Intracardiac energy inefficiency during decompensated and compensated heart failure

Abstract

Aims

The mechanisms underlying the acute decompensation of heart failure (HF) remain unclear. The present study examined intracardiac dynamics during decompensated HF using echo‐vector flow mapping.

Methods and results

Fifty patients admitted for decompensated HF were prospectively enrolled, and intracardiac energy loss (EL) was assessed by echo‐vector flow mapping at admission (decompensated HF) and discharge (compensated HF). Outcome measures were average EL in the left ventricle (LV) in decompensated and compensated HF and were compared with those in 40 stable non‐HF patients with cardiovascular diseases. The mean age of HF patients was 80.8 ± 12.4 years. The prevalence of both females and atrial fibrillation was 48.0%. The prevalence of HF with a reduced ejection fraction (<40%) (HFrEF) was 34.0%. The prevalence of decompensated HF classified into clinical scenario 1 was 33.3%. Blood pressure and NT‐proBNP were significantly higher in decompensated HF than in compensated HF, while the ejection fraction (EF) was significantly lower. Average EL was significantly higher in compensated HF patients than in non‐HF patients (40 mW/m·L vs. 26 mW/m·L, P = 0.047). A multivariable analysis identified age, systolic blood pressure, LVEF, and the absence of chronic obstructive pulmonary disease as independent risk factors for high LV‐EL regardless of the presence of HF. Furthermore, average EL in HF patients was significantly higher under acute decompensated conditions than under compensated conditions (55 mE/m·L vs. 40 mE/m·L, [+18 mE/m·L, P = 0.03]). Higher EL under decompensated HF conditions was significant in non‐HFrEF (+19 mW/m·L, P = 0.009) and clinical scenario 1 (+23 mW/m·L, P = 0.008). The multivariable analysis identified eGFR as an independent risk factor for a decrease in average LV‐EL under decompensated conditions.

Conclusions

Energy inefficiency in LV was apparent even in stable HF patients and significant under acute decompensated conditions, particularly in HF with preserved EF and clinical scenario 1.

Introduction

Heart failure (HF) is a heterogeneous disease with an inconsistent pathophysiology, which contributes to variations in the treatment and prognosis of individuals. ¹ , ² Additionally, the incomplete understanding of the pathophysiology of acute HF decompensation contributes to high readmission rates. ³ , ⁴ In recent years, invasive pulmonary artery monitoring devices revealed that pulmonary artery pressure gradually increased even before acute HF decompensation, eventually spiking rapidly. ⁵ , ⁶ The pathophysiology of acute decompensation includes the temporary worsening of cardiac function due to fluid retention, decreased urine output, and increased sympathetic nervous system activity. ⁷ , ⁸ , ⁹ However, other factors may also be involved.

Echo vector flow mapping (echo‐VFM) is a novel technology that enables flow velocity vector visualization and energy loss (EL) quantification, calculated as intracardiac energy inefficiency due to viscous dissipation in turbulent blood flow observed by colour Doppler mapping and speckle tracking in echocardiographic images. ¹⁰ , ¹¹ In our previous study, intracardiac energy inefficiency, assessed using echo‐VFM, was associated with the presence of HF (N‐terminal prohormone of brain natriuretic peptide [NT‐proBNP] levels) in patients with atrial fibrillation (AF). ¹² We hypothesized that intracardiac energy inefficiency plays a significant role in the pathophysiology of acute HF decompensation and the aim of this study was to validate this hypothesis.

Methods

Study design

We prospectively enrolled 50 patients admitted for acute decompensated HF, and assessed intracardiac energy loss (EL) by echo‐VFM at admission (decompensated HF) and discharge (compensated HF). Forty non‐HF patients, who were admitted for cardiovascular diseases without HF and recovered, were also prospectively recruited and intracardiac EL was assessed at the time of discharge.

The present study protocol was approved by the Ethics Committee of Mitsubishi Kyoto Hospital and written informed consent for the procedure was obtained from all patients.

