m
38 ± 7
LV mass index, g/m
69 ± 17
Mass to volume ratio, g/mL
1.3 ± 0.4
Relative wall thickness
0.33 ± 0.06
LVEF, %
64 ± 3
E/A ratio
2.2 ± 0.7
LAVI, mL/m
19 ± 7
e’ velocity, cm/sec
15 ± 2
E/e’ ratio
6±2
RVFAC, %
34 ± 10
TAPSE, mm
22 ± 4
Data are presented as n, mean ± SD, n (%).
HFpEF, heart failure with preserved ejection fraction; SVi, stroke volume index; LV, left ventricular;
LVOT, left ventricular outflow tract; LA, left atrial; LAVI, left atrial volume index; RVFAC, right
ventricular fractional area change; TAPSE, tricuspid annular plane systolic excursion.
* P<0.05 vs. young group, † P<0.05 vs. middle-aged group, ‡ P<0.05 vs elderly group
Table. 3 Changes in hemodynamic and echocardiographic parameters during leg-positive pressure stress for patients with HFpEF and normal controls
from 3 age -groups
Young (N=27)
Hemodynamics
Systolic BP, mmHg
Diastolic BP, mmHg
HR, bpm
SVi, mL/m2
Middle-aged (N=25)
Elderly (N=25)
HFpEF (N=25)
Baseline
LPP
Baseline
LPP
Baseline
LPP
Baseline
LPP
119 ± 16
69 ± 11
69 ± 11
38 ± 7
107 ± 14*
61 ± 11*
67 ± 10
42 ± 8*
115 ± 17
69 ± 10
70 ± 11
40 ± 6
112 ± 16
69 ± 11
66 ± 10*
44 ± 6*
134 ± 22
76 ± 15
74 ± 15
37 ± 8
125 ± 21*
74 ± 10
69 ± 13*
42 ± 8*
129 ± 25
68 ± 13
71 ± 11
43 ± 13
124 ± 23*
70 ± 18
67 ± 12
44 ± 14
55 ± 9
20 ± 4*
64 ± 4
42 ± 12
16 ± 5
63 ± 4
49 ± 15*
16 ± 6
68 ± 5*
39 ± 9
14 ± 4
63 ± 5
43 ± 7*
15 ± 3
66 ± 4*
43 ± 14
17 ± 8
61 ± 7
47 ± 13*
18 ± 9
63 ± 6
86 ± 14*
39 ± 10
2.3 ± 0.7
21 ± 7*
15 ± 2*
6±1
18 ± 4
37 ± 10
23 ± 5*
16 ± 4
72 ± 18
65 ± 13
1.1 ± 0.3
27 ± 5
10 ± 2
8±2
15 ± 4
43 ± 7
24 ± 4
13 ± 4
75 ± 14
69 ± 14
1.1 ± 0.3
30 ± 6*
9±2
9 ± 3*
15 ± 5
54 ± 6*
25 ± 4*
13 ± 3
61 ± 13
83 ± 17
0.8 ± 0.2
31 ± 8
6±2
10 ± 2
20 ± 7
47 ± 10
23 ± 5
13 ± 4
67 ± 13*
83 ± 15
0.8 ± 0.2*
35 ± 11*
6 ± 1*
12 ± 3*
19 ± 6
54 ± 12*
26 ± 4*
14 ± 4*
84 ± 21
72 ± 26
1.3 ± 0.5
51 ± 18
6 ± 12
15 ± 5
23 ± 6
48 ± 11
22 ± 5
14 ± 5
90 ± 23*
73 ± 27
1.4 ± 0.7*
53 ± 18
6±2
17 ± 7*
24 ± 9
48 ± 9
21 ± 6
15 ± 5
Echocardiographic indices
LV volume index, mL/m2
End-diastole
53 ± 10
End-systole
19 ± 4
LVEF, %
64 ± 3
Transmitral flow parameters
E velocity, cm/sec
81 ± 16
A velocity, cm/sec
39 ± 10
E/A ratio
2.2 ± 0.7
LAVI, mL/m
19 ± 7
e’ velocity, cm/sec
15 ± 2
E/e’ ratio
6±2
TR-PG, mmHg
16 ± 5
RVFAC, %
34 ± 10
TAPSE, mm
22 ± 4
IVC diameter, mm
16 ± 4
Data are presented as mean ± SD.
LPP, leg-positive pressure; BP, blood pressure; HR, heart rate; TR, tricuspid regurgitation; PG, pressure gradient; IVC, inferior vena cava. All other
abbreviations as in Table 1 and 2. *P<0.05 vs. baseline.
Table 4. Univariate and multivariate logistic regression analysis to identify HFpEF
Univariate analysis
OR
95% CI
P value
Clinical variables
Age (per 5 years increase)
Gender (female)
H2FpEF score
1.076
0.957
2.968
1.037-1.160
0.381-2.407
1.828-4.817
<0.001
0.93
<0.001
Baseline echocardiographic variables
SVi (per 5 mL/m2 increase)
LVEDVI (per 5 mL/m2 increase)
LV mass index (per 10 g/m2 increase)
RWT (per 0.05 unit increase)
LVEF (per 5% increase)
LAVI (per 5 mL/m2 increase)
E/e’ (per 5 unit increase)
TAPSE (per 5 mm increase)
1.059
0.986
1.063
1.069
0.880
1.251
1.473
0.941
1.007-1.113
0.949-1.024
1.036-1.109
1.032-1.108
0.793-0.976
1.134-1.379
1.240-1.750
0.846-1.045
0.03
0.47
<0.001
<0.001
0.02
<0.001
<0.001
0.26
Variables during LPP stress
Δ SVi (per 5 mL/m2 increase)
Δ E/e’ (per 5 unit increase)
0.754
1.234
0.644-0.883
1.038-1.468
<0.001
0.02
Variables
Multivariate analysis
OR
95% CI
P value
1.051
1.016-1.087
<0.01
1.480
1.181-1.855
<0.001
0.780
0.646-0.941
<0.01
OR, odds ratio; CI, confidence interval. All other abbreviations as in Table 1, 2 and 3.
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