Cardiol Res

Cardiology Research, ISSN 1923-2829 print, 1923-2837 online, Open Access

Article copyright, the authors; Journal compilation copyright, Cardiol Res and Elmer Press Inc

Journal website https://www.cardiologyres.org

Original Article

Volume 14, Number 3, June 2023, pages 201-210

Differentiating Characteristics and Responses to Treatment of New-Onset Heart Failure With Preserved and Reduced Ejection Fraction in Ambulatory Patients

Figure 1. The flow diagram of the patients. All patients with new-onset heart failure (HF) were included in the study. The clinical characteristics and findings of electrocardiography (ECG) and echocardiography were recorded. Patients were diagnosed with HF preserved ejection fraction (HFpEF) or HF with reduced EF (HFrEF) and started medical therapy. They were followed up once weekly, and medications were titrated according to clinical status. The response to medical therapy was evaluated on the basis of resolution of HF in 30 days.

Figure 2. t-test comparison of the rate of resolution of heart failure (HF) in 30 days according to EF (n = 123 patients). HFpEF: heart failure with preserved ejection fraction; HFrEF: heart failure with reduced ejection fraction.

**Table 1.** Echocardiographic Findings of the Cohort (N = 146)
Variable	HFpEF (n = 68)	HFrEF (n = 78)	P value
HFpEF: heart failure with preserved ejection fraction; HFrEF: heart failure with reduced ejection fraction; LVEF: left ventricle ejection fraction; LVEDD: left ventricular end-diastolic diameter; LVESD: left ventricle end-systolic diameter; LV: left ventricle; RWA: regional wall motion abnormalities; MR: mitral regurgitation; AS: aortic stenosis; AR: aortic regurgitation.
LVEF (mean)	57.7 ± 6.4	33.2 ± 8.2	< 0.001
LVEDD (mm)	50.0 ± 6.3	58.9 ± 9.6	0.007
LVESD (mm)	37.7 ± 8.3	52.4 ± 9.4	0.004
LV mass (g)	279.4 ± 69.7	243.7 ± 79.4	0.15
RWA (%)	12.7%	37.8%	0.03
E/A ratio	1.1 ± 0.62	1.18 ± 0.81	0.93
Severe MR (%)	3.5	19.4	< 0.001
Severe AS (%)	1.3	3.2	0.042
Severe AR (%)	1.1	0.5	0.056

Table 1. Echocardiographic Findings of the Cohort (N = 146)

Variable

HFpEF (n = 68)

HFrEF (n = 78)

P value

HFpEF: heart failure with preserved ejection fraction; HFrEF: heart failure with reduced ejection fraction; LVEF: left ventricle ejection fraction; LVEDD: left ventricular end-diastolic diameter; LVESD: left ventricle end-systolic diameter; LV: left ventricle; RWA: regional wall motion abnormalities; MR: mitral regurgitation; AS: aortic stenosis; AR: aortic regurgitation.

LVEF (mean)

57.7 ± 6.4

33.2 ± 8.2

< 0.001

LVEDD (mm)

50.0 ± 6.3

58.9 ± 9.6

0.007

LVESD (mm)

37.7 ± 8.3

52.4 ± 9.4

0.004

LV mass (g)

279.4 ± 69.7

243.7 ± 79.4

0.15

RWA (%)

12.7%

37.8%

0.03

E/A ratio

1.1 ± 0.62

1.18 ± 0.81

0.93

Severe MR (%)

3.5

19.4

< 0.001

Severe AS (%)

1.3

3.2

0.042

Severe AR (%)

1.1

0.5

0.056

**Table 2.** Univariate and Multivariate Adjusted Logistic Regression Analyses of Comorbidities in Patients With HFpEF and HFrEF
	Univariate	Multivariate
Age	62.12 ± 11.55	66.99 ± 11.19	1.8 (0.9 - 2.5)	0.008
Male	35.3	38.5	0.87 (0.44 - 1.71)	0.693
Post hoc sample calculation revealed sufficient power for performing logistic regression modelling (R² = 0.324, predictors = 7, P ≤ 0.05; observed statistical power = 0.99). BMI: body mass index; CAD: coronary artery diseases; DM: diabetes mellitus; CKD: chronic kidney disease; AF: atrial fibrillation; VHD: valvular heart disease; CVA: cerebrovascular accident; HFpEF: heart failure with preserved ejection fraction; HfrEF: heart failure with reduced ejection fraction; OR: odds ratio; CI: confidence interval; SD: standard deviation.
Hyperlipidemia	23.5	19.2	0.98 (0.93 - 1.04)	0.61
Hypertension	70.6	60.3	1.8 (1.2 - 4.3)	0.26
BMI	32.05 ± 4.41	30.23 ± 4.98	3.1 (1.7 - 3.4)	0.022	2.8 (1.8 - 3.2)	0.07
CAD	22.1	39.7	2.33 (1.12 - 2.84)	0.022	3.52 (1.46 - 4.52)	0.005
DM	48.5	53.8	2.33 (1.12 - 4.84)	0.43
CKD	1.5	14.1	1.2 (0.4 - 3.2)	0.006	10.2 (4.3 - 14.6)	0.07
VHD	7.4	25.6	4.35 (2.53 - 5.33)	0.003	6.93 (4.04 - 8.54)	0.002
AF	8.8	20.5	2.67 (1 - 3.26)	0.04	2.48 (1.76 - 4.12)	0.013
CVA	5.9	7.7	1.3 (0.7 - 5.6)	0.22