Echocardiographic image acquisition and vector flow mapping analysis

Transthoracic echocardiography was performed using commercially available ultrasonic equipment (Vivid S5, GE Healthcare Japan, Tokyo, Japan) at the left lateral decubitus position (Figure  1 ). An apical long‐axis view with colour Doppler imaging focused on the left ventricle (LV) was acquired using a GP3DCRS probe with a frame rate of approximately 20–30 frames/s. Colour Doppler movies of more than 5 continuous cardiac cycles were stored in the DICOM file format and transferred to a VFM workstation (iTEcho, Cardio Flow Design Inc., Tokyo, Japan).

Figure 1.

Vector flow mapping in HF and non‐HF patients. EL, energy loss; HF, heart failure.

VFM enables the detection of EL from blood flow velocity through the viscous fraction. Intracardiac EL is calculated according to the following equation:

$$\text{Energy loss}=\int \mathrm{\mu }\sum _{\mathrm{i},\mathrm{j}}{\left(\frac{\partial {\mathrm{u}}_{\mathrm{j}}}{\partial {\mathrm{x}}_{\mathrm{i}}}+\frac{\partial {\mathrm{u}}_{\mathrm{i}}}{\partial {\mathrm{x}}_{\mathrm{j}}}\right)}^2\mathrm{dv}$$

where μ represents blood viscosity, i and j are arbitrary directions of the Cartesian axes and dv is the volume increment of the segmented lumen. Average and maximum EL inside the LV was calculated over one beat. Experienced physicians calculated EL values in duplicate using the VFM workstation, and the average of the results obtained was adopted as the EL value. Calculated EL values were analysed after being divided by stroke volume (SV) to adjust for the change in SV [L]: EL/SV [mW/m·L].

Definitions and outcome measures

HF was defined as the presence of HF‐related symptoms (dyspnoea, orthopnoea, or oedema) and at least one HF sign (peripheral oedema, ascites, pleural effusion, pulmonary vascular congestion, and an elevated serum natriuretic peptide level). ¹ , ² , ¹³ Pulmonary vascular congestion was confirmed by an estimated pulmonary‐capillary wedge pressure ≥35 mmHg in Doppler echocardiography. Elevated serum natriuretic peptide levels included a BNP level ≥400 pg/mL or NT‐proBNP level ≥1000 pg/mL. Non‐HF patients were defined as those with stable cardiovascular diseases and no evident HF. Decompensated HF was defined as an acute HF decompensation status to warrant hospitalization with oxygen inhalation and/or intravenous diuretics or inotropic support. A LV ejection fraction (EF) < 40% was regarded as reduced EF (HFrEF). In the clinical scenario (CS) classification of decompensated HF, CS 1 was defined as systolic blood pressure at admission ≥140 mmHg. ¹⁴

Outcome measures were average and maximum LV‐EL values divided by SV (mW/m·L).

Statistical analysis

Categorical variables are presented as numbers and percentages and compared by the chi‐square test or Fisher's exact test. Continuous variables are presented as means and standard deviations or medians with interquartile ranges and compared by the Student's t‐test or Wilcoxon rank sum test based on their distributions. The relationship between LV‐EL and NT‐proBNP and that between a change in LV‐EL and the door‐to‐record time under acute decompensated conditions were assessed by Pearson's correlation coefficients. The difference in EL between compensated and decompensated HF was assessed by the paired t‐test. Multivariable linear regression analyses were performed to identify independent risk factors for LV‐EL and higher LV‐EL under decompensated conditions than under compensated conditions.

All statistical analyses were performed using JMP 14 (SAS Institute Inc, Cary, NC) software and were two‐tailed. P values <0.05 and <0.10 were considered to be significant and marginally significant, respectively.

Results

Study population

The mean age of HF patients was 80.8 ± 12.7 years and the prevalence of both females and AF was 48.0% (Table  1 ). The prevalence of HFrEF was 34.0%. HF patients were characterized by a significantly older age, lower blood pressure, lower body weight, and significantly lower prevalence of hypertension than non‐HF patients. Renal and cardiac functions were also more impaired in HF patients.

Table 1.