Table 2. Univariate and Multivariate Adjusted Logistic Regression Analyses of Comorbidities in Patients With HFpEF and HFrEF

Univariate

Multivariate

HFpEF, % or mean ± SD

HFrEF, % or mean ± SD

OR (95% CI)

P value

OR (95% CI)

P value

Age

62.12 ± 11.55

66.99 ± 11.19

1.8 (0.9 - 2.5)

0.008

Male

35.3

38.5

0.87 (0.44 - 1.71)

0.693

Comorbidities

Post hoc sample calculation revealed sufficient power for performing logistic regression modelling (R² = 0.324, predictors = 7, P ≤ 0.05; observed statistical power = 0.99). BMI: body mass index; CAD: coronary artery diseases; DM: diabetes mellitus; CKD: chronic kidney disease; AF: atrial fibrillation; VHD: valvular heart disease; CVA: cerebrovascular accident; HFpEF: heart failure with preserved ejection fraction; HfrEF: heart failure with reduced ejection fraction; OR: odds ratio; CI: confidence interval; SD: standard deviation.

Hyperlipidemia

23.5

19.2

0.98 (0.93 - 1.04)

0.61

Hypertension

70.6

60.3

1.8 (1.2 - 4.3)

0.26

BMI

32.05 ± 4.41

30.23 ± 4.98

3.1 (1.7 - 3.4)

0.022

2.8 (1.8 - 3.2)

0.07

CAD

22.1

39.7

2.33 (1.12 - 2.84)

0.022

3.52 (1.46 - 4.52)

0.005

48.5

53.8

2.33 (1.12 - 4.84)

0.43

CKD

1.5

14.1

1.2 (0.4 - 3.2)

0.006

10.2 (4.3 - 14.6)

0.07

VHD

7.4

25.6

4.35 (2.53 - 5.33)

0.003

6.93 (4.04 - 8.54)

0.002

8.8

20.5

2.67 (1 - 3.26)

0.04

2.48 (1.76 - 4.12)

0.013

CVA

5.9

7.7

1.3 (0.7 - 5.6)

0.22

**Table 3.** Univariate and multivariate adjusted logistic regression analyses of clinical presentation in patients with HFpEF and HFrEF
	Univariate	Multivariate
Post hoc sample calculation revealed sufficient power for performing logistic regression modelling (R² = 0.471, predictors = 8, P ≤ 0.05; observed statistical power = 1.0). NYHA: New York Heart Association classification of dyspnea; PND: paroxysmal nocturnal dyspnea; LL edema: lower limb edema; Low COP: low cardiac output symptoms; HFpEF: heart failure with preserved ejection fraction; HFrEF: heart failure with reduced ejection fraction; OR: odds ratio; CI: confidence interval.
NYHA 1 - 2	86.8	51.3	9.3 (7.6 - 15.3)	< 0.001	5.4 (1.4 - 7.3)	0.08
NYHA 3 - 4	5.9	33.3	8 (2.63 - 9.38)	< 0.001	4.3 (2.1 - 8.3)	0.092
Orthopnea	11.8	41	5.22 (2.2 - 6.39)	< 0.001	4.2 (1.3 - 7.2)	0.21
PND	5.9	33.3	8 (2.63 - 10.3)	< 0.001	5.3 (1.3 - 7.2)	0.33
Angina	14.7	20.5	1.6 (0.6 - 5.7)	0.21
LL edema	38.2	37.2	1.3 (1.1 - 6.2)	0.33
Low COP	1.5	14.1	11 (10.38 - 13.6)	0.006	8.3 (2.1 - 16.5)	0.12

Table 3. Univariate and multivariate adjusted logistic regression analyses of clinical presentation in patients with HFpEF and HFrEF

Univariate

Multivariate

HFpEF (%)

HFrEF (%)

OR (95% CI)

P value

OR (95% CI)

P value

Post hoc sample calculation revealed sufficient power for performing logistic regression modelling (R² = 0.471, predictors = 8, P ≤ 0.05; observed statistical power = 1.0). NYHA: New York Heart Association classification of dyspnea; PND: paroxysmal nocturnal dyspnea; LL edema: lower limb edema; Low COP: low cardiac output symptoms; HFpEF: heart failure with preserved ejection fraction; HFrEF: heart failure with reduced ejection fraction; OR: odds ratio; CI: confidence interval.

NYHA 1 - 2

86.8

51.3

9.3 (7.6 - 15.3)

< 0.001

5.4 (1.4 - 7.3)

0.08

NYHA 3 - 4

5.9

33.3

8 (2.63 - 9.38)

< 0.001

4.3 (2.1 - 8.3)

0.092

Orthopnea

11.8

5.22 (2.2 - 6.39)

< 0.001

4.2 (1.3 - 7.2)

0.21

PND

5.9

33.3

8 (2.63 - 10.3)

< 0.001

5.3 (1.3 - 7.2)

0.33

Angina

14.7

20.5

1.6 (0.6 - 5.7)

0.21

LL edema

38.2

37.2

1.3 (1.1 - 6.2)

0.33

Low COP

1.5

14.1

11 (10.38 - 13.6)

0.006

8.3 (2.1 - 16.5)

0.12

**Table 4.** Univariate and Multivariate Adjusted Logistic Regression Analyses of ECG Findings in Patients With HFpEF and HFrEF
	Univariate	Multivariate
Post hoc sample calculation revealed sufficient power for performing logistic regression modelling (R² = 0.497, predictors = 4, P ≤ 0.05; observed statistical power =1.0). LVH: left ventricular hypertrophy; LBBB: left bundle branch block; RBBB: right bundle branch block; AF: atrial fibrillation; HFpEF: heart failure with preserved ejection fraction; HFrEF: heart failure with reduced ejection fraction; OR: odds ratio; CI: confidence interval.
Normal	69.1	9	2.6 (1.2 - 5.8)	< 0.001	3.6 (1.4 - 7.7)	< 0.001
Ischemic changes	11.8	20.5	7.3 (2.1 - 15.3)	0.12
LVH	2.9	1.3	0.9 (0.2 - 3.6)	0.21
LBBB	0	19.2	9.8 (8.2 - 10.2)	< 0.001	11.3 (8.2 - 12.3)	< 0.001
RBBB	1.5	3.8	2.1 (0.6 - 8.2)	0.42
AF	5.9	20.5	4.13(3.1 - 6.4)	0.01	2.6 (1.4 - 4.2)	0.07

Table 4. Univariate and Multivariate Adjusted Logistic Regression Analyses of ECG Findings in Patients With HFpEF and HFrEF

Univariate

Multivariate

HFpEF (%)

HFrEF (%)

OR (95% CI)

P value

OR (95% CI)

P value

Post hoc sample calculation revealed sufficient power for performing logistic regression modelling (R² = 0.497, predictors = 4, P ≤ 0.05; observed statistical power =1.0). LVH: left ventricular hypertrophy; LBBB: left bundle branch block; RBBB: right bundle branch block; AF: atrial fibrillation; HFpEF: heart failure with preserved ejection fraction; HFrEF: heart failure with reduced ejection fraction; OR: odds ratio; CI: confidence interval.

Normal

69.1

2.6 (1.2 - 5.8)

< 0.001

3.6 (1.4 - 7.7)

< 0.001

Ischemic changes

11.8

20.5

7.3 (2.1 - 15.3)

0.12

LVH

2.9

1.3

0.9 (0.2 - 3.6)

0.21

LBBB

19.2

9.8 (8.2 - 10.2)

< 0.001

11.3 (8.2 - 12.3)

< 0.001

RBBB

1.5

3.8

2.1 (0.6 - 8.2)

0.42

5.9

20.5

4.13(3.1 - 6.4)

0.01

2.6 (1.4 - 4.2)