Baseline characteristics of compensated HF and non‐HF patients

	Compensated HF (N = 50)	Non‐HF (N = 40)	P value	Decompensated HF (N = 50)	P value (vs. compensated HF)
Age (years)	80.8 ± 12.4	69.7 ± 8.1	<0.001	81.4 ± 10.7	‐
Female	24 (48.0%)	9 (22.5%)	0.01	24 (48.0%)	‐
Systolic blood pressure (mmHg)	108 (99–120)	124 (112–136)	0.001	123 (108–138)	<0.001
Clinical scenario 1 (≥140 mmHg)	‐	‐		12 (33.3%)
Diastolic blood pressure (mmHg)	66 (56–73)	76 (69–84)	<0.001	73 (62–81)	0.02
Heart rate (b.p.m.)	71 (63–81)	75 (66–87)	0.20	72 (63–89)	0.47
Body weight	52 (44–59)	68 (57–78)	<0.001	54 (47–64)	0.16
Atrial fibrillation	24 (48.0%)	27 (67.5%)	0.06	24 (48.0%)	‐
Persistent atrial fibrillation (at measurement)	20 (40.0%)	24 (60.0%)	0.06	22 (44.0%)	0.69
Hypertension	22 (44.0%)	30 (75.0%)	0.003	22 (44.0%)	‐
Diabetes mellitus	16 (32.0%)	8 (20.0%)	0.20	16 (32.0%)	‐
Dyslipidaemia	17 (34.0%)	17 (42.5%)	0.41	17 (34.0%)	‐
Chronic obstructive pulmonary disease	5 (10.0%)	1 (2.5%)	0.14	5 (10.0%)	‐
Ischaemic heart disease	19 (38.0%)	8 (20.0%)	0.04	19 (38.0%)	‐
p/s pacemaker implantation	13 (26.0%)	11 (27.5%)	0.87	13 (26.0%)	‐
Laboratory findings
Haemoglobin (g/dl)	11.8 (10.6–13.1)	13.8 (12.3–14.5)	<0.001	11.5 (10.2–12.6)	0.29
eGFR (mL/min/1.73 m2)	35.0 (21.5–45.0)	58.0 (49.6–67.0)	<0.001	36.0 (22.8–51.8)	0.50
NT‐proBNP (pg/mL)	3308 (990–1050)	552 (282–812)	<0.001	8103 (3236–14 798)	0.004
Echocardiography findings
Left ventricular end‐diastolic diameter (mm)	48.8 ± 8.4	46.7 ± 6.9	0.20	49.5 ± 8.1	0.68
Left ventricular ejection fraction (%)	48.6 ± 18.6	64.0 ± 9.9	<0.001	38.1 ± 18.6	0.006
<40%	17 (34.0%)	1 (2.5%)	<0.001	25 (50.0%)	0.10
Stroke volume (mL)	53.2 ± 21.5	63.7 ± 28.7	0.049	50.2 ± 17.8	0.45
E/A	5.4 ± 20.5	1.0 ± 0.4	0.35	10.6 ± 42.3	0.60
E/e′	20.1 ± 11.0	11.6 ± 4.4	<0.001	19.7 ± 9.5	0.89
Left atrial diameter (mm)	40.4 ± 6.2	39.4 ± 6.7	0.36	39.9 ± 7.1	0.69
Mitral regurgitation ≥grade 2	15 (32.0%)	2 (5.0%)	<0.001	21 (42.0%)	0.30
Tricuspid regurgitation ≥grade 2	14 (28.0%)	0 (0.0%)	<0.001	14 (30.0%)	0.83
Tricuspid regurgitation pressure gradient (mmHg)	28.1 ± 13.3	20.4 ± 5.4	0.004	34.3 ± 12.1	0.03
Medications
Ca channel blockers	22 (44.0%)	30 (75.0%)	0.003	22 (44.0%)	0.84
ACEi/ARB/ARNI	27 (54.0%)	18 (45.0%)	0.40	27 (54.0%)	1.00
Beta‐blockers	31 (62.0%)	17 (42.5%)	0.06	26 (52.0%)	0.31
SGLT2i	12 (24.0%)	2 (5.1%)	0.01	10 (20.0%)	0.63
Mineralocorticoid receptor antagonist	37 (74.0%)	2 (5.0%)	<0.001	31 (62.0%)	0.20
Oral diuretics	42 (84.0%)	4 (10.0%)	<0.001	41 (82.0%)	0.79
Oral anticoagulation	30 (60.0%)	26 (65.0%)	0.63	29 (58.0%)	0.84

Categorical variables are presented as numbers (percentage). Continuous variables are presented as means ± SD or medians with interquartile ranges.

ACEi, angiotensin‐converting enzyme inhibitors; ARB, angiotensin receptor blockers; ARNI, angiotensin receptor neprilysin inhibitors; Ca, calcium; eGFR, estimated glomerular filtration rate; HF, heart failure; NT‐proBNP, N‐terminal prohormone of brain natriuretic peptide; SGLT2i, sodium‐glucose cotransporter‐2 inhibitors.

The prevalence of decompensated HF classified into CS1 was 33.3%. Blood pressure and NT‐proBNP levels were significantly higher under acute decompensated conditions than under compensated conditions, while LV‐EF was significantly lower. Baseline characteristics between HFrEF and non‐HFrEF were described in Table S1. Non‐HFrEF patients had significantly higher blood pressure and SV than HFrEF patients.

Intracardiac energy inefficiency between heart failure and non‐heart failure

Average LV‐EL was significantly higher in compensated HF patients than in non‐HF patients (40 mW/m·L vs. 26 mW/m·L, P = 0.047) (Figure  2 ). Similarly, maximum LV‐EL was significantly higher in compensated HF patients (140 mW/m·L vs. 73 mW/m·L, P = 0.007). In the sensitivity analysis, significantly higher LV‐EL in compensated HF patients was pronounced in patients with AF or hypertension (Table S2). On the other hand, the relationship between LV‐EL and serum NT‐proBNP levels was weak regardless of the presence of HF (Figure S1). The multivariable analysis identified age and systolic blood pressure as independent risk factors for high average LV‐EL, and age and LVEF as risk factors for high maximum LV‐EL (Table  2 ). Chronic obstructive pulmonary disease was a unique risk factor for both low average and maximum LV‐EL.

Figure 2.

Left ventricular energy loss in HF and non‐HF patients. EL, energy loss; HF, heart failure.

Table 2.

Risk factors for left ventricular energy loss

Variables	Univariate analysis			Multivariable analysis
	β	95% CI	P value	β	95% CI	P value
(A) Average energy loss
Presence of heart failure	2.3	1.4 to 6.0	0.22	2.7	3.2 to 8.7	0.36
Age (years)	0.4	0.1 to 0.7	0.006	0.5	−0.07 to 1.0	0.03
Female	1.3	−2.5 to 5.2	0.50	2.6	−2.0 to 7.2	0.26
Systolic blood pressure (mmHg)	0.2	−0.04 to 0.4	0.10	0.3	0.01 to 0.5	0.04
Heart rate (b.p.m.)	−0.01	−0.2 to 0.1	0.89	−0.03	−0.2 to 0.1	0.75
Body weight (kg)	−0.2	−0.4 to 0.09	0.20	0.3	−0.2 to 0.7	0.25
Chronic obstructive pulmonary disease	−11.3	−18.5 to −4.2	0.002	−11.0	−18.8 to −3.3	0.006
Haemoglobin (g/dL)	−2.8	−4.6 to 1.0	0.003	−1.7	−4.2 to 0.8	0.18
eGFR (mL/min/1.73 m2)	−0.08	−0.3 to 0.1	0.42	0.2	−0.02 to 0.5	0.07
NT‐proBNP (pg/mL)	0.0002	−0.0003 to 0.0006	0.65	0.0008	−0.0007 to 0.0005	0.81
Left ventricular end‐diastolic diameter (mm)	0.1	−0.4 to 0.6	0.64	0.4	−0.3 to 1.1	0.28
Left ventricular ejection fraction (%)	0.03	−0.2 to 0.3	0.78	0.1	−0.3 to 0.5	0.55
Left atrial diameter (mm)	0.3	−0.2 to 1.0	0.18	0.4	−0.5 to 1.1	0.29
(B) Maximum energy loss
Presence of heart failure	8.6	2.3 to 19.4	0.12	12.9	3.3 to 29.0	0.12
Age (years)	1.3	0.5 to 2.2	0.003	1.4	−0.2 to 2.7	0.03
Female	3.1	−8.2 to 14.4	0.59	9.5	−3.0 to 22.0	0.13
Systolic blood pressure (mmHg)	0.2	−0.5 to 0.9	0.54	0.4	−0.3 to 1.1	0.39
Heart rate (b.p.m.)	−0.2	−0.7 to 0.2	0.36	−0.1	−0.6 to 0.3	0.54
Body weight (kg)	−0.6	−1.4 to 0.08	0.08	0.5	−0.7 to 1.7	0.43
Chronic obstructive pulmonary disease	−34.4	−55.1 to −13.8	0.001	−33.8	−54.8 to −12.8	0.002
Haemoglobin (g/dL)	−8.1	−13.2 to 2.9	0.003	−4.7	−11.5 to 2.0	0.17
eGFR (mL/min/1.73 m2)	−0.2	−0.7 to 0.4	0.59	0.7	−0.03 to 1.4	0.06
NT‐proBNP (pg/mL)	0.0001	−0.0002 to 0.0001	0.84	0.0004	−0.0002 to 0.0001	0.60
Left ventricular end‐diastolic diameter (mm)	0.4	−1.0 to 1.2	0.54	1.5	−0.3 to 3.4	0.11
Left ventricular ejection fraction (%)	0.3	−0.4 to 0.9	0.39	1.0	0.07 to 2.0	0.04
Left atrial diameter (mm)	1.6	−0.06 to 3.3	0.06	1.9	−0.04 to 3.9	0.06