0.07

**Table 5.** Univariate and Multivariate Adjusted Logistic Regression Analyses of the Etiology of HFpEF and HFrEF, as Well as the Diagnostic Methods
	Univariate	Multivariate	Method
Post hoc sample calculation revealed sufficient power for performing logistic regression modelling (R² = 0.564, predictors = 6, P ≤ 0.05; observed statistical power = 1.0). HTN: hypertension; CAD: coronary artery disease; VHD: valvular heart disease; DCM: dilated cardiomyopathy; 24-h ABP: 24-hour ambulatory blood pressure monitoring; ECG: electrocardiography; HFpEF: heart failure with preserved ejection fraction; HFrEF: heart failure with reduced ejection fraction; OR: odds ratio; CI: confidence interval.
Undiagnosed HTN	22.1	2.6	1.8 (1.1 - 4.3)	< 0.001	2 (1.8 - 3.8)	0.002	24-h ABP monitoring
Uncontrolled HTN	52.9	9	2.4 (1.9 - 3.8)	< 0.001	3.6 (2.3 - 5.7)	< 0.001	Home and clinical BP monitoring
VHD	5.9	23.1	4.8 (3.54 - 6.8)	< 0.001	3.4 (2.3 - 6.1)	0.004	Severe VHD in echocardiography
CAD	1.5	30.8	29.78 (26.3 - 35.2)	< 0.001	2.43 (1.59 - 4.05)	0.022	Medical records, ECG and echocardiography
DCM	0	16.7	45 (42 - 52)	< 0.001	26.3 (24.4 - 27.2)	< 0.001	Echocardiography

Table 5. Univariate and Multivariate Adjusted Logistic Regression Analyses of the Etiology of HFpEF and HFrEF, as Well as the Diagnostic Methods

Univariate

Multivariate

Method

HFpEF (%)

HFrEF (%)

OR (95% CI)

P value

OR (95% CI)

P value

Post hoc sample calculation revealed sufficient power for performing logistic regression modelling (R² = 0.564, predictors = 6, P ≤ 0.05; observed statistical power = 1.0). HTN: hypertension; CAD: coronary artery disease; VHD: valvular heart disease; DCM: dilated cardiomyopathy; 24-h ABP: 24-hour ambulatory blood pressure monitoring; ECG: electrocardiography; HFpEF: heart failure with preserved ejection fraction; HFrEF: heart failure with reduced ejection fraction; OR: odds ratio; CI: confidence interval.

Undiagnosed HTN

22.1

2.6

1.8 (1.1 - 4.3)

< 0.001

2 (1.8 - 3.8)

0.002

24-h ABP monitoring

Uncontrolled HTN

52.9

2.4 (1.9 - 3.8)

< 0.001

3.6 (2.3 - 5.7)

< 0.001

Home and clinical BP monitoring

VHD

5.9

23.1

4.8 (3.54 - 6.8)

< 0.001

3.4 (2.3 - 6.1)

0.004

Severe VHD in echocardiography

CAD

1.5

30.8

29.78 (26.3 - 35.2)

< 0.001

2.43 (1.59 - 4.05)

0.022

Medical records, ECG and echocardiography

DCM

16.7

45 (42 - 52)

< 0.001

26.3 (24.4 - 27.2)

< 0.001

Echocardiography

**Table 6.** Comparison of Medications Used for Patients With Heart Failure With Preserved Ejection Fraction (HFpEF) and Heart Failure With Reduced Ejection Fraction (HFrEF)
	HFpEF (%)	HFrEF (%)	P value
ARNI: angiotensin receptor-neprilysin inhibitors; ACEI: angiotensin converting enzyme inhibitors; ARB: angiotensin receptor blocker; DOAC: direct-acting oral anticoagulant; HFpEF: heart failure with preserved ejection fraction; HFrEF: heart failure with reduced ejection fraction.
ARNI	0.0	86.6	< 0.001
ACEI/ARB	96.4	11.2	0.007
Spironolactone	8.3	89.7	< 0.001
Furosemide	84.7	89.2	0.47
Beta-blocker	48.5	12.8	0.016
Antiplatelet	92.4	84.4	0.41
Statin	96.7	98.4	0.52
DOAC	3.9	15.6	0.003
Nitrate	10.7	13.8	0.32
Hydralazine	1.8	2.2	0.22

Table 6. Comparison of Medications Used for Patients With Heart Failure With Preserved Ejection Fraction (HFpEF) and Heart Failure With Reduced Ejection Fraction (HFrEF)

HFpEF (%)

HFrEF (%)

P value

ARNI: angiotensin receptor-neprilysin inhibitors; ACEI: angiotensin converting enzyme inhibitors; ARB: angiotensin receptor blocker; DOAC: direct-acting oral anticoagulant; HFpEF: heart failure with preserved ejection fraction; HFrEF: heart failure with reduced ejection fraction.

ARNI

0.0

86.6

< 0.001

ACEI/ARB

96.4

11.2

0.007

Spironolactone

8.3

89.7

< 0.001

Furosemide

84.7

89.2

0.47

Beta-blocker

48.5

12.8

0.016

Antiplatelet

92.4

84.4

0.41

Statin

96.7

98.4

0.52

DOAC

3.9

15.6

0.003

Nitrate

10.7

13.8

0.32

Hydralazine

1.8

2.2

0.22