CI, confidence interval; eGFR, estimated glomerular filtration rate; HF, heart failure; HR, hazard ratio; NT‐proBNP, N‐terminal prohormone brain natriuretic peptide.

Intracardiac energy inefficiency between decompensated and compensated heart failure conditions

The median door‐to‐record time at admission for acute decompensated HF was 5.5 (2.0–12.3) hours. The interval of the measurement dates between decompensated and compensated conditions was 8.0 (6.0–9.5) days. Average LV‐EL was significantly higher under decompensated conditions than under compensated conditions (55 mE/m·L vs. 40 mE/m·L, [+18 mE/m·L, P = 0.03]) (Figure 3 A ). Similarly, maximum LV‐EL was significantly higher in HF patients under compensated conditions (140 mW/m·L vs. 160 mW/m·L, [+26 mE/m·L, P < 0.001]). Changes in LV‐EL under compensated and decompensated HF conditions showed a weak inverse correlation with the door‐to‐record time (R = 0.29, P = 0.04) (Figure 2).

Figure 3.

Changes in average left ventricular energy loss between compensated and decompensated conditions. A) Overall, B) according to the ejection fraction, and C) according to the clinical scenario classification. CS, clinical scenario; EF, ejection fraction; EL, energy loss; HFrEF, heart failure with a reduced ejection fraction.

The higher average LV‐EL under acute decompensated HF conditions than under compensated HF conditions was significant in HF with non‐HFrEF (≥40%) (+19 mW/m·L, P = 0.009), but not in HFrEF (<40%) (+4 mW/m·L, P = 0.74) (Figure 3 ‐B). The higher average LV‐EL under decompensated HF conditions than under compensated HF conditions was significant in HF of CS1 (+23 mW/m·L, P = 0.008), but not in HF of non‐CS1 (+11 mW/m·L, P = 0.34) (Figure 3 ‐C). Under acute decompensated HF conditions, the difference in average LV‐EL between HF of CS1 and HF of non‐CS1 was marginally significant (64 mE/m·L vs. 49 mE/m·L, P = 0.10). The greater increase in LV‐EL under decompensated conditions in non‐HFrEF and CS1 of HF was also observed for the maximum value of LV‐EL (Figure S3). The multivariable analysis identified the estimated glomerular filtration rate as a risk factor for a decrease in average LV‐EL under decompensated conditions. However, there were no independent risk factors for a decrease in maximum LV‐EL (Table  3 ).

Table 3.

Risk factors for an increase in left ventricular energy loss under decompensated conditions

Variables	Univariate analysis			Multivariable analysis
	β	95% CI	P value	β	95% CI	P value
(A) Average energy loss
Age (years)	−0.2	−1.0 to 0.7	0.21	−1.1	−2.3 to 0.1	0.08
Female	3.3	−7.3 to 13.8	0.54	−4.4	−17.8 to 9.0	0.51
Systolic blood pressure (mmHg)	0.6	0.03 to 1.3	0.04	0.4	−0.4 to 1.2	0.32
Heart rate (b.p.m.)	−0.002	−0.7 to 0.7	0.99	0.1	−0.6 to 0.9	0.71
Body weight (kg)	−0.2	−1.2 to 0.7	0.63	−0.5	−1.9 to 0.9	0.46
Chronic obstructive pulmonary disease	3.6	−14.1 to −21.2	0.69	8.2	−10.2 to 26.6	0.37
Haemoglobin (g/dL)	2.1	−3.2 to 7.4	0.43	1.9	−5.6 to 9.4	0.60
eGFR (mL/min/1.73 m2)	−0.6	−1.1 to 0.03	0.04	−0.7	−1.4 to −0.01	0.047
NT‐proBNP (pg/mL)	0.0008	−0.0001 to 0.0001	0.89	0.0004	−0.0001 to 0.0002	0.61
Left ventricular end‐diastolic diameter (mm)	−1.5	−2.7 to 0.3	0.02	−1.1	−3.5 to 1.3	0.37
Left ventricular ejection fraction (%)	0.6	0.02 to 1.1	0.04	−0.01	−1.0 to 1.0	0.98
Left atrial diameter (mm)	−0.7	−2.5 to 1.0	0.41	0.2	−2.0 to 2.3	0.87
(B) Maximum energy loss
Age (years)	−0.3	−2.8 to 2.2	0.84	−2.3	−5.6 to 1.1	0.18
Female	18.1	−12.3 to 48.5	0.24	−6.0	−43.5 to 31.5	0.75
Systolic blood pressure (mmHg)	1.7	−0.09 to 3.5	0.06	0.9	−1.3 to 3.1	0.43
Heart rate (b.p.m.)	−0.6	−2.7 to 1.5	0.57	−0.4	−2.5 to 1.7	0.69
Body weight (kg)	−1.6	−4.4 to 1.3	0.28	−1.7	−5.5 to 2.2	0.38
Chronic obstructive pulmonary disease	−13.8	−65.0 to 37.4	0.54	−3.9	−55.5 to −47.7	0.88
Haemoglobin (g/dl)	−5.0	−9.1 to 20.2	0.45	8.5	−12.6 to 29.5	0.42
eGFR (mL/min/1.73 m2)	−1.7	−3.1 to 0.2	0.03	−1.8	−3.8 to 0.2	0.07
NT‐proBNP (pg/mL)	0.0008	−0.0002 to 0.0004	0.56	0.0008	−0.0003 to 0.0005	0.69
Left ventricular end‐diastolic diameter (mm)	−3.8	−7.3 to 0.2	0.04	−4.2	−10.9 to 2.6	0.22
Left ventricular ejection fraction (%)	0.6	−1.0 to 2.3	0.45	−1.5	−4.4 to 1.3	0.29
Left atrial diameter (mm)	−1.5	−6.6 to 3.6	0.55	1.5	−4.5 to 7.4	0.62

CI, confidence interval; eGFR, estimated glomerular filtration rate; HR, hazard ratio; NT‐proBNP, N‐terminal prohormone brain natriuretic peptide.

Discussion

The main results of the present study are that LV‐EL was higher in stable compensated HF patients than in non‐HF patients and significant under acute decompensated conditions, particularly in HF with preserved EF and CS1.

Echo‐VFM is a novel technology for visualizing flow velocity vectors and observing intracardiac dynamics from viscous dissipation in turbulent blood flow, calculated as EL. ¹⁰ , ¹¹ Regarding echo‐VFM for HF patients, previous studies reported high intracardiac EL in patients with severe aortic regurgitation or LV function, which was improved by cardiac resynchronization therapy implantation. ¹⁵ , ¹⁶ We also previously demonstrated that high EL in both the LV and atrium during AF was associated with the presence of HF. ¹² Sinus restoration improved intracardiac energy inefficiency in AF patients with HF. These findings suggest that intracardiac energy inefficiency plays an important role in HF, which has not yet been systematically evaluated. In the present study, we evaluated intracardiac energy inefficiency, measured by LV‐EL using echo‐VFM, in HF patients, and intracardiac energy inefficiency was more apparent in stable compensated HF patients than in non‐HF patients, potentially posing a risk for acute decompensation in HF patients. The difference in LV‐intracardiac energy inefficiency between patients with and without HF is significant in cases of AF, suggesting that AF cases with concomitant HF are at a higher risk of subsequent acute decompensation. Chronic obstructive pulmonary disease, which is a known risk factor for HF, ¹⁰ , ¹⁷ has been associated with low LV‐EL regardless of the presence of HF. Right heart dysfunction may mitigate intracardiac energy inefficiency in LV. However, we were unable to fully evaluate right heart dysfunction in the present study. Further studies that examine the relationship between right ventricular function and intracardiac energy inefficiency are needed.

We also observed a larger increase in LV‐EL in HF patients under acute decompensated conditions, suggesting that intracardiac inefficacy in HF patients worsens during acute decompensation. Although various pathological conditions have been reported in acute HF decompensation, this is the first study to report that intracardiac inefficacy is one of the pathologies associated with acute decompensation. Intracardiac inefficacy appears to play a role in the pathogenesis of acute decompensation of CS1 (blood pressure ≥140 mmHg). HF of CS1 is considered to occur due to afterload mismatch caused by an increase in blood pressure, resulting in the abnormal distribution of body fluids. ¹⁴ Clinically, it may also lead to an abrupt exacerbation due to increased sympathetic nervous system activity. The present results suggest that the worsening of intracardiac inefficacy due to an increased afterload further accelerate acute decompensation. Additionally, intracardiac inefficacy was pronounced during acute decompensation in non‐HFrEF patients. One of the cardiac characteristic of HF with preserved EF (HFpEF) is impaired ventricular diastolic function without systolic dysfunction, and acute decompensation primarily due to diastolic dysfunction may induce intracardiac inefficacy. ¹⁸ , ¹⁹ On the other hand, HFpEF is a heterogeneous disease concept that includes various pathologies, such as atrial dysfunction, and may even occur under non‐cardiac conditions, including obesity and lung disease. ¹⁹ , ²⁰ Because a detailed analysis was limited by the small number of patients with HFpEF in the present study, further studies that examine intracardiac inefficacy in each HFpEF phenotype are warranted.

Study limitations

The present study had several limitations. This is the first study to focus on intracardiac energy inefficiency in HF patients under compensated and decompensated conditions; however, the number of patients enrolled was small and the follow‐up duration was short. The patients examined were all Japanese also and were slightly older and had a lower body weight than HF cohorts in other countries. ²¹ In addition, there was a delay in measuring echo‐VFM after an emergent visit for the acute decompensation of HF in some patients who had been already received the initial treatment for HF at the time of the measurement. In these cases, the potential difference in intracardiac energy inefficiency between decompensated and compensated HF conditions may have been underestimated. Another limitation is that we did not perform all conventional echocardiographic evaluations, such as right ventricular function and strain, which may have hindered the generalization of EL assessed by novel echo‐VFM.

Conclusions

Energy inefficiency, assessed using echo‐VFM, in LV was apparent even in stable compensated HF patients and significant under acute decompensated conditions, particularly in HFpEF and CS1.

Conflict of interest

None declared.

Supporting information

Table S1: Baseline characteristics of HFrEF and non‐HFrEF patients.

Table S2: Energy loss in compensated HF and non‐HF patient subgroups.

Figure S1: Relationship between left ventricular energy loss and serum NT‐proBNP levels.

Figure S2: Relationship between changes in left ventricular energy loss and door‐to‐record times at admission for acute decompensated HF.

Figure S3: Changes in maximum left ventricular energy loss under compensated and decompensated HF conditions.

Kawaji, T. , Kaneda, K. , Yaku, H. , Bao, B. , Hojo, S. , Tezuka, Y. , Matsuda, S. , Shiomi, H. , Kato, M. , Yokomatsu, T. , Miki, S. , and Ono, K. (2025) Intracardiac energy inefficiency during decompensated and compensated heart failure. ESC Heart Failure, 12: 101–109. 10.1002/ehf2.15034.

Data availability statement

All relevant data are within the manuscript